Lipid-lowering effect of bergamot polyphenolic fraction: role of pancreatic cholesterol ester hydrolase.

Bergamot polyphenolic fraction (BPF) has been shown to positively modulate several mechanisms involved in metabolic syndrome, suggesting its use in therapy. In particular, it is able to induce a significant amelioration of serum lipid profile in hyperlipemic patients at different levels. The purpose of our study was to investigate the effect of BPF on cholesterol absorption physiologically mediated by pancreatic cholesterol ester hydrolase (pCEH). An in vitro activity assay was performed to study the effect of BPF on pCEH, whereas the rate of cholesterol absorption was evaluated through in vivo studies. In particular, male, Sprague-Dawley rats (200–225 g) were fed either normal chow or chow supplemented with 0.5% cholic acid, 5.5% peanut oil, and varying amounts of cholesterol (0 to 1.5%). BPF (10 mg/Kg) was daily administrated by means of a gastric gavage to animals fed with lipid supplemented diet for 4 weeks and, at the end of the study, plasma lipids and liver cholesteryl esters were measured in all experimental groups. Our results show that BPF was able to inhibit pCEH activity and this effect was confirmed, in vivo, via detection of lymphatic cholesteryl ester in rats fed with a cholesterol-rich diet. This evidence clarifies a further mechanism responsible for the hypolipemic properties of BPF previously observed in humans, confirming its beneficial effect in the therapy of hypercholesterolemia and in the treatment of metabolic syndrome.

Olea Europea-derived phenolic products attenuate antinociceptive morphine tolerance: an innovative strategic approach to treat cancer pain.

Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.

Effect of MN (III) tetrakis (4-benzoic acid) porphyrin by photodynamically generated free radicals on SODs keratinocytes.

Superoxide, a reactive form of oxygen, can be produced in vivo either in normal and under pathophysiologic conditions or by photosensitizing chemicals, as during photodynamic treatment. Photodynamic therapies (PDT), widely adopted in Dermatology and Oncology, are known to generate reactive oxygen species (ROS) and may contribute to structural alterations and oxidatively generated modifications of cellular antioxidants. We hypothesized that over-production of free radicals would decrease the enzymatic activities of endogenous cellular antioxidants. To test this hypothesis, keratinocytes were treated with the photosensitizer Photofrin plus visible light to produce free radicals and CuZnSOD and MnSOD activities were measured. Photodynamic treatment of keratinocytes increases malonylaldehyde production, nitrotyrosine staining and superoxide production. The enzymatic activities of CuZnSOD and MnSOD were significantly decreased after Photofrin plus visible light treatment. Our results suggest that the main cellular antioxidant system can be inactivated by photodynamically generated ROS. Pretreatment of keratinocytes with free radicals scavenger such as Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) was able to restore the endogenous antioxidant system activities, inhibiting the MDA formation, nitrotyrosine staining and superoxide formation. Antioxidant therapy could therefore be a useful tool in protecting healthy epidermal cells against common side effects induced by antitumor targeted therapies.

Montelparo study: risk factors for age-related macular degeneration in a little rural community in Italy.

PURPOSE: To evaluate the prevalence of age-related maculopathy (ARM) and age-related macular degeneration (AMD) lesions. Secondary outcome includes to examine 16 potential risk factors and their prevalence for attribution of risk for ARM and AMD in Montelparo, a small, rural and homogeneous population in central Italy. MATERIALS AND METHODS: A population aged 65 years old and over underwent a detailed interview about demographic notices and possible main risk factors for ARM and AMD. The following information were assessed as medical variables with bivariate analysis: demographic variables such as age and gender, dietary intake (meat, alcohol, fresh and cooked vegetables, fruit and fish), lifestyle factors (smoking, time of sunlight exposure, physical activity), medical history (cataract, hypertension, glaucoma, drug intake and body-mass index). Clinical examination included visual acuity measurement, anterior and posterior segment examination, fundus photography grading using The International Classification and Grading System. Any image was further classified according to the Clinical Age-Related Maculopathy Staging (CARMS) system. RESULTS: 210 patients (79%) of a farmer community participated the study. Prevalence of ARM resulted in 38.5%, drusen larger than 125 micron were found in 14.81%, AMD was 4.28%. The attributable risk estimate, reveal that age (p = 0.014), prior cataract surgery (p = 0.00) and hypertension history (p = 0.005), have the greatest impact on the prevalence of ARM in the community. A vegetable based diet, seems to prevent such effect (p = 0,007). CONCLUSIONS: This study show age as the only dominant invariable factor. Prior cataract surgery and hypertension seems to play an effective role in increasing the risk of maculopathy. Our results provides further evidence that a diet poor in alcohol, rich in vegetables and in polyunsaturated fat could reduce risk of AMD.

Age-related macular disease in rural southern Italy.

OBJECTIVE: To report the prevalence of age-related maculopathy (ARM) in Salandra, a small, isolated southern Italian community, to test the hypothesis that an environmental factor, scarce in such a remote community but ubiquitous in modern industrial societies, might modify the risk of developing ARM. DESIGN: Population-based cross-sectional survey. MAIN OUTCOME MEASURES: Prevalence of advanced age-related macular degeneration (ARMD) (geographic atrophy or exudative maculopathy) and ARM (large, soft drusen or retinal pigment epithelium changes, or both) defined by fundus biomicroscopy and 30 degrees stereoscopic, macular photography. Self-sustenance was assessed by interview of participants and local shop retailers. The degree of genetic isolation was computed using a model that fits the genetic population structure with the frequency distribution of surnames in the community. RESULTS: A full ophthalmic examination was undertaken in 366 (63.5%) of 576 eligible participants, 354 (96.7%) of whom had clinical or photographic assessment for the presence of ARMD and 310 (84.6%) of whom had drusen characteristics graded on color transparencies for ARM. The overall prevalence of ARMD was 1.1%. Drusen larger than 50 microns and more numerous than 10 were found in 4.5% of subjects. Salandra was the birthplace of 87.2% of participants and for 77.3% of both parents of each subject. People in the community tended to consume homegrown products. CONCLUSION: The prevalence of ARM may be lower in this self-sustained farming community than elsewhere in the industrialized world.