Phenolics from olive oil and its waste products. Biological activities in in vitro and in vivo studies.
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Animals↗
Biomedical subjects
C Galli
Publications and source records attributed to C Galli.
Statins enhance arachidonic acid synthesis in hypercholesterolemic patients.
BACKGROUND AND AIM: It has been shown that statins enhance arachidonic acid biosynthesis from linoleic acid in vitro, and there is also evidence that statin-treated patients have high plasma and cellular arachidonic acid levels. The aim of this study was to investigate the possible effects of statins on the desaturating steps of arachidonic acid biosynthesis in patients. METHODS AND RESULTS: Plasma polyunsaturated fatty acids (percentages and concentrations), total cholesterol, LDL-cholesterol and triglycerides were measured in three groups of hypercholesterolemic patients before and after treatment with statins or fibrates for about three years, or before and after four months on a low-fat diet. As expected, there was a significant reduction in plasma total cholesterol (-23%) and LDL-cholesterol (-27%) levels in the statin group, and a significant reduction in triglycerides (-29%) and some decrease in total cholesterol (-12%) in the fibrate group; no change was observed in the control group. The selective increase in plasma arachidonic acid levels (in terms of absolute concentration and as a percentage of total fatty acids) was of the same order as the reduction in cholesterol, and the selective increase in the product/precursor ratios for delta 5 desaturation in the statin group indicated that this key step in arachidonic acid synthesis is affected. CONCLUSIONS: Our data show that an increase in arachidonic acid synthesis due to enhanced delta 5 desaturation is a major effect of statin treatment, and has the same order of magnitude as the reduction in plasma cholesterol levels.
Anticholesteremic Agents↗
Olive oils rich in natural catecholic phenols decrease isoprostane excretion in humans.
This study was undertaken to evaluate, in humans, the antioxidant activity of olive oil phenolics, namely hydroxytyrosol and oleuropein aglycone that share an orthodiphenolic (catecholic) structure. Human volunteers were administered olive oil samples containing increasing amounts of an olive oil phenolic extract that was characterized by gas-chromatography/mass spectrometry. The administration of phenol-rich oils was dose-dependently associated with a decreased urinary excretion of 8-iso-PGF(2alpha), a biomarker of oxidative stress. Also, a statistically significant negative correlation between homovanillyl alcohol (HValc, hydroxytyrosol's major metabolite, formed through the COMT system) and F(2)-isoprostanes excretion was found. Thus, the administration of oil samples with increasing, albeit low, concentrations of orthodiphenolic compounds, namely hydroxytyrosol and oleuropein aglycone, results in a dose-dependent reduction in the urinary excretion of 8-iso-PGF(2alpha). The statistically significant negative correlation between 8-iso-PGF(2alpha) and HValc urinary concentrations suggests that this metabolite better reflects the in vivo activities of hydroxytyrosol.
Adult↗
Olive phenol hydroxytyrosol prevents passive smoking-induced oxidative stress.
BACKGROUND: Oxidative stress is involved in the onset of several degenerative disorders, and epidemiological studies indicate that a high intake of dietary antioxidants, as in the case of the Mediterranean basin, is protective. Olive mill waste waters (OMWWs) are a byproduct of olive oil production rich in phenolic antioxidants, such as hydroxytyrosol. We tested the effects of a low dose of an OMWW extract in a model of sidestream smoke-induced oxidative stress in rats by evaluating the urinary excretion of 8-iso-prostaglandin (PG) F(2alpha) (iPF(2alpha)-III). METHODS AND RESULTS: An OMWW extract (5 mg/kg, providing 414 microg/kg of hydroxytyrosol) was administered to rats daily for 4 days, during which time the animals were exposed to sidestream smoke for 20 minutes once a day. Daily urines were collected, and the urinary excretion of 8-iso-PGF(2alpha) was evaluated as an index of oxidative stress-induced in vivo lipid peroxidation. The exposure of rats to passive smoking increased the urinary excretion of 8-iso-PGF(2alpha) by 44+/-4.2% at 48 hours and by 55+/-10% at 96 hours. Treatment with the OMWW extract was able to completely prevent the increase at 48 hours and resulted in lower increments (34+/-18% versus 55+/-10%) of 8-iso-PGF(2alpha) excretion at 96 hours. CONCLUSIONS: A low dose of hydroxytyrosol, administered through OMWW, reduces the consequences of sidestream smoke-induced oxidative stress in rats.
Animals↗
Diet and prevention of coronary heart disease: the potential role of phytochemicals.
Epidemiological studies, and some clinical trials, demonstrate that a proper diet reduces the rate of occurrence of cardiovascular disorders. Several in vitro studies suggest that some components of plant foods, most of which sharing a phenolic structure, are endowed with interesting 'pharmacological activities'. This article reviews the evidence that links a high dietary intake of phytochemicals from various sources with a reduced incidence of coronary heart disease.
Cacao↗
Testosterone metabolites in patients reduce the levels of very long chain fatty acids accumulated in X-adrenoleukodystrophic fibroblasts.
Testosterone metabolites (dihydrotestosterone, DHT) and 5 alpha-androstan-3 alpha,17 beta-diol (3 alpha-diol), but not testosterone itself, were shown to reduce the levels of very long chain fatty acids which accumulate in cultured skin fibroblasts from X-adrenoleukodystrophic patients (X-ALD). In addition, in X-ALD fibroblasts, testosterone is less actively converted into DHT vs. controls (skin fibroblasts retrieved from normal subjects) whereas the additional conversion of DHT to the final product 3 alpha-diol is enhanced. This is the first report of altered testosterone metabolism in X-ALD fibroblasts and of the effects of androgens in lowering the abnormal accumulation of very long chain fatty acids in this type of cells.
Adrenoleukodystrophy↗
The insulin-dependent glucose transporter isoform 4 is expressed in bovine blastocysts.
We have investigated the expression of two glucose transporter isoforms, Glut1 and 4, in 14- and 16-day-old bovine blastocysts (d14, d16) using RT-PCR, competitive RT-PCR and in situ hybridization. The blastocysts were grown in vivo or had been produced in vitro. Glut1 mRNA was detected in all blastocysts studied, Glut4 in all d14 blastocysts, but only in a few d16 blastocysts. Glut4 mRNA was localized in trophoblast and endoderm cells. Glut1 mRNA increased from d14 to d16 while Glut4 transcription was down-regulated in d16 blastocysts. The mRNA amounts varied between 0.8 to 23 pg and 3.9 to 65 fg per 100 ng embryonic RNA for Glut1 and Glut4, respectively, displaying a 100- to 1500-fold lower expression of Glut4 compared with Glut1 during blastocyst elongation. This is the first report on the expression of the insulin-sensitive Glut4 isoform in mammalian preimplantation embryos.
Animals↗
Endogenous APP derivatives oppositely modulate apoptosis through an autocrine loop.
We have recently shown that, in rat cerebellar granule cells, apoptosis triggered by KCl deprivation is associated with an amyloidogenic shift in the processing of amyloid precursor protein (APP) resulting in an increase of amyloid beta-protein (A beta) secretion. To further investigate this issue we studied the relationship between secretion of APP metabolites (A beta, APPs) and neuronal degeneration. We postulated that the endogenous products of the APP metabolism may modulate neuronal survival by an autocrine loop. Treatment of cerebellar granule cells with various antibodies raised against different epitopes of APPs and A beta oppositely modulates low potassium apoptotic cell death. Antibodies specific for the N-terminal of A beta (4G8, 6E10, R3659) increased neuronal survival by 30% over controls. On the contrary, treatment of cultures undergoing apoptosis with the monoclonal antibody 22C11 directed against the APP N-terminus reduced neuronal survival by 53%, suggesting that endogenous alpha-APPs contribute to neuronal survival. Moreover low KCl culture medium, conditioned by cerebellar granule cells, attenuated the apoptotic process. This anti-apoptotic effect was abolished by removal of APPs from the conditioned medium. Western blotting of APPs removed from the conditioned medium confirmed the presence of alpha-APPs. These data indicate that APP cleavage products oppositely modulate neuronal survival through an autocrine loop and further strengthen an Alzheimer's disease pathogenetic scheme based on altered metabolism of APP.
Amyloid beta-Protein Precursor↗
In vitro differentiation of human monocytes to macrophages results in depletion of antioxidants and increase in n-3 fatty acids levels.
The lipid composition and alpha-tocopherol content of human monocytes were investigated before and after their differentiation to macrophages. The total lipid and protein content per number of cells increased after the differentiation of monocytes by approximately four-fold; a two-fold increase in docosahexaenoic and docosapentaenoic acids and a two-fold decrease in linoleic acid were also noted. As opposed to an initial monocytic vitamin E content of 4.75 pmol/10(6) cells, macrophagic vitamin E levels were undetectable. Changes in vitamin E and fatty acids contents in macrophages, with respect to monocytes, appear to reflect the lipid composition of fetal calf serum, that is low in vitamin E and has a proportionally higher docosahexaenoic acid content than adult human serum.
Adult↗
Olive oil phenolics are dose-dependently absorbed in humans.
Olive oil phenolic constituents have been shown, in vitro, to be endowed with potent biological activities including, but not limited to, an antioxidant action. To date, there is no information on the absorption and disposition of such compounds in humans. We report that olive oil phenolics, namely tyrosol and hydroxytyrosol, are dose-dependently absorbed in humans after ingestion and that they are excreted in the urine as glucuronide conjugates. Furthermore, an increase in the dose of phenolics administered increased the proportion of conjugation with glucuronide.
Adult↗
Very low intakes of N-3 fatty acids incorporated into bovine milk reduce plasma triacylglycerol and increase HDL-cholesterol concentrations in healthy subjects.
Eight normolipidaemic volunteers, habitual partial skim milk drinkers and non-eaters of fish during the study, were given 500 ml day(-1) of partial skim milk for 1 month; they were then switched to 500 ml day(-1) of a novel commercially available milk preparation, supplying 400 mg of N-3 fatty acids-of which 300 mg were EPA+DHA-and 15 mg vitamin E, for 6 weeks. No changes in plasma lipid parameters were observed after the first run-in month; at 3 and 6 weeks on the N-3-rich milk, marked increments of plasma EPA (44 and 31%, respectively) and DHA (13 and 31%, respectively) were observed. Triacylglycerol (TG) concentrations decreased by 19% and high-density lipoprotein (HDL) concentrations increased by 19% at 6 weeks; plasma vitamin E rose by 21% while the susceptibility of plasma to oxidation was unaffected. Correlations were found between plasma EPA or DHA and TG, cholesterol, and HDL. In conclusion, the intake of a milk preparation providing low amounts of EPA+DHA to healthy individuals led to marked increases of N-3 fatty acids and vitamin E in plasma and in associated favourable changes in HDL and TG.
Adult↗
Granule neuron DNA damage following deafferentation in adult rats cerebellar cortex: a lesion model.
Neuronal programmed cell death is regulated by a neurotrophic supply from targets and afferent inputs. The relative contribution of each component varies according to neuronal type and age. We have previously reported that primary cultures of cerebellar granule cells undergo apoptosis when deprived of depolarising KCl concentrations, suggesting a significant role of afferent inputs in the control of cerebellar granule cells survival. This issue was investigated by setting up various in vivo lesional paradigms in order to obtain partial or total deafferentation of the cerebellar granule layer in adult rats. At different times after surgery, cerebellar sections were subjected to TUNEL staining in order to detect possible DNA damage. One week after unilateral pedunculotomy, few scattered groups of apoptotic granule neurons were observed in the homolateral hemisphere. On the contrary, total deafferentation obtained by a new experimental paradigm based on an "L-cut" lesion induced massive and widespread apoptotic death in the granule layer of the deafferentated area. The time window of DNA fragmentation in granule layer was one to seven days after the "L-cut". Selective Purkinje cell deafferentation obtained by 3-acetylpyridine injection did not result in TUNEL staining in the cerebellar cortex. The current finding that mossy fiber axotomy induces granule cell apoptotic death points out for the first time the crucial role of afferent inputs in mature granule cell survival. Moreover, the in vivo lesional model described here may prove to be an useful tool for investigating cellular and molecular mechanisms of neuronal death triggered by deafferentation.
Afferent Pathways↗
Rapid diagnosis and management of thoracic aortic dissection and intramural haematoma: a prospective study of advantages of multiplane vs. biplane transoesophageal echocardiography.
AIMS: The purposes of this study were to compare the accuracy of multiplane vs. biplane transoesophageal echocardiography (TEE) in the diagnosis of aortic dissection and aortic intramural haematoma, and to test whether these techniques provide all the diagnostic information required to make management decisions. METHODS AND RESULTS: Fifty-eight consecutive patients with clinically suspected aortic dissection were studied with multiplane TEE; all cases who required surgery underwent intraoperative monitoring with multiplane TEE. The following multiplane TEE data were analysed: the angle between current and 0 degrees plane at which each view was obtained; the success rate in the evaluation of true and false lumen, entry tear, coronary artery involvement, aortic regurgitation, pericardial effusion. Advantages of multiplane over biplane TEE have been evaluated by the demonstration of usefulness of views obtained in planes other than 0 degrees-20 degrees or 70 degrees-110 degrees, assuming that with manipulation of a biplane probe a 20 degrees arc could be added to the conventional horizontal and vertical planes. On the basis of TEE findings, aortic dissection was confirmed in 36 cases (18 type A, 12 type B, six intramural haematoma). The specificity and sensitivity of TEE in terms of the presence or absence of aortic dissection or intramural haematoma were 100%. An additional clinical value of multiplane over biplane TEE in the evaluation of ascending aorta, aortic arch, entry tears and coronary artery involvement was demonstrated. All cases with type A aortic dissection or intramural haematoma involving the ascending aorta had an operation that was performed immediately after the diagnosis (hospital mortality, 13%). Patients with type B aortic dissection were treated medically; 25% of these cases were operated later (hospital mortality, 0%). CONCLUSIONS: Multiplane and biplane TEE have excellent and similar accuracies in the evaluation of aortic dissection and intramural haematoma. Multiplane TEE improves the visualization of coronary arteries, aortic arch and entry tears; it appears to be an ideal method as the sole diagnostic approach before surgery in type A aortic dissection.
Adult↗
Commentary on the workshop statement. Essentiality of and recommended dietary intake of Omega-6 and Omega-3 fatty acids.
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Diet↗
Fatty diets are unhealthy--even those based on monounsaturates.
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Dietary Fats↗
Production of live calves derived from embryonic stem-like cells aggregated with tetraploid embryos.
To date, cloned farm animals have been produced by nuclear transfer from embryonic, fetal, and adult cell types. However, mice completely derived from embryonic stem (ES) cells have been produced by aggregation with tetraploid embryos. The objective of the present study was to generate offspring completely derived from bovine ES-like cells. ES-like cells isolated from the inner cell mass of in vitro-produced embryos were aggregated with tetraploid bovine embryos generated by electrofusion at the 2-cell stage. A total of 77 embryo aggregates produced by coculture of two 8-cell-stage tetraploid embryos and a clump of ES-like cells were cultured in vitro. Twenty-eight of the aggregates developed to the blastocyst stage, and 12 of these were transferred to recipient cows. Six calves representing 2 singletons and 2 sets of twins were produced from the transfer of the chimeric embryos. Microsatellite analysis for the 6 calves demonstrated that one calf was chimeric in the hair roots and the another was chimeric in the liver. However, unfortunately, both of these calves died shortly after birth. Two of the placentae from the remaining pregnancies were also chimeric. These results indicate that the bovine ES-like cells used in these studies were able to contribute to development.
Animals↗
Inhibitory circuits in human dysplastic tissue.
PURPOSE: Different types of epilepsies and seizures depend on the nature and location of the primary disturbance and are presumably mediated by different physiopathological mechanisms. We immunocytochemically investigated possible changes in the inhibitory-aminobutyric acid (GABA)ergic system in specimens taken from four patients who underwent surgery for intractable epilepsy and presented two different types of focal cortical dysplasia in the temporal lobe. METHODS: The patients were selected on the basis of electroclinical, imaging, and routine neuropathological data: two had Taylor focal dysplasia, and two had non-Taylor dysplasia (microdysgenesia). The study was performed using antibodies against parvalbumin (PV), glutamic acid decarboxylase (GAD), and GABA-transporter 1 (GAT1). RESULTS: In the patients with Taylor dysplasia, laminar disorganization of the cortex was associated with the presence of giant neurons and ballooned cells; there was a reduced number of PV-positive neurons and terminals, the giant neurons were surrounded by clusters of PV- and GAD-positive terminals, and there was an overall reduction in GAT1. Despite the presence of cortical laminar disorganization, no giant or ballooned cells were found in the patients with non-Taylor microdysgenesia; there was a marked decrease in PV and GAD immunoreactive elements, with a patchy distribution of GAD and GAT1 immunoreactivity but no clustering of PV and GAD terminals. CONCLUSIONS: These results suggest that the two forms of cortical dysplasia are characterized by different and selective morphofunctional alterations in the GABAergic system.
Adult↗
Clinical ictal symptomatology and anatomical lesions: their relationships in severe partial epilepsy.
High-resolution imaging techniques can demonstrate anatomic alterations in most patients identified as candidates for surgical treatment of their partial epilepsy. The demonstration of an anatomic lesion is only one step in the presurgical diagnostic procedure, which includes video-EEG and, when necessary, video-stereo-EEG recordings of seizures. A review of the literature shows that the simple removal of the magnetic resonance imaging (MRI)-evident lesion ("lesion-ectomy") reduces but does not completely suppress seizures in a large percentage of patients, especially those with neuronal migration disorders. This phenomenon could, at least in part, be explained by preliminary data (in 33 patients) showing that less than 20% of seizures correspond to a well-localized, intralesional discharge in about 40% of stereo-EEG-investigated patients with at least one intralesional electrode. The authors illustrate some anatomo-electroclinical examples of intraindividual variability of the ictal symptomatology, raising the problem of the decision about the extent of the surgical removal. Recent histologic and immunohistochemical studies have demonstrated several kinds of structural alterations in the stereo-EEG-defined epileptogenic zone, not always overlapping with the MRI-visible lesion. This aspect can further explain some failures of MRI-guided lesionectomies. That relationships between "lesions" and epileptogenic zones may be variable is also suggested by reports of patients who present with multiple lesions (i.e., cavernous angiomas, Bourneville syndrome) and are cured by removal of only one of them.
Adult↗