Current Pharmaceutical Design - Volume 16, Issue 7, 2010

Part II of the above mentioned hot topic will focus on the pathogenesis of cardiovascular events; the molecular bases of longevity, and diet and ageing. Panaro and associates [1], Panaro and associates [2], Nicita-Mauro and associates [3], Forte and associates [4], Licastro and associates [5] and Bennati and associates [6] will point out the molecular bases for the cardiovascular risk, even including infections, smoking and metabolic syndrome. Singh and associates [7] and Cevenini and associates [8] will emphasize the role of HSP 70 as well as innovative anti-ageing targets to favor longevity, respectively. De Lorenzo and associates [9], Russo and associates [10], Barbagallo and Dominguez [11], Carbonelli and associates [12], Linsalata and associates [13], Amati and associates [14], Jirillo and associates [15], Amati and associates [16], Jirillo and associates [17], Calabrese and associates [18], Sikora and associates [19], and Amati and associates [20] will point out the major dietary approaches to prevent ageing or ameliorate its status by means of several types of nutraceuticals endowed with antioxidant and/or immunomodulating properties. >

This study is focused on the links between the major products of inflammation and cell damage induced by the administration of lipopolysaccharide (LPS) from Salmonella typhimurium in embryonal cardiomyocytes. LPS treatment for 72 hours induced transcription factor NF-κB activation, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression, nitric oxide (NO) and tumor necrosis factor (TNF)-α release. Moreover, LPS administration induced a significant cell loss, reversed by the NO-synthases inhibitor, suggesting a relationship between cell damage and iNOS-dependent NO overproduction. Cell death was reversed by the specific NF-κB inhibitor, TPCK, whereas COX-2 specific inhibitor determined an increase of cell damage in terms of apoptosis, as observed by YO-PRO immunostaining, DNA laddering analysis and caspase-3 activation. Overall these findings evidenced a selective role for NF-κB in mediating NO-induced cell damage and a protective action by COX-2 in LPS-treated embryonal cardiomyocytes. The reflection of these experiments on human cardiac pathology will be discussed.

Lipopolysaccharide (LPS) the major structural component of the outer membrane of Gram-negative bacteria contributes to the cardiovascular collapse and death observed in septic patients, as well as in the immunocompromised host. LPS activates multiple cells to release proinflammatory cytokines, nitric oxide (NO) and other reactive molecules able to depress cardiac functions. It has been appreciated that the pattern recognition receptor, TLR4, is a signalling receptor for LPS, but its role in the embryonal cardiomyocytes is poorly understood. Here, we provide evidence for TLR4-dependent functional responses by LPS treated embryonal cardiomyocytes. It will be reported that LPS is able to induce TNF-α and NO release from cultured cardiomyocytes, while molecular and morphological evidence demonstrates the expression of TLR4 on surface membrane of embryonal cardiomyocytes. LPS-induced signalling was studied evaluating the expression of the extracellular signal-regulated kinase (ERK) and signal transducer and activators of transcription (STAT) protein families in response to LPS. The role of TLR4 was investigated with blocking assays using monoclonal antibody against this endotoxin receptor. Our results indicated that LPS-induced activation of signal transduction in embryonal cardiomyocytes occurs by a TLR4-dependent mechanism. In summary, chick embryonal cardiomyocytes may constitute a valid experimental model in order to study the LPS induced inflammatory responses by cardiomyocytes, useful not only to identify the signalling pathways evoked by endotoxin receptor, including TLR4, but also to suggest therapeutic targets for the control of myocardial dysfunction induced by infectious agents. In this respect, in elderly a continuous leakage of LPS from gut flora and/or external environment should be regarded as a possible cause of cardiac failure and, therefore, adequately prevented or treated.

The smoke of cigarettes represents an important accelerator of the aging process, and there is no doubt that smoke is an important risk factor for many diseases, in particular for cardiovascular, neoplastic and respiratory diseases. Smoking plays an important role also in the development of other pathological conditions being particularly frequent in geriatric ages, such as dementia, osteoporosis, diabetes, erectile dysfunction, senile macular degeneration, nuclear cataract and alterations of skin. This means that smoke compromises not only life expectancy, but also the quality of the life, favoring the occurrence of non-autonomy. Non-smokers have a much higher life expectancy than smokers, and the suspension of smoking is accompanied, even in the elderly, by an increase in the survival time due to the reduction of smoke-induced biological damage. The first requirement of stopping smoking certainly is the motivation of the smoker himself to do this, since without this motivation any attempt is futile. Today numerous quitting strategies exist, either of pharmacological or non-pharmacological type, which are also advantageous for the elderly person. Approved pharmacological treatments include nicotine replacement therapies, bupropion, drugs targeting cannabinoid receptors and newer pharmacological approaches including the selective nicotinic partial agonists. Varenicline, an alpha4 beta2 nicotinic acetylcoline receptor partial agonist, is the most recently agent approved for smoking cessation. This drug works by reducing the strength of the smoker's urge to smoke and by relieving withdrawal symptoms. The most effective smoking cessation programs involve a combination of pharmacotherapy and behavioural and/or cognitive counselling to improve abstinence rates.

Aims: The complex pathogenesis of acute myocardial infarction (AMI) implicates phenotypic and genetic heterogeneity. In this pilot case-control study single nucleotide polymorphism (SNP) in several inflammatory genes, such as interleukin (IL)-1β, IL-6, IL- 10, α-1-antichymotrypsin (ACT), tumor necrosis factor alpha (TNF)-α and interferon gamma (IFN)-γ genes along with SNPs of genes regulating vascular functions (vascular endothelial growth factor; VEGF) and cholesterol synthesis (hydroxy-methyl-glutaryl CoA reductase; HMGCR) were investigated. Methods: Patients were genotyped with RT-PCR technique and data were analyzed with a new mathematical algorithm named Auto Contractive Map. Results: The Auto Contractive Map (AutoCM), was applied in AMI patients with the aim to detect and evaluate the relationships among genetic factors, clinical variables and classical risk factors. Genes were selected because their strong regulatory effect on inflammation and SNP in these gene were located in the promoter region. In the connectivity map generated by AutoCM a group of variables was directly linked with the AMI status; these were: gender (male), early age at onset (50-65 years), HMGCR gene (CC wild type genotype), IL-1βCT, IL-6 GG and VEGF CC genotypes. This direct link suggested a possible pathogenetic association with AMI. Other genetic, clinical and phenotypic variables were associated to the disease under a statistically defined hierarchy showed in the new connectivity map generated by AutoCM. Conclusion: These analyses suggested that genotypes of few inflammatory genes, a SNP in HMGCR gene, middle age, gender, low HDL and diabetes were very informative variables to predict the risk of AMI.

Introduction: Centenarians are reservoirs of genetic and environmental information to successful ageing and local centenarian groups may help us to understand some of these secrets. The current centenarian cohort in Belfast survived the 1970s epidemic of death from coronary heart disease in Northern Ireland, where cardiovascular mortality was almost highest in the world. These centenarians provided an opportunity to assess biological and genetic factors important in cardiovascular risk and ageing. Methods: Thirty-five (27 female, 8 male) centenarians, participants of the Belfast Elderly Longitudinal Free-living Ageing STudy (BELFAST), were community-living and of good cognition at enrolment. Results: Centenarians showed median Body Mass Index (BMI) at 25.7, systolic blood pressure 140mmHg and diastolic blood pressure 90mmHg respectively, and fasting glucose of 5.54mmol/l with no sex-related difference. Lipoproteins showed median cholesterol 5.3, High Density Lipoprotein (HDL) 1.10 and Low Density Lipoprotein (LDL) 3.47mmol/l respectively. Centenarian smokers showed no different blood pressure or lipid measurements compared with non-smokers. Malondialdehyde, a measure of lipid peroxidation, was low at 1.19 umol/l, and measures of antioxidant status showed variable results. Male centenarians did not carry any of the vascular risk genotypes studied ApoE4 for Apolipoprotein E (ApoE), DD for Angiotensin-Converting Enzyme (ACE), and TT for Methylene Tetrafolate-dehydrogenase reductase (MTHFR), though this is not true for female centenarians. Conclusions: This small local study shows, that Belfast centenarians carry a reasonably favourable risk profile with respect to cardiovascular disease. There is also some evidence suggesting that vascular risk factors and genotypes may be tolerated differently between the male and female centenarians. Maintaining an optimal cardiovascular risk profile seems likely to improve the chance of becoming a centenarian, especially for males.

A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0.039) genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers (HRR=0.550; p=0.015). On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers. This result corroborates our previous observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype.

Human aging and longevity are complex and multi-factorial traits that result from a combination of environmental, genetic, epigenetic and stochastic factors, each contributing to the overall phenotype. The multi-factorial process of aging acts at different levels of complexity, from molecule to cell, from organ to organ systems and finally to organism, giving rise to the dynamic “aging mosaic”. At present, an increasing amount of experimental data on genetics, genomics, proteomics and other -omics are available thanks to new highthroughput technologies but a comprehensive model for the study of human aging and longevity is still lacking. Systems biology represents a strategy to integrate and quantify the existing knowledge from different sources into predictive models, to be later tested and then implemented with new experimental data for validation and refinement in a recursive process. The ultimate goal is to compact the new acquired knowledge into a single picture, ideally able to characterize the phenotype at systemic/organism level. In this review we will briefly discuss the aging phenotype in a systems biology perspective, showing four specific examples at different levels of complexity, from a systemic process (inflammation) to a cascade-process pathways (coagulation) and from cellular organelle (proteasome) to single gene-network (PON-1), which could also represent targets for anti-aging strategies.

Objective: The aim of this study was to verify the effects of Italian Mediterranean Diet (IMD), consisting of organic versus conventional foods, on body composition, and biochemical parameters in a healthy individuals and in Chronic Kidney Disease (CKD) patients, in order to decrease cardiovascular diseases (CVD) risk factor and the progression of renal diseases. Design: After providing a written fully informed consent to the study, 150 Caucasian Italian men were recruited: 100 healthy male individuals (mean age 44,66±13,98 years; range 30-65 years) and 50 male CKD patients (mean age 46,25±5,97 years; range 42-54 years). These patients were affected by stage 2 and 3 of Chronic Renal Failure according to the K-DOQI 2003. Usual dietary intake and physical activity, during the previous 12 months were estimated by a semiquantitative food-frequency questionnaire. The following were measured at baseline and after consumption of conventional/organic 14 days IMD: Body mass index (BMI), Body composition, by Dual- X absorptiometry (DXA) scanner, total plasma homocysteine (tHcy), serum phosphorus, glycemia concentrations, lipid profile, and microalbuminuria. Results: A significant reduction of total homocysteine (tHcy) and phosphorus blood values were observed in the studied subjects. Body composition analysis by DXA highlighted high significant differences between conventional (T0) and organic diet (T1) for fat mass parameter, expressed as kilograms and as percentage (p<0.001). Improvement of lean body mass was observed in CDK patients (p=0.004). Conclusions: Our study clearly demonstrates that the Italian Mediterranean Organic Diet (IMOD), according to the “Nicotera diet”, was able to reduce tHcy, phosphorus, microalbuminuria levels and CVD risk in healthy individuals and in CDK patients.

Different lines of evidence suggest that higher intake of fiber may somehow protect against metabolic syndrome. The prebiotic inulin has widely been studied in relation to its putative beneficial effects on lipid and glucose metabolism. Therefore, adding inulin to diet may be a suitable strategy to prevent metabolic syndrome. Aim of the present study was to evaluate the effects of the daily consumption of inulin-enriched pasta on lipid and glucose metabolism as well as on gastrointestinal motility in young healthy subjects. Methods. Twenty-two healthy young male volunteers entered a randomized double blind cross-over study consisting of a 2-weeks run-in period, two 5-weeks study periods (11% inulin-enriched or control pasta), and an 8-weeks wash-out period in between. Serum lipid and glucose concentrations were evaluated by routine biochemical analyses. Gastric emptying time and electrical activity were non-invasively evaluated by ultrasound and electrogastrography. Data were analyzed by Friedman Repeated Measures ANOVA test. Results. Significant differences among baseline and the treatment group were found for HDL-cholesterol (p=0.004), total cholesterol/HDL-cholesterol ratio (p=0.006), triglycerides (p=0.04), fasting glucose level (p=0.044), fructosamine (p=0.0478), HbA1c (p=0.04), and homeostatic model assessment (HOMA-IR) (p=0.045). The gastric emptying, expressed as final emptying time, was found significantly delayed in the group that assumed inulin-enriched pasta (p=0.008). Conclusions. Inulin-enriched pasta improved lipidic and glicidic metabolism as well as the insulin resistance in healthy young subjects. In addition, it delayed the gastric emptying time which may represent the physiological counterpart of its metabolic effects.

Over the past decades, the clinical relevance and biological significance of magnesium (Mg) have been documented. Deficiency in Mg, aside from having a negative impact on the energy production pathway required by mitochondria to generate ATP, also reduces the threshold antioxidant capacity of the aging organism and its resistance to free-radical damage. Mg also acts as an antioxidant against free radical damage of the mitochondria. Chronic inflammation and oxidative stress have both been identified as pathogenic factors in aging and in several age-related diseases. Chronic Mg deficiency results in excessive production of oxygen-derived free radicals and low grade inflammation. Aging is very often associated with Mg inadequacy and with increased incidence of many chronic diseases, muscle loss and sarcopenia, altered immune responses, and vascular and metabolic conditions, such as atherosclerosis, diabetes and the cardiometabolic syndrome. The most common cause of Mg deficit in the elderly population is dietary Mg deficiency, although secondary Mg deficit in aging may also results from many different mechanisms. The aim of the present manuscript is to discuss the mechanisms and consequences of the modifications of Mg metabolism with age, the difficulties in the measurement of Mg status, and to review the current evidences suggesting that age-related chronic Mg deficits may be proposed as one of the physiopathological links that may help to explain the interactions between inflammation, and oxidative stress with the aging process and many age-related diseases.

Lipid peroxidation is believed to be the major biochemical alteration underling oxidant-induced cell injury in stress including numerous diseases. One of the natural molecules known to prevent or retardate oxidation is α-lipoic acid (α-LA) thus, the lipoic acid/dihydrolipoic acid (LA/DHLA) redox couple has received considerable attention. Recent studies highlighted the potential of free LA and DHLA as powerful metabolic antioxidants that are able to scavenge the reactive oxygen species and to recycle other antioxidants. Our aim was to investigate the effects of α-LA in the treatment of Italian pre-obese and obese patients. 1612 people were enrolled and 1127 of them (445 men and 682 women, 18-60 age) met criteria and were screened in the study. According to body mass index (BMI), 53% of them were obese, and 43% were pre-obese. They were treated for 4 months with 800 mg/day of α-LA. In the pre-obese group, significant reductions (p<0.001) of weight (8%, in both gender), BMI (2 points), blood pressure, and abdominal circumference (female 6 cm, male 7 cm) were observed. In the obese group, significant reductions (p<0.001) of weight (9%, in both gender), BMI (female 3 point, male 4 point), blood pressure and abdominal circumference (female 9 cm, male 11 cm) were highlighted. Our study indicated that α-LA is an ideal antioxidant candidate for the therapy of obesity related diseases. Further clinical studies should be considered to demonstrate the role and efficacy of α-LA treatment.

Chemoprevention by dietary constituents has recently emerged as a novel approach to control gastric cancer incidence. Over the past years, functional foods and food supplements, especially probiotics, have received much attention as potential dietary cancer prevention agents. The precise mechanisms by which these lactic cultures exert their antitumorigenic activities are not fully elucidated, but there is some evidence of their influence on cell proliferation and growth. Ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT) are the key enzymes involved in polyamine biosynthesis and catabolism, respectively. These polycationic compounds are significantly associated with cancer risk and represent a specific markers for neoplastic proliferation. The aim of this study was to investigate the effects of increasing concentrations of Lactobacillus rhamnosus strain GG (ATCC 53103) (L. GG) homogenate on polyamine biosynthesis and polyamine degradation as well as on resulting polyamine levels in HGC-27 human gastric cancer cells. The influence of this probiotic on cell proliferation was also evaluated. Administration of probiotic homogenate significantly reduced both ODC mRNA and activity as well as polyamine content and neoplastic proliferation. Besides, an increase in both SSAT mRNA and activity occurred after LGG administration in HGC-27. These data suggest that a nutritional component such as the probiotic L. GG could be proposed in an alternative approach to prevention of gastric cancer. This strategy could overcome the limitations due to a prolonged use of drugs and/or the occurrence of their adverse effects, and it could reasonably also start at a young age.

Ten free-living elderly were administered with a synbiotic [fermented milk containing Lactobacillus rhamnosus Gorbach and Goldin (LGG®)] and oligofructose as a prebiotic for one month. Serum cytokines were evaluated before (T0) and after (T1) synbiotic administration. At T0, values of Interleukin (IL)-12, IL-6, IL-10, IL-1β and Tumor Necrosis Factor (TNF)-α were lower than normal controls, with the exception of IL-8, thus confirming previous results on the impairment of both innate and adaptive responses in elderly. At T1, the synbiotic was able to significantly increase, depressed values of IL-1β, IL-6 and IL-8 with a trend to a modest increase for the restant cytokines. In conclusion, the synbiotic used in this study seems to be very beneficial to elderly for its capacity to maintain the immune homeostasis, even if an increase in dosage and prolongation of administration time are required for a better modulation of the aged adaptive immune response.

The environmental impact as well as malnutrition are responsible for an increased incidence of inflammatory diseases with a consequential loss of immune homeostasis. Therefore, administration of nutraceuticals is aimed at reconstituting the immune balance in terms of the so-called immune nutrition. Among many known nutraceuticals, more recently, donkey's and goat's milks have been used as good alternatives to human and bovine milk in various clinical conditions such as allergy, atopy and inflammatory diseases. In fact, both milks possess immunomodulating capacities and release nitric oxide, a potent vasodilator endowed with anti-atherogenic properties. In this review, emphasis will be placed on the consumption of fermented milk and, in particular, on its ability to modulate the aged immune system, even including the intestinal mucosal immune response in elderly. Therefore, for their specific properties donkey's and goat's milk administration to aged people should be encouraged.

In a group of 14 healthy aged subjects, donkey and goat milk was administered respectively, for a period of one month. Cytokine profile [interleukin (IL)-12, IL-10, IL-1β, IL-8, IL-6 and Tumor Necrosis Factor (TNF)-α] was assessed before and after milk intake by means of a cytometric bead array test. Data demonstrated that IL-12 was undetectable, while IL-10, IL-1β and TNF-β were released in very low amounts. Quite interestingly, IL-8 was increased by donkey milk administration, while same cytokine was dramatically decreased following goat milk intake. Same pattern of response was noted with IL-6 even if levels of these cytokine were lower than those detectable in the case of IL-8. Taken together, these findings indicate that administration of donkey milk in the aged host is able to upregulate the immune response, while goat milk seems to reduce the exaggerated acute phase response in elderly.

The in vitro effects of goat's milk from different sources (Jonica, Saanen, and Priska breeds plus a commercial preparation) on healthy human peripheral blood mononuclear cells (PBMCs) were evaluated in terms of nitric oxide (NO) and cytokine release. According to the incubation time (24 h or 48 h) used all milks could induce release of NO from monocytes. In this context, however, in the presence of a commercial milk preparation inhibition of lypopolysaccharide (LPS)-induce NO generation was evident. Also polymorphonuclear cells stimulated with the various milks released detectable amounts of NO. In the case of Priska milk inhibition of LPS-mediated NO generation was observed. Despite a broad array of cytokines tested [Interleukin (IL)-4, IL-5, IL-6, IL-10, IL-12, IL-13, IL-17, Tumor Necrosis Factor (TNF)-α, Transforming Growth Factor-β and Granulocyte Colony Stimulating Factor] only IL-10, TNF-α, and IL-6 were released by PBMCs upon stimulation with various milks. Taken together, these data indicate that goat's milk for its capacity to produce NO may exert a cardioprotective and anti-atherogenic effect in consumers. Moreover, induction of proinflammatory (TNF-α and IL-6) and anti-inflammatory (IL-10) cytokines suggests the ability of this milk to maintain immune homeostasis in the immunocompromised host (e.g., aged people).

Regular consumption of cruciferous vegetables or spices is associated with a reduced incidence of cancer and reduction of markers for neurodegenerative damage. Furthermore, greater health benefit may be obtained from raw as opposed to cooked vegetables. Nutritional interventions, by increasing dietary intake of fruits and vegetables, can retard and even reverse age-related declines in brain function and cognitive performance. The mechanisms through which such dietary supplementation may diminish free radical-related diseases is related to their ability to reduce the formation of reactive oxygen and nitrogen species, along with the up-regulation of vitagenes, such as members of the heat shock protein (Hsp) family, heme oxygenase-1 and Hsp70. The most prominent dietary factor that increases the risk of many different chronic diseases is excessive calorie intake. Reducing energy consumption by controlled caloric restriction or intermittent fasting increases lifespan and protects various tissues against diseases, in part, by hormetic mechanisms that increase cellular stress resistance. This biphasic dose-response relationship (i.e., hormesis) displays low-dose stimulation and a high-dose inhibition. Despite the current interest in hormesis by the toxicology community, quantitatively similar U-shaped dose responses have long been recognized by researchers to be involved with factors affecting memory, learning, and the occurrence of oxidative stressmediated degenerative responses. Dietary polyphenols also act hormetically, displaying cytoprotective effects at low doses. However, excessive nutritional supplementation (i.e., high doses) can have negative consequences through the generation of more reactive and harmful intermediates with pathological consequences.

No genes exist that have been selected to promote ageing. The evolutionary theory of ageing tells us that there is a trade-off between body maintenance and investment in reproduction. It is commonly acceptable that the ageing process is driven by the lifelong accumulation of molecular damages mainly due to reactive oxygen species (ROS) produced by mitochondria as well as random errors in DNA replication. Although ageing itself is not a disease, numerous diseases are age-related, such as cancer, Alzheimer's disease, atherosclerosis, metabolic disorders and others, likely caused by low grade inflammation driven by oxygen stress and manifested by increased level of pro-inflammatory cytokines such as IL-1, IL-6 and TNF-α, encoded by genes activated by the transcription factor NF- κB. It is believed that ageing is plastic and can be slowed down by caloric restriction as well as by some nutraceuticals. As the low grade inflammatory process is believed substantially to contribute to ageing, slowing ageing and postponing the onset of age-related diseases may be achieved by blocking the NF-κB-dependent inflammation. In this review we consider the possibility of the natural spice curcumin, a powerful antioxidant, anti-inflammatory agent and efficient inhibitor of NF-κB and the mTOR signaling pathway which overlaps that of NF-κB, to slow down ageing.

Body mass index (BMI), serum cytokines and serum obesity markers were evaluated in 33 obese children before, during and after a hypocaloric diet. The cytometric bead array “human inflammatory kit” was used for the evaluation of serum interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor-... On the other hand, the following obesity biomarkers were evaluated by means of a flowcytomixhuman obesity 9 plex kit: Soluble Isoform of CD40 Ligand; Soluble Intercellular Adhesion Molecule-1; Leptin; Monocyte Chemoattractant Protein 1; Myeloperoxidase; Osteoprotegerin; Resistin and Soluble TNF-receptors. Actually, throughout the study modifications of BMI were negligible and, therefore, serum cytokines and obesity markers did not show any significant changes in comparison with baseline values. On the other hand, at the different time points considered the majority of obesity markers were higher than normal controls, thus indicating a low grade inflammation in childhood obesity. Therefore, attempts at reducing this inflammatory status in children which predisposes to the metabolic syndrome outcome are discussed.