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.
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.
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 (T(0)) and organic diet (T(1)) 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).
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.
Impairment of the immune response and aberrant expression of microRNAs are emerging hallmarks of tumour initiation/progression, in addition to driver gene mutations and epigenetic modifications. We ...performed a preliminary survey of independent adenoma and colorectal cancer (CRC) miRnoma data sets and, among the most dysregulated miRNAs, we selected miR-27a and disclosed that it is already upregulated in adenoma and further increases during the evolution to adenocarcinoma. To identify novel genes and pathways regulated by this miRNA, we employed a differential 2DE-DIGE proteome analysis. We showed that miR-27a modulates a group of proteins involved in MHC class I cell surface exposure and, mechanistically, demonstrated that calreticulin is a miR-27a direct target responsible for most downstream effects in epistasis experiments. In vitro miR-27a affected cell proliferation and angiogenesis; mouse xenografts of human CRC cell lines expressing different miR-27a levels confirmed the protein variations and recapitulated the cell growth and apoptosis effects. In vivo miR-27a inversely correlated with MHC class I molecules and calreticulin expression, CD8(+) T cells infiltration and cytotoxic activity (LAMP-1 exposure and perforin release). Tumours with high miR-27a, low calreticulin and CD8(+) T cells' infiltration were associated with distant metastasis and poor prognosis. Our data demonstrate that miR-27a acts as an oncomiRNA, represses MHC class I expression through calreticulin downregulation and affects tumour progression. These results may pave the way for better diagnosis, patient stratification and novel therapeutic approaches.
Lipid peroxidation has supposed as the major biochemical alteration underling oxidant-induced cell injury in stress including numerous diseases. One of the natural molecules know to prevent or retard ...oxidation is alpha-lipoic acid (LA) and, therefore, the lipoic acid/dihydrolipoic acid (LA/DHLA) redox couple has received considerable attention. Recent studies have highlighted the potential of free LA and DHLA as powerful metabolic antioxidants that are able to scavenge the reactive oxygen species, to recycle other antioxidants. Our aim was to investigate the beneficial effects of LA in the treatment of Italian pre-obese and obese subjects. We screened 1612 subjects for enrollment; of these, 1127 subjects (445 men and 682 women, 18-60 age) met enrolment criteria and were enrolled in the study. According to body mass index (BMI) the 53% was obese and the 43% was pre-obese. The subjects were treated for 4 month with 800 mg/day of LA. In pre-obese subject significant reduction (p<0.001) of weight (8%, both gender), BMI (2 points), blood pressure, and abdominal circumference (female 6 cm, male 7 cm) were observed. In obese subjects significant reductions (p<0.001) of weight (9%, both gender), BMI (female 3 point, male 4 point), blood pressure and abdominal circumference (female 9 cm, male 11 cm) were observed. Our study indicated that LA is an ideal antioxidant candidate for the therapy of obesity related diseases. Further clinical studies should be considered to highlight the role and efficacy of LA treatment.
Insulin resistance and obesity are intimately related to a chronic low grade systemic inflammation. Interleukin-6 (IL-6) may influence the pathogenesis of obesity-related diseases. The aim of this ...study is to investigate the effect of body's fat mass on the relationships between -174G/C IL-6 promoter gene polymorphism, IL-6 circulating level and insulin resistance. A population of 150 Caucasian women was studied, subdivided according to their body composition in non-obese (NW), Normal Weight Obese (NWO) and preobese-obese (OB). The NWO subjects were found in an intermediate position between the NW and OB subjects in terms of body weight, fat mass percentage (FM%), abdominal FAT%, hs-CRP and plasma triglyceride level. Fasting plasma IL-6 concentration was positively correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) in all subjects analyzed (P=0.0014). In NWO and OB women a significantly increased IL-6 mean value was observed compared with NW subjects. In G/G population, the IL-6 plasma level of NWO and OB was significantly higher with respect to NW. No significant differences of IL-6 concentrations were observed in the three groups carrying G/C genotype. NWO and OB women homozygous for the allele C have significantly lower value of IL-6 with respect to NW subjects. IL-6 concentration was positively correlated with FM% in G/G (R(2)=0.397, P<0.001) and was negatively correlated in C/C (R(2)=0.459, P=0.002). No significant correlation was observed in G/C genotype (R(2)=0.041, P=0.173). In conclusion our study confirms that, at least in Italian Caucasian females, the FM% is a major determinant of an increase in IL-6 production and insulin resistance. -174 G/C IL-6 promoter polymorphism represents a marker which could help to identify, time in advance, "vulnerable" individuals at risk of age and obesity related diseases.
Purpose
Sabarubicin (MEN 10755), a new disaccaride anthracycline, has shown greater efficacy than Doxorubicin in a large panel of preclinical models and now it is in phase II clinical trials. Its ...promising antitumour activity promoted considerable interest to combine Sabarubicin with other antitumour agents. Thus, the purpose of this study was to evaluate in vitro cytotoxic effects and in vivo antitumour activities produced by the combination of Sabarubicin and cisplatin (DDP).
Methods
The antitumour effect of Sabarubicin and DDP association was investigated, in vitro and in vivo, in preclinical models of lung cancer i.e.: the non-small cell lung carcinoma (NSCLC) H460 and the small-cell lung carcinoma (SCLC) GLC4 in terms of synergism, additivity or antagonism in order to establish the best schedule for the combined treatment. Further, the correlation between antitumour activity and the pharmacokinetic parameters of the studied combination was also evaluated.
Results
The drug combination in vitro was in general more cytotoxic than the single drug alone, indicating the presence of a synergistic effect in both tumour cell lines. Also, in the xenograft experiments a superior antitumoral effect was observed when Sabarubicin was combined with DDP. The antitumour efficacy of Sabarubicin (6 mg/kg q4d × 5) combined with DDP (6 mg/kg q4d × 3) greatly depended on the schedule of administration. In H460 tumour line, the sequential combination was more effective than the simultaneous administration of the two agents, although the antitumour efficacy was not dependent on the sequence of combination. On the other hand, a strong sequence-dependent effect was observed when Sabarubicin was combined with DDP in SCLC, GLC4. In particular, the highest value of LCK = 6.7 was obtained when administration of DDP followed by 24 h that of Sabarubicin. Pharmacokinetics of Sabarubicin in combination with DDP was evaluated at 6 mg/kg for both drugs with different sequential schedule. The experimental data showed no evidence for pharmacokinetics drug–drug interaction.
Conclusion
These preclinical results indicate the potential for a strong antitumour activity in lung tumours of the combination Sabarubicin and DDP. In particular, in SCLC the best response should be given by a sequence with administration of Sabarubicin followed 24 h later by that of DDP. Clinical trials based on these results are ongoing.
The purpose of this study was to identify new indexes of body composition that characterize the normal weight obese (NWO) women. We measured body composition by dual energy x-ray absorptiometry (DXA) ...and resting metabolic rate (RMR) by indirect calorimetry in a cohort of seventy-five healthy Italian women, subdivided into three groups (nonobese/controls, NWO, preobese-obese women). Despite a normal body mass index (BMI), the NWO women have a higher body fat mass percentage (FAT %) (38.99 +/- 6.03) associated to a significant (p = 0.02) lower amount of lean mass of legs (12.24 +/- 1.31) and lean mass of left leg (6.07 +/- 0.64) with respect to the control group. The NWO group showed a significant (p = 0.043) lower RMR (1201.25 +/- 349.02) in comparison with nonobese and preobese-obese women. To classify NWO individuals among general population, we identified three significant body composition indexes: abdominal index, leg index and trunk index. The NWO women showed significant increased value in the three indexes (p < 0.001). Our results suggest that, despite a normal BMI, the NWO women displayed a cluster of anthropometric characteristics (body fat mass percentage, leg indexes) not different to obese women ones. An appropriate diet-therapy and physical activity may be protecting NWO individuals from diabetes and cardiovascular diseases associated to preobese-obese women.
A constantly growing part of consumers considers the organic foods healthier than the conventional foods. However, so far few nutritional intervention studies in humans are available on the ...comparison of organic and conventional food products.
The aim of the present work was to compare the total antioxidant activity of organic versus conventional fruits (apples, pears, red oranges, lemons, strawberries and bananas), vegetables (lettuces, tomatoes, onions, garlics, carrots, beans, potatoes, celeries, peas, courgettes and zucchinies), red wine and milk.
The oxygen radical absorbing capacity (ORAC) procedure was used to determine both the antioxidant activity of food from organic or conventional origin, and the human plasma antioxidant capacity. Ten Caucasian Italian men, aged 30-65 years, were recruited. The subjects were healthy, according to the clinical examination and the disease history, none smoked or took any drug. Anthropometric parameters of all the participants were measured.
The ORAC values of most part of organic foods, i.e. fruits, vegetables as well as red wine and milk were significantly (p < 0.005) higher than those of the conventional homologues. Three organic foods, i.e. pears (-25%) (p < 0.01), lettuces (-20%) (p < 0.01), and tomatoes salsas (-4%) showed ORAC values lower than the conventional homologues. After the consumption of 14 days Mediterranean organic diet a significant (p < 0.005) increase (21%) of the human plasma total antioxidant capacity was observed.
Our results clearly show that the organic food products have an higher total antioxidant activity and bioactivity than the conventional foods. The results could be used in public health campaign to increase the consumption of products able to provide a significant health protection and prevention of chronic diseases.
Astrocytes harbour functional receptors to many neurotransmitters, including substance P (SP), an undecapeptide belonging to the tachykinin family of peptide transmitters. SP activates malignant ...glial cells to induce cytokine release and proliferation, both responses being relevant for tumour progression. In tumours developed in nude mice transplanted subcutaneously (s.c.) to U373 MG human glioma cells, the presence of SP was observed at immunohistochemistry. Although the administration of exogenous SP did not significantly affect the size or development of U373 MG xenograft, a role of SP in supporting glioma progression in vivo was highlighted by the tumour growth inhibition induced by highly specific and selective human tachykinin NK1 receptor antagonists (MEN 11467 and MEN 11149). The anti-tumour activity of MEN 11467 was observed both with s.c. or intravenous treatments and was partially reverted by the concomitant administration of exogenous SP. Doxorubicin did not show any activity in controlling U373 MG growth in this in vivo model. A novel therapeutic approach to treat malignant gliomas with tachykinin NK1 receptor antagonists is suggested by these findings.
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