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Biomedical subjects

L Almeida

Publications and source records attributed to L Almeida.

At least 19 recordsLinked to original sources
PubMed2006

Human metabolism of nebicapone (BIA 3-202), a novel catechol-o-methyltransferase inhibitor: characterization of in vitro glucuronidation.

Nebicapone (BIA 3-202; 1-[3,4-dihydroxy-5-nitrophenyl]-2-phenylethanone), a novel catechol-O-methyltransferase inhibitor, is mainly metabolized by glucuronidation. The purpose of this study was to characterize the major plasma metabolites of nebicapone following p.o. administration of nebicapone to healthy volunteers, and to determine the human UDP-glucuronosyltransferase (UGT) enzymes involved in nebicapone glucuronidation. Plasma samples were collected as part of a clinical trial at different time points postdose and were analyzed for nebicapone and its metabolites using a validated method consisting of a solid-phase extraction, followed by high-performance liquid chromatography/mass spectrometry detection. The primary metabolic pathways of nebicapone in humans involve mainly 3-O-glucuronidation, the major early metabolite, and 3-O-methylation, the predominant late metabolite. Of the nine commercially available recombinant UGT enzymes studied (UGT1A1, UGT1A3, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15), only UGT1A9 exhibited high nebicapone glucuronosyltransferase specific activity (24.3 +/- 1.3 nmol/mg protein/min). UGT1A6, UGT1A7, UGT1A8, UGT1A10, UGT2B7, and UGT2B15 exhibited low activity (0.1-1.1 nmol/mg protein/min), and UGT1A1 and UGT1A3 showed extremely low activities (less than 0.03 nmol/mg protein/min). The results show that nebicapone is mainly glucuronidated in humans and that multiple UGT enzymes are involved in this reaction.

Acetophenones↗
PubMed2006

Histological and scanning electron microscopy analyses of bone/implant interface using the novel Bonelike synthetic bone graft.

Synthetic bone grafts provide an alternative to autografts and allografts. Bonelike is a patented synthetic bone graft that mimics the mineral composition of bone. The aim of the present work was to assess the biological behavior of Bonelike graft in humans, before using the material in orthopedic applications of bone regeneration, for example, in opening wedge high tibial osteotomies for medial knee osteoarthritis. Bonelike granules were implanted in cortical bone of 11 patients undergoing osteotomies, and new bone formation, osteoconductive properties, and resorption characteristics of the granules were analyzed. The granules ranged from 500 to 1000 microm and were implanted in the lateral aspect of the tibia. The patients' mean age was 59 years (range 48 to 70 years); there were eight women and three men, all suffering from medial compartment osteoarthritis of the knee. At surgery, a 1 x 1 x 1-cm cortical defect was created 3 cm distal to the entry point of the screws, in line with the long axis of tibia. The implanted Bonelike graft sample was extracted for analysis during removal of the metallic prosthesis after implantation times of 6, 9, and 12 months. Radiological follow-up, scanning electron microscopy, histological analysis, and histomorphometric measurements were conducted on the retrieved samples to assess bone regeneration in the defect area. Osteoconductive capacity was demonstrated by extensive mature bone formation around the implanted granules and high levels of percentage bone-to-graft contact (from 67-84%). Bonelike acted as an excellent bioactive scaffold, allowing the migration, proliferation, and differentiation of bone cells on its surface, and therefore regeneration of the defects was achieved in a rapid, controlled manner. Our results suggest that Bonelike graft is an excellent candidate for orthopedic applications where rapid new bone formation is a fundamental requirement.

Aged↗
PubMed2005

Curative isosorbide-5-mononitrate treatment, in opposition to the beneficial preventive one, aggravates the prothrombotic and proconstrictor state in cyclosporine-induced hypertensive rats.

1. The aim of the present study was to evaluate the effect of preventive and curative isosorbide-5-mononitrate (Is-5-Mn) treatment on the development of hypertension, cGMP content, thromboxane (TX) A(2)/prostaglandin (PG) I2 balance, the peripheral serotonergic system, platelet activation, lipid peroxidation and plasma lipids in cyclosporine A (CsA)-induced hypertensive rats. 2. Control, CsA (5 mg/kg per day) and Is-5-Mn (150 mg/kg per day, b.i.d.) rat groups were treated orally over a period of 7 weeks. The preventive Is-5-Mn group (Is-5-Mn + CsA) was first treated for 2 weeks with Is-5-Mn, followed by 7 weeks with both drugs; the curative Is-5-Mn group (CsA + Is-5-Mn) was treated for a period of 7 weeks with CsA and with both drugs for an additional 5 weeks. The control group received oral vehicle. 3. Whereas in the group undergoing preventive treatment the CsA-induced increase in blood pressure (BP), compared with the control group, was avoided, in the group undergoing curative treatment, the increase in BP was even higher. The decreased arterial cGMP content in the CsA group was prevented and reverted when Is-Mn was administered either preventatively or curatively with CsA. Platelet TXA2 production, although unaffected in the Is-5-Mn + CsA group, was significantly higher in the CsA + Is-5-Mn group compared with the group receiving CsA alone. Furthermore, plasma TXA2 was reduced following preventive Is-5-Mn treatment, but was worsened in the group undergoing curative therapy. Aortic PGI2 synthesis was identical in all groups. Consequently, the TXA2/PGI2 ratio was only altered in the CsA + Is-5-Mn group, demonstrating a markedly higher value. In both groups treated simultaneously with CsA and Is-5-Mn, a higher platelet 5-hydroxytryptamine (5-HT) content was obtained compared with CsA treatment alone, but only preventive treatment with Is-5-Mn resulted in a significant reduction in plasma 5-HT. Changes in ADP and collagen-induced platelet aggregation paralleled those of plasma 5-HT and TXA2: the hyperaggregation profile of the CsA group, although partially prevented, was not reverted by simultaneous treatment with Is-5-Mn and CsA. Lipid peroxidation and lipid profile values also worsened in the CsA + Is-5-Mn group compared with the group administered CsA alone. 4. In conclusion, the beneficial effects of concomitant Is-5-Mn and CsA treatment were demonstrated when Is-5-Mn was administered preventatively because not only was arterial hypertension prevented, but platelet aggregation and plasma TXA2 and 5-HT levels were also reduced. In contrast, following curative treatment, the BP, platelet/vascular vasoconstrictor balance, lipid peroxidation and plasma lipids were aggravated, recommending a judicious evaluation of the impact of nitrate therapy throughout the period of its administration.

Animals↗
PubMed2005

Mustard allergy confirmed by double-blind placebo-controlled food challenges: clinical features and cross-reactivity with mugwort pollen and plant-derived foods.

BACKGROUND: Mustard IgE-mediated allergy is supposed to be a rare cause of food allergy, and its clinical features and cross-reactivities have not been fully elucidated. METHODS: A prospective study was carried out, recruiting mustard allergic patients, and paired control subjects. A clinical questionnaire was administered, and skin-prick tests (SPT) with panels of aeroallergens and foods, serum extraction for in vitro tests and double-blind placebo-controlled food challenges (DBPCFC) were performed. RESULTS: Thirty-eight mainly adult patients, with 10.5% reporting systemic anaphylaxis, were included in the study [age (mean +/- SD): 21.9 +/- 8.6 years]. DBPCFC were performed in 24 patients, being positive in 14 cases (58.3%). Patients with positive outcome showed significantly greater mustard SPT than those with negative outcome (8.2 +/- 3.7 vs 5.3 +/- 2.4 mm, P <0.05), and the receiver-operating characteristic (ROC) curve analysis yielded a cut-off value for mustard commercial SPT of 8 mm, with a specificity of 90% (95% CI, 55.5-98.3), and a sensitivity of 50% (95% CI, 23.1-76.9). A significant association between mustard hypersensitivity and mugwort pollen sensitization was found (97.4% of patients), with partial cross-reactivity demonstrated by UniCAP System inhibition assays. All patients showed sensitization to other members of Brassicaceae family, and cross-reactivity among them was also confirmed. Moreover, significant associations with nut (97.4%), leguminous (94.7%), corn (78.9%), and Rosaceae fruit (89.5%) sensitizations were also shown. Around 40% of these food sensitizations were symptomatic, including food-dependent exercise-induced anaphylaxis in six patients. CONCLUSIONS: Mustard allergy is a not-uncommon disorder that can induce severe reactions. Significant associations with mugwort pollinosis and several plant-derived food allergies are demonstrated, suggesting a new mustard-mugwort allergy syndrome. A relationship between this syndrome and food-dependent exercise-induced anaphylaxis is also reported.

Adolescent↗
PubMed2002

Circadian and seasonal variation of endogenous ubiquinone plasma level.

Coenzyme Q10 (CoQ10) or ubiquinone, a redox component of the mitochondrial electron transport chains, is a powerful antioxidant and membrane stabilizer that may prevent cellular damage during myocardial ischemia and reperfusion therapy. Coenzyme Q10 has been used primarily as an adjuvant therapy for some cardiomyopathies. However, one of the main problems in CoQ10 administration is the high variability of endogenous plasma and tissue levels, which seems to be dependent on several factors. This work explores temporal 24h and seasonal variation as well as gender and racial differences in endogenous plasma ubiquinone concentration. Coenzyme Q10 measurements (quantified by HPLC-UV) of 16 healthy volunteers were done during the daytime hours of activity beginning at 09:00h one day and ending at 09:00h the next day (13 different determinations) in two distinct months. April and October, of the year. A statistically significant circadian rhythm in plasma ubiquinone concentration that includes only the fundamental 24h component was demonstrated both in the April and October data. Furthermore, the time-point means of the ubiquinone concentration in the October study were invariably higher than those obtained in the April study. No statistically significant differences were found in CoQ10 concentration between male and female subjects, both in April and in October. In addition, racial differences were demonstrated; lower plasma ubiquinone levels were found in Caucasian compared to African subjects. However, the latter small group of subjects failed to demonstrate a circadian rhythm, neither in the April nor in the October analysis.

Adult↗
PubMed2001

The value of an immunoenzymatic test (enzyme-linked immunosorbent assay) for the diagnosis of strongyloidiasis in patients immunosuppressed by hematologic malignancies.

The diagnosis of strongyloidiasis relies upon the identification of the parasite in stool samples. In 1981, a serologic assay was developed, which was useful in the diagnosis of strongyloidiasis in the immunocompetent host. In the present study, we evaluated the enzyme-linked immunosorbent assay (ELISA) in patients with hematologic malignancies. Between April 1995 and December 1998, sera from 164 consecutive patients were tested for the presence of IgG antibody to Strongyloides stercoralis. Patient was considered uninfected after at least three negative stool examinations. The prevalence of strongyloidiasis was 13%. The underlying diseases were acute leukemia in 21% and lymphoma in 52% of the patients. The majority of the patients were receiving chemotherapy (93%) and steroids (76%). The sensitivity, specificity, and positive and negative predictive values were 68%, 89%, 48%, and 95%, respectively. The ELISA may be an excellent assay to rule out the diagnosis of strongyloidiasis in patients with hematologic malignancies.

Adult↗
PubMed2001

Long-term (four years) follow-up of patients with treated nocturnal hypertension assessed by ambulatory blood pressure monitoring.

STUDY OBJECTIVE: Nocturnal Hypertension (NH) is an independent risk factor for cardiovascular morbidity and mortality (M-M). However, an inappropriate decrease in diastolic BP during the night significantly increases morbidity. There are no prospective studies on the long-term consequences on M-M in treated NH. We accordingly studied M-M in 107 consecutive patients with treated NH, assessed by ambulatory blood pressure monitoring (ABPM), during a four-year follow-up. PATIENTS AND METHODS: From the initial 107 patients six died (5 from brain or cardiovascular causes). In 65 patients it was possible to repeat the ABPM during the follow-up period. They were hypertensive patients class I-II (JNC IV) 62 +/- 10 years old, 56 were male and were observed before and after starting treatment on a four-year follow-up period. We considered age, sex, body mass index, previous cerebral and cardiovascular accidents, type and number of drugs administered, smoking habits, plasma cholesterol, glycemia, and causal and ambulatory blood pressure monitoring (ABPM) (24 hr, 6 am-10 am, 10 pm-6 am and pulse pressure) before and after follow-up, dipper status and the period of follow-up. RESULTS: The patients whom died were older and had a significantly higher systolic blood pressure compared to the survivors. We considered two groups: with (A - n = 18) or without (B - n = 47) cerebral and cardiac morbidity. The A group had more previous cerebral and cardiovascular accidents (p = 0.05), a more intensive treatment (p = 0.02), and a greater fall in diastolic blood pressure (DBP) during the night in both absolute and percentage numbers, after treatment, than the B group. However, after regression analysis, the only independent risk marker differentiating between the two groups was the percentage fall in the DBP after treatment (dipper phenomenon) (p = 0.01). CONCLUSIONS: In 65 treated hypertensive (NH) patients assessed by ABPM before and after treatment (four-year follow-up) we identified a group with cerebral and cardiovascular morbidity. These patients, in contrast with another group with no morbidity, had more previous cerebral and cardiovascular accidents, they were more intensively treated, and they had a greater fall in diastolic blood pressure after therapy (absolute and percentage values). However, after regression analysis the diastolic nocturnal blood pressure dipper phenomenon after treatment was the only risk marker associated with morbidity. In such cases it is possible that treatment guided by ABPM can decrease morbidity.

Aged↗
PubMed2001

[Is ambulatory blood pressure monitoring reliable in hypertensive patients with atrial fibrillation?].

Atrial fibrillation (AF) is commonly seen in patients (pts) with systemic hypertension. They are usually excluded from ambulatory blood pressure monitoring (ABPM) because its accuracy is unknown. The aim of our study was to determine if ABPM can be used to assess 24 hour BP in pts with AF. We included hypertensive pts with chronic (> 6 months) AF, controlled heart rate (60-100 c.p.m), under therapy and also hypertensive pts in sinus rhythm (control group--CG). They were submitted to 24 hour ABPM (Spacelabs 90207). Manual BP with a standard mercury sphygmomanometer was taken during 3 visits (office BP) and on the day of ambulatory monitoring. Simultaneous measurements with a T-Tube were also performed. Thirty pts with chronic AF (63% males), mean age 73 +/- 8 years (52-85) and 18 pts in sinus rhythm (CG) were studied. The age, gender, office BP, ambulatory BP and proportion of successful measurements was similar in the 2 groups. In CG systolic and diastolic office BP did not differ from day ambulatory BP (148 +/- 14/84 +/- 7 vs 138 +/- 18/76 +/- 11 mmHg) and the same was seen in pts in AF (table). In this group, only the systolic BP taken immediately before the ambulatory device was put on, was significantly different from day ambulatory BP (148 +/- 21 vs 137 +/- 19 mmHg, p = 0.04). The proportion of successful measurements in AF group was 94 +/- 8 (65-98) with 93% > 80%. In 64 simultaneous measurements the differences were 6 +/- 5 and 5 +/- 5 mmHg for systolic and diastolic BP. Casual and ambulatory heart rate was also similar in the two groups (76 +/- 7/76 +/- 12--AF group; 78 +/- 10/78 +/- 8--control group). In conclusion, this study demonstrates that ABPM can be used to assess BP in patients with atrial fibrillation. There was a high percentage of successful recordings (93%). As in patients in sinus rhythm, there was no significantly difference in mean office blood pressure and daytime ambulatory blood pressure.

Aged↗
PubMed2000

Diversity of cyanobacterial hydrogenases, a molecular approach.

In an effort to elucidate the diversity of cyanobacterial hydrogenases, we used a molecular approach. Filamentous strains from a broad range of sources were screened for the presence of hup (uptake hydrogenase), xisC (rearrangement within hupL), and hox (bidirectional hydrogenase) genes. As expected, an uptake hydrogenase seems to be present in all N(2)-fixing cyanobacteria. On the other hand, no evidence was found for the presence of a conventional bidirectional enzyme in several strains. Similarly, the presence of xisC is not a characteristic shared by all the heterocyst-forming cyanobacteria. Although tempting, it is not possible to establish a correlation between the presence/absence of the bidirectional hydrogenase and the occurrence of xisC. The natural molecular variation of hydrogenases in cyanobacteria is certainly a field to explore, both to understand the physiological functions of the respective enzymes and to identify a genetic background to be used when constructing a strain for photobiological H(2) production in a bioreactor.

Bacterial Proteins↗
PubMed2000

Oxidized LDLs alter the activity of the ubiquitin-proteasome pathway: potential role in oxidized LDL-induced apoptosis.

Oxidized low-density lipoproteins (oxLDL) play a role in the genesis of atherosclerosis. OxLDL are able to induce apoptosis of vascular cells, which is potentially involved in the formation of the necrotic center of atherosclerotic lesions, plaque rupture, and subsequent thrombotic events. Because oxLDL may induce structural modifications of cell protein and altered proteins may impair cell viability, the present work aimed to evaluate the extent of protein alterations, the degradation of modified proteins through the ubiquitin-proteasome system (a major degradative pathway for altered and oxidatively modified proteins) and their role during apoptosis induced by oxLDL. This paper reports the following: 1) oxLDL induce derivatization of cell proteins by 4-hydroxynonenal (4-HNE) and ubiquitination. 2) Toxic concentrations of oxLDL elicit a biphasic effect on proteasome activity. An early and transient activation of endogenous proteolysis is followed rapidly by a subsequent decay (resulting probably from the 26S proteasome inhibition) and followed later by the inhibition of the 20S proteasome (as assessed by inhibition of sLLVY-MCA hydrolysis). 3) Specific inhibitors of proteasome (lactacystin and proteasome inhibitor I) potentiated considerably the toxicity of oxLDL (nontoxic doses of oxLDL became severely toxic). The defect of the ubiquitination pathway (in temperature-sensitive mutants) also potentiated the toxicity of oxLDL. This suggests that the ubiquitin-proteasome pathway plays a role in the cellular defenses against oxLDL-induced toxicity. 4) Dinitrophenylhydrazine (DNPH), an aldehyde reagent, prevented both the oxLDL-induced derivatization of cell proteins and subsequent cytotoxicity. Altogether, the reported data suggest that both derivatization of cell proteins (by 4-HNE and other oxidized lipids) and inhibition of the proteasome pathway are involved in the mechanism of oxLDL-induced apoptosis.

3T3 Cells↗
PubMed1999

[Arterial hypertension difficult to control in the elderly patient. The significance of the "white coat effect"].

OBJECTIVE: Previous studies have revealed a high prevalence of white coat effect among treated hypertensive patients. The difference between clinic and ambulatory blood pressure seems to be more pronounced in older patients. This abnormal rise in blood pressure BP in treated hypertensive patients can lead to a misdiagnosis of refractory hypertension. Clinicians may increase the dosage of antihypertensive drugs or add further medication, increasing costs and producing harmful secondary effects. Our aim was to evaluate the discrepancy between clinic and ambulatory blood pressure in hypertensive patients on adequate antihypertensive treatment and to analyse the magnitude of the white coat effect and its relationship with age, gender, clinic blood pressure and cardiovascular or cerebrovascular events. POPULATION AND METHODS: We included 50 consecutive moderate/severe hypertensive patients, 58% female, mean age 68 +/- 10 years (48-88), clinic blood pressure (3 visits) > 160/90 mm Hg, on antihypertensive adequate treatment > 2 months with good compliance and without pseudohypertension. The patients were submitted to clinical evaluation (risk score), clinic blood pressure and heart rate, electrocardiogram and ambulatory blood pressure monitoring (Spacelabs 90,207). Systolic and diastolic 24 hour, daytime, night-time blood pressure and heart rate were recorded. We considered elderly patients above 60 years of age (80%). We defined white coat effect as the difference between systolic clinic blood pressure and daytime systolic blood pressure BP > 20 mm Hg or the difference between diastolic clinic blood pressure and daytime diastolic blood pressure > 10 mm Hg and severe white coat effect as systolic clinic blood pressure--daytime systolic blood pressure > 40 mm Hg or diastolic clinic blood pressure--daytime diastolic blood pressure > 20 mm Hg. The patients were asked to take blood pressure measurements out of hospital (at home or by a nurse). The majority of them performed an echocardiogram examination. RESULTS: Clinic blood pressure was significantly different from daytime ambulatory blood pressure (189 +/- 19/96 +/- 13 vs 139 +/- 18/78 +/- 10 mm Hg, p < 0.005). The magnitude of white coat effect was 50 +/- 17 (8-84) mm Hg for systolic blood pressure and 18 +/- 11 (-9 +/- 41) mm Hg for diastolic blood pressure. A marked white coat effect (> 40 mm Hg) was observed in 78% of our hypertensive patients. In elderly people (> 60 years), this difference was greater (50 +/- 15 vs 45 +/- 21 mm Hg) though not significantly. We did not find significant differences between sexes (males 54 +/- 16 mm Hg vs 48 +/- 17 mm Hg). In 66% of these patients, ambulatory blood pressure monitoring showed daytime blood pressure values < 140/90 mm Hg, therefore refractory hypertension was excluded. In 8 patients (18%) there was a previous history of ischemic cardiovascular or cerebrovascular disease and all of them had a marked difference between systolic clinic and daytime blood pressure (> 40 mm Hg). Blood pressure measurements performed out of hospital did not help clinicians to identify this phenomena as only 16% were similar (+/- 5 mm Hg) to ambulatory daytime values. CONCLUSIONS: Some hypertensive patients, on adequate antihypertensive treatment, have a significant difference between clinic blood pressure and ambulatory blood pressure measurements. This difference (White Coat Effect) is greater in elderly patients and in men (NS). Although clinic blood pressure values were significantly increased, the majority of these patients have controlled blood pressure on ambulatory monitoring. In this population, ambulatory blood pressure monitoring was of great value to identify a misdiagnosis of refractory hypertension, which could lead to improper decisions in the therapeutic management of elderly patients (increasing treatment) and compromise cerebrovascular or coronary circulation.

Age Factors↗
PubMed1998

Cholesteryl ester hydroperoxide formation in myoglobin-catalyzed low density lipoprotein oxidation: concerted antioxidant activity of caffeic and p-coumaric acids with ascorbate.

Two diet-derived phenolic acids, caffeic and p-coumaric acids, interplayed with ascorbate in the protection of low density lipoproteins (LDL) from oxidation promoted by ferrylmyoglobin. Ferrylmyoglobin, a two-electron oxidation product from the reaction of metmyoglobin and H2O2, was able to oxidize LDL, degrading free cholesterol and cholesteryl esters. Upon exposure to ferrylmyoglobin, LDL became rapidly depleted of cholesteryl arachidonate and linoleate, which turn into the corresponding hydroperoxides. Cholesteryl oleate and cholesterol were, comparatively, more resistant to oxidation. Caffeic (2 microM) and p-coumaric (12 microM) acids efficiently delayed oxidations, as reflected by an increase in the lag times required for linoleate hydroperoxide and 7-ketocholesterol formation as well as for cholesteryl linoleate consumption. At the same concentration, ascorbate, a standard water-soluble antioxidant, was less efficient than the phenolic acids. Additionally, phenolic acids afforded a protection to LDL that, conversely to ascorbate, extends along the time, as inferred from the high levels of cholesteryl linoleate and cholesteryl arachidonate left after 22 hr of oxidation challenging. Significantly, the coincubation of LDL with ascorbate and each of the phenolic acids resulted in a synergistic protection from oxidation. This was inferred from the lag phases of cholesteryl linoleate hydroperoxide (the major peroxide found in LDL) formation in the presence of mixtures of ascorbate with phenolic acids longer than the sum of individual lag phases of ascorbate and the phenolic acids. A similar description could be drawn for the accumulation of a late product of oxidation, 7-ketocholesterol. It is concluded that ferrylmyoglobin induces a typical pattern of LDL lipid peroxidation, the oxidation rate of cholesteryl esters being a function of unsaturation; furthermore, there is a synergistic antioxidant activity of diet-derived phenolic acids with ascorbate in the protection of LDL from oxidation, a finding of putative physiological relevance.

Animals↗
PubMed1998

Effect of dietary phenolic compounds on apoptosis of human cultured endothelial cells induced by oxidized LDL.

1. Oxidized low density lipoproteins (LDL) are toxic to cultured endothelial cells. Mildly oxidized LDL, characterized by relatively low levels of TBARS and only minor modifications of apoB, were obtained by using 2 experimental model systems of oxidation, namely oxidation by u.v. radiation or ferrylmyoglobin (a two electron oxidation product from the reaction of metmyoglobin with H2O2). 2. Toxic concentrations of mildly oxidized LDL induce apoptosis (programmed cell death) of cultured endothelial cells, as shown by typical morphological features, by the in situ TUNEL procedure and by DNA fragmentation revealed on gel electrophoresis. This apoptosis is calcium-dependent and subsequent to the intense and sustained cytosolic [Ca2+]i peak elicited by oxidized LDL. 3. Five naturally occurring phenolic compounds present in food and beverages were able to prevent, in a concentration-dependent manner, the apoptosis of endothelial cells induced by oxidized LDL. Among the compounds tested, caffeic acid was the most effective. Under the conditions used, the protective effect of caffeic acid (IC50 8.3+/-2.1 micromol l[-1]) in the prevention of apoptosis induced by oxidized LDL was significantly higher than that of the other compounds tested (IC50s were 12.4+/-3.2, 14.1+/-4.1, 20.4+/-4.4 and 72.6+/-9.2 micromol l(-1) for ferulic, protocatechuic, ellagic and p-coumaric acids, respectively). 4. The anti-apoptotic effect of caffeic acid results from the addition of two effects, (i) the antioxidant effect which prevents LDL oxidation and subsequent toxicity ('indirect' protective effect); (ii) a 'direct' cytoprotective effect, acting at the cellular level. 5. Effective concentrations of caffeic acid acted at the cellular level by blocking the intense and sustained cytosolic [Ca2+]i rise elicited by oxidized LDL. 6. In conclusion, phenolic acids (caffeic and ferulic acids being the most potent of the compounds tested under the conditions used) exhibit a potent cytoprotective effect of cultured endothelial cells against oxidized LDL. In addition to antioxidant effect delaying LDL oxidation, caffeic acid acts as a cytoprotective agent, probably by blocking the intracellular signalling triggered by oxidized LDL and culminating in the sustained calcium rise which is involved in oxidized LDL-induced apoptosis.

Antioxidants↗
PubMed1998

Influence of 0.1 or 0.2% cholesterol-enriched diets on the induction of atherosclerosis and aorta reactivity in vitro.

Current knowledge of atherogenesis is largely based on animal models of hypercholesterolemia, which rarely show changes similar to the lesions described in humans. We studied the influence of two low cholesterol-enriched diets on the development of anatomopathologic lesions and on the reactivity of the isolated aorta in rabbits. Compared with controls (rabbits fed a normal diet), a 0.1% cholesterol-enriched diet over a 6- or 9-month period produced increases of the 5-hydroxytryptamine (5-HT)-induced contractile responses, as well as a decreases in acetylcholine (ACh)-induced relaxing response (endothelium-dependent, through the production of NO). Noradrenaline (NA)-induced contractions and relaxations elicited by sodium nitroprusside (SNP; endothelium independent) were not significantly modified. Because at 6 months, significant anatomopathologic intimal early lesions were not found, functional endothelial changes can explain such findings. There was a defect in NO synthesis, release, or diffusion; 5 HT, but not NA, may be responsible for inducing NO production. In 0.2% cholesterol-fed rabbits at 4 and 12 weeks, increases of 5-HT- and NA-induced contractile responses were found. In both cases, there was a decrease of ACh-induced relaxing effect, whereas responses to SNP remained unchanged. Intimal early and advanced lesions were present at both the 4- and 12-week periods. These data suggest abnormalities of the NO system. The effects obtained with NA may be explained by a possible decrease of catechol-O-methyltransferase (COMT) or monoamine oxidase (MAO) activities or both or by decreased amine uptake. The extent to which NA may induce NO production is small, because changes in NA-induced contractions are verified only in the presence of significant alterations in the endothelium. The use of a 0.2% cholesterol diet for a short time may induce atherosclerotic lesions, whereas the 0.1% cholesterol diet for a 9-month period, besides being closer to the human diet, allows the detection of functional abnormalities before the evidence of structural lesions.

Animals↗