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Biomedical subjects

C Napoli

Publications and source records attributed to C Napoli.

At least 73 records · Page 4Linked to original sources
PubMed1999

"Warm-up" phenomenon detected by electrocardiographic ambulatory monitoring in adult and older patients.

OBJECTIVE: Inducing tolerance to myocardial ischemia by repeated brief episodes of ischemia has been called "ischemic preconditioning." "Warm-up" phenomenon refers to patients with coronary heart disease improving performance after a first exertion and may represent a clinical counterpart to ischemic preconditioning. The goal of this study was to assess whether the severity of myocardial ischemia would be attenuated by two repeated walking-induced ischemic episodes in adult and older patients. SUBJECTS: Thirty-eight adults (51 +/- 5 years) and 39 older patients (76 +/- 4 years) with stable angina and angiographic evidence of coronary stenosis. MEASUREMENTS: Holter monitoring was performed in adult and older patients walking on two consecutive occasions, with a 5-minute rest between walks, a distance known to have previously caused myocardial ischemia. RESULTS: Computer-assisted analysis recorded by ambulatory Holter monitoring revealed that the mean maximal ST-segment depression (P < .001) and ischemia duration decreased (P < .001), whereas the ischemic threshold increased (P < .001), from the first to the second walk in the adult but not in the older group. CONCLUSIONS: Myocardial ischemia is attenuated and ischemic threshold is increased between two brief ischemic episodes in adult but not in older patients. These results indicate that the "warm-up" phenomenon, involved in increasing myocardial ischemic tolerance, is absent in the aging heart.

Aged↗
PubMed1999

1,4-Dihydropyridine calcium channel blockers inhibit plasma and LDL oxidation and formation of oxidation-specific epitopes in the arterial wall and prolong survival in stroke-prone spontaneously hypertensive rats.

BACKGROUND AND PURPOSE: Calcium-channel blockers (CCBs) reduce systolic blood pressure and stroke-related mortality in stroke-prone spontaneously hypertensive rats (SPSHR). Brain ischemia is associated with loss of intracellular antioxidants. Increased formation of oxygen radicals and oxidation of LDL may enhance arterial vasoconstriction by various mechanisms. CCBs that also exert antioxidative properties in vitro may therefore be particularly useful. To investigate such antioxidant effects in vivo, we determined several parameters of LDL oxidation in SPSHR treated with two 1,4-dihydropyridine-type (1,4-DHP) CCBs of different lipophilic properties and compared them with antioxidant-treated and untreated controls. We also tested whether these drugs decrease the formation of oxidation-specific epitopes in arteries. METHODS: Five groups of 9 to 14 SPSHR each (aged 8 weeks) were treated with 80 mg/kg body wt per day nifedipine, 1 mg or 0.3 mg/kg body wt per day lacidipine, vitamin E (100 IU/d), or carrier for 5 weeks. A group of Wistar-Kyoto rats was used as normotensive control. Plasma samples were taken, and LDL was isolated by ultracentrifugation. Then LDL was exposed to oxygen radicals generated by xanthine/xanthine oxidase reaction (2 mmol/L xanthine+100 mU/mL xanthine oxidase), and several parameters of oxidation were determined. The presence of native apolipoprotein B and oxidation-specific epitopes in the carotid and middle cerebral arteries was determined immunocytochemically. RESULTS: 1,4-DHP CCBs completely prevented mortality. Normotensive Wistar-Kyoto rats showed less oxidation than control SPSHR. Plasma lipoperoxide levels were 0.87+/-0.27 micromol/L in control SPSHR, 0.69+/-0.19 and 0.63+/-0.20 micromol/L in the groups treated with 0.3 and 1 mg lacidipine, respectively, and 0.68+/-0.23 micromol/L in nifedipine-treated animals (P<0.05 versus control SPSHR for all values). Both CCBs significantly decreased formation of conjugated dienes and prolonged the lag time in LDL exposed to oxygen radicals. Similarly, lipoperoxides and malondialdehyde were significantly reduced (P<0.05). Reduced relative electrophoretic mobility and increased trinitrobenzenesulfonic acid reactivity of LDL from treated rats (P<0.01) also indicated that fewer lysine residues of apolipoprotein B were oxidatively modified in the presence of 1,4-DHP CCBs. Finally, these drugs reduced the intimal presence of apolipoprotein B and oxidized LDL (oxidation-specific epitopes) in carotid and middle cerebral arteries. CONCLUSIONS: In the SPSHR model, 1,4-DHP CCBs reduce plasma and LDL oxidation and formation of oxidation-specific epitopes and prolong survival independently of blood pressure modifications. Our results support the concept that the in vivo protective effect of these drugs on cerebral ischemia and stroke may in part result from inhibition of oxidative processes.

Animals↗
PubMed1999

Evidence of exercise-induced myocardial ischemia in patients with primary aldosteronism: the Cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study.

BACKGROUND: Primary aldosteronism (PA) is a disease associated with hypersecretion of aldosterone caused by an aldosterone-producing adrenal adenoma, bilateral adrenal hyperplasia, and, although rarely, by adrenal carcinoma. Arterial hypertension induces several cardiovascular alterations that yield a high cardiovascular risk. It has been shown that reduced myocardial perfusion at rest, assessed by thallium-201 myocardial scintigraphy, was greater in PA than in essential hypertension (EH). However, it is still unknown whether reduced myocardial perfusion at rest and/or regional function abnormalities are present during exercise-induced myocardial stress. PURPOSE: We addressed the impact of PA on myocardial ischemia and sought to identify signs of exercise-induced myocardial ischemia (assessed by MIBI-SPECT and echocardiography) in patients with PA compared to patients with EH. Patients with consistent signs of myocardial ischemia on all of the tests were studied by coronary arteriography. PATIENTS: We studied 72 patients with PA and an age/sex-matched group of 72 patients with EH enrolled in the cross-sectional Primary Aldosteronism and Heart Italian Multicenter Study (PAHIMS). METHODS: Regional function was detected from echocardiographic measurement of wall motion done at baseline and immediately after exercise. Myocardial perfusion was evaluated by SPECT imaging after injecting 99mTc-MIBI with the same-day protocol using the rest-stress sequence. RESULTS: Although the conditions of arterial pressure, duration of hypertension, and target organ damage were equivalent, the patients with PA had greater incidence of both reversible perfusion defects and abnormalities of regional function. Moreover, multiple regression analysis showed that the high plasma aldosterone level was highly predictive for SPECT ischemic score and wall motion index, suggesting that PA contributes to cardiovascular risk over and above that associated with ventricular hypertrophy. Exercise-induced myocardial ischemia in PA was not segmental but widely distributed suggesting that this phenomenon was not related to abnormal coronary perfusion. Accordingly, of the 38 patients with PA who underwent coronarography, there was no presence of significant coronary atherosclerotic lesions in 30 (78.9%) of the patients. CONCLUSIONS: The PAHIMS observed more exercise-induced moderate myocardial ischemic defects (co-detected by SPECT and echocardiograms and not segmental but widely allocated) in patients with PA than in patients with EH. This phenomenon occurred in a greater percentage of patients with PA without significant coronary lesions (78.95%, n = 38), which supports the possible presence of small-vessel intramyocardial disease.

Adult↗
PubMed1999

Inhibition of VCAM-1 expression in the arterial wall is shared by structurally different antioxidants that reduce early atherosclerosis in NZW rabbits.

We previously established that probucol decreases basal expression of VCAM-1 in the aorta of WHHL rabbits and inhibits the up-regulation of VCAM-1 expression that normally accompanies atherogenesis. To determine whether this effect is shared by other antioxidants in vivo, we now investigated whether a structurally unrelated antioxidant, vitamin E, also inhibits arterial VCAM-1 expression and whether the degree of VCAM-1 inhibition correlates with the reduction of atherosclerosis or the antioxidant protection of LDL. Atherogenesis and VCAM-1 mRNA and protein were determined in four groups of NZW rabbits (n = 6;-8) fed 0.5% cholesterol alone or supplemented with 0.1% vitamin E, a low dose (0.04;-0.075%) of probucol yielding the same degree of antioxidant protection of plasma LDL as vitamin E, or a high dose (0.5%) of probucol, and in normocholesterolemic rabbits. After 81 days, extensive atherosclerosis and a greater than 4-fold up-regulation of VCAM-1 mRNA was seen in rabbits on high cholesterol diet, mostly in the intima. Treatment with vitamin E, high-dose probucol, and low-dose probucol significantly decreased VCAM-1 mRNA by 49.0, 74.9, and 57. 5%, respectively, and reduced atherosclerosis in adjacent segments of the thoracic aorta to a similar degree as reported by previous studies. Immunocytochemistry confirmed that lesions of antioxidant-treated animals also contained less VCAM-1 protein. Neither the degree of VCAM-1 inhibition nor the extent of atherosclerosis correlated with the degree of antioxidant protection of plasma LDL.In summary, treatment with structurally unrelated antioxidants conveyed different degrees of antioxidant protection to plasma LDL but significantly reduced VCAM-1 expression in vivo and inhibited atherogenesis. This is consistent with the assumption that antiatherogenic effects of antioxidants may in part be mediated by interference with oxidation-dependent intracellular signaling.

Animals↗
PubMed1999

Marked variation of thymidylate synthase and folylpolyglutamate synthetase gene expression in human colorectal tumors.

Patients with advanced colorectal cancer are currently being treated with 5-fluorouracil (5-FU)-based chemotherapy. A growing number of patients with resectable disease receive adjuvant therapy with 5-FU/levamisole (LEV) or 5-FU/folinic acid (LV). However, many patients still fail on these treatments, due to occurrence of natural or acquired tumor resistance. Among clinically relevant mechanisms of resistance to fluoropyrimidines, increased expression of thymidylate synthase (TS) has been emphasized. Another potentially relevant mechanism involves a decrease in folylpolyglutamate synthetase (FPGS) expression. To establish the value of these genes as prognostic factors and predictors of the outcome of 5-FU-based chemotherapy in colorectal cancer, we measured their expression in colorectal tumors from patients undergoing surgery and postoperative chemotherapy and compared it with that in normal colonic mucosa. This was done by a semi quantitative, nonradioisotopic polymerase chain reaction (PCR) method using beta-actin as an internal standard and expressed as a TS/beta-actin or a FPGS/beta-actin mRNA ratio. In tumor samples from 21 colorectal cancer patients, TS gene expression varied 118-fold. The median TS/beta-actin ratio was, in fact, 41.36 x 10(-3) (range 2.49 x 10(-3) to 294.54 x 10(-3)). Little variation in TS gene expression was observed in corresponding normal colic mucosa; the TS/beta-actin gene ratio was lower (median 26.16 x 10(-3); range 8.49 x 10(-3) to 69.49 x 10(-3)). Among tumor explants from 20 patients, FPGS expression varied over 161-fold. A similar marked variation was also observed in normal colonic mucosal samples (over 185-fold). Overall and disease-free survival data suggest an inverse association between the level of tumor TS and FPGS expression and clinical prognosis. The availability of this sensitive and accurate assay for gene expression should now make it possible to extend these laboratory/clinical correlations to larger populations.

Adult↗
PubMed1998

New-onset angina preceding acute myocardial infarction is associated with improved contractile recovery after thrombolysis.

BACKGROUND: Ischaemic preconditioning reduces myocardial infarct size in animal models. Clinical data suggest that episodes of angina immediately before acute myocardial infarction may be associated with smaller infarct size in man. However, it is unclear whether ischaemic episodes preceding acute myocardial infarction also affect contractile recovery in patients. OBJECTIVE: In this study we investigated the recovery of regional myocardial function after thrombolysis in two groups of patients at their first Q-wave acute myocardial infarction; in one group (n = 42) myocardial infarction occurred unheralded, whereas patients of the second group (n = 48) had experienced new-onset angina in the 48 h that preceded infarction. Echocardiographic analysis of myocardial regional function in the infarct area was done at 2, 24 and 72 h after thrombolysis, and at 1 week, and 1 and 3 months follow-up. RESULTS: Peak level of MB-creatine kinase was significantly lower in patients with new-onset angina (96 +/- 47 as compared with 221 +/- 108 IU.l-1, P < 0.01), as was the area under the MB-creatine kinase curve (1321 +/- 876 as compared to 3879 +/- 1555 U.l-1/36 h, P < 0.01). Hypokinetic segments were fewer in patients with pre-infarction angina. Similarly, wall motion score improved significantly earlier in patients who had new-onset angina before acute myocardial infarction. Thus, contractile recovery was more rapid in patients with previous angina than in those in whom infarction occurred unheralded. Complications during the in-hospital outcome and other variables considered during the 4-week follow-up were similar between groups. CONCLUSIONS: Patients who experienced new-onset angina before acute myocardial infarction showed better recovery of regional function after thrombolysis. Our study supports the hypothesis that brief periods of ischaemia immediately before myocardial infarction may precondition the human heart, thus improving contractile recovery.

Angina Pectoris↗
PubMed1998

Age-related effects of acidosis in isolated cardiac muscle.

Acidosis is associated with myocardial ischemia and several reports indicate the greater vulnerability of the aged heart to ischemic dysfunction. We investigated the effects of hypercapnic acidosis on isolated heart (n = 14) and papillary muscle (n = 10) from adult and senescent rats. Acidosis (pH from 7.36 to 6.91) induced a decrease in left ventricular developed pressure together with an increase in left ventricular end-diastolic pressure, but was significantly more evident in senescent than in adult hearts (p < .01). The return to normal pH induced a further increase in the end-diastolic pressure parallel to the development of arrhythmias that were greater in senescent than in adult hearts. In isolated papillary muscle, acidosis confirmed its greater negative inotropic effect on senescent than adult muscles (p < .01), while intracellular sodium activity (aNai) increased to a similar extent in both adult and senescent papillary muscles (p = NS). 5-(N,N-dimethyl)-amiloride hydrochloride (DMA), a specific inhibitor of Na+/H+ exchanger, produced similar modification of tension and aNai in both adult and senescent muscles. When DMA was superfused in acidotic solution, the contractility was markedly compromised in senescent than in adult muscles (p < .01), but the aNai modifications were similar in adult and senescent muscles (p = NS). Our results show that acidosis induced a greater reduction of contractility in senescent than in adult hearts. The similarity of contractility during DMA administration between adult and senescent muscle and of modifications of aNai suggests that depression of contractility with acidosis may be related to pathophysiologic mechanisms other than the Na+/H+ exchanger.

Acidosis↗
PubMed1998

Effects of vitamin E and HMG-CoA reductase inhibition on cholesteryl ester transfer protein and lecithin-cholesterol acyltransferase in hypercholesterolemia.

BACKGROUND: The enzyme lecithin-cholesterol acyl transferase (LCAT) esterifies free cholesterol on high-density lipoprotein (HDL) and the cholesteryl ester transfer protein (CETP) transfers cholesteryl ester to very-low-density lipoprotein (VLDL) and low-density lipoproteins (LDL). Using statins, contradictory findings have been made regarding CETP activity in normolipidemic individuals and in those with familial dysbetalipoproteinemia. In contrast, LCAT activity appears to be unaffected by simvastatin. Antioxidants have also been proposed for the use of anti-atherosclerotic treatment, because the oxidation of LDL may have a key role in the pathophysiology of atherogenesis. OBJECTIVE: To investigate, in hypercholesterolemic patients, whether a combination of pravastatin with the antioxidant, vitamin E, has greater effects on the activity of CETP and of LCAT than does pravastatin alone. METHODS: This placebo-diet-controlled multicenter trial included 220 hypercholesterolemic patients who were assigned randomly to groups to receive: diet and 20-40 mg pravastatin (n = 52), diet and alpha-tocopherol (n = 60), or diet associated with placebo (n = 52). Plasma LCAT activity was determined using excess exogenous substrate, containing [3H]cholesterol. Plasma CETP activity was measured in the supernatant fraction after precipitation of endogenous apo B-containing lipoproteins with phosphotungstate-Mg2+. The exchange of cholesteryl esters between [14C]cholesteryl ester-labeled LDL and unlabeled HDL was measured during a 16-h incubation, while LCAT was inhibited. RESULTS: The addition of pravastatin to the diet induced a significant decrease in plasma CETP activity (P < 0.05); this effect was less evident in the group cotreated with vitamin E. For the first time, it was shown that CETP concentrations increased significantly after vitamin E alone (P < 0.05). No significant differences in the plasma activity of LCAT were observed among the groups. CONCLUSIONS: Pravastatin reduced CETP activity, but not that of LCAT. Addition of vitamin E prevented the decrease in CETP activity and had no effect on LCAT activity. The mechanism responsible for these effects is unknown, but could involve the prevention of radical-induced damage to CETP by vitamin E.

Antioxidants↗
PubMed1998

Congestive heart failure and cognitive impairment in an older population. Osservatorio Geriatrico Campano Study Group.

OBJECTIVE: Congestive heart failure (CHF) is potentially preventable, and the identification of modifiable risk factors for cognitive impairment (CI) for older persons is a very important issue. We examined the cross-sectional relationship between CHF and CI in an older population. DESIGN: A cross-sectional survey. SETTING AND PARTICIPANTS: A total of 1339 subjects aged 65 and older were selected from the electoral rolls of Campania, a region of southern Italy. MEASUREMENTS: Sociodemographic characteristics were recorded, as was the presence of cardiovascular diseases, including CHF classified according to the New York Heart Association (NYHA) guidelines for disease severity; CI evaluated by means of the Mini-Mental State Examination (MMSE), with a score of <24 indicating impairment; geriatric depression scale (GDS) rating; blood pressure (BP); and heart rate (HR). RESULTS: The final sample numbered 1075; 172 subjects were excluded because of neurological disorders and psychotropic therapy, and 92 were excluded because their BP, HR, or cognitive examination was not recorded. Prevalence of CHF was 8.2%, and 23.0% of subjects scored <24 on the MMSE. The prevalence of CHF in subjects with an MMSE score of <24 and > or =24 was 20.2% and 4.6%, respectively (P < .001). Logistic regression analysis showed that CHF was associated independently with CI by sex, age, educational level, GDS, diabetes, hypertension, alcohol consumption, smoking, atrial fibrillation, systolic and diastolic BP, and HR. The risk of CI was 1.96-fold greater in subjects with CHF (odds ratio: 1.96; 95% confidence interval: 1.07-3.58; P < .028). Systolic BP decrease was correlated negatively with NYHA classes only in subjects with CI (r = -0.981; P < .020), whereas HR increase was correlated positively with NYHA classes only in subjects without CI (r = 0.985; P < .015). CONCLUSIONS: In our population, CHF is associated with CI in subjects aged 65 years and older. Systolic BP reduction and the lack of HR increase, related to NYHA classes, might characterize cognitively impaired subjects with CHF.

Aged↗
PubMed1997

Fatty streak formation occurs in human fetal aortas and is greatly enhanced by maternal hypercholesterolemia. Intimal accumulation of low density lipoprotein and its oxidation precede monocyte recruitment into early atherosclerotic lesions.

To determine whether oxidized LDL enhances atherogenesis by promoting monocyte recruitment into the vascular intima, we investigated whether LDL accumulation and oxidation precede intimal accumulation of monocytes in human fetal aortas (from spontaneous abortions and premature newborns who died within 12 h; fetal age 6.2+/-1.3 mo). For this purpose, a systematic assessment of fatty streak formation was carried out in fetal aortas from normocholesterolemic mothers (n = 22), hypercholesterolemic mothers (n = 33), and mothers who were hypercholesterolemic only during pregnancy (n = 27). Fetal plasma cholesterol levels showed a strong inverse correlation with fetal age (R = -0.88, P < 0.0001). In fetuses younger than 6 mo, fetal plasma cholesterol levels correlated with maternal ones (R = 0.86, P = 0.001), whereas in older fetuses no such correlation existed. Fetal aortas from hypercholesterolemic mothers and mothers with temporary hypercholesterolemia contained significantly more and larger lesions (758,651+/-87,449 and 451,255+/-37,448 micron2 per section, respectively; mean+/-SD) than aortas from normocholesterolemic mothers (61,862+/-9,555 micron2; P < 0.00005). Serial sections of the arch, thoracic, and abdominal aortas were immunostained for recognized markers of atherosclerosis: macrophages, apo B, and two different oxidation-specific epitopes (malondialdehyde- and 4-hydroxynonenal-lysine). Of the atherogenic sites that showed positive immunostaining for at least one of these markers, 58.6% were established lesions containing both macrophage/foam cells and oxidized LDL (OxLDL). 17.3% of all sites contained only native LDL, and 13.3% contained only OxLDL without monocyte/ macrophages. In contrast, only 4.3% of sites contained isolated monocytes in the absence of native or oxidized LDL. In addition, 6.3% of sites contained LDL and macrophages but few oxidation-specific epitopes. These results demonstrate that LDL oxidation and formation of fatty streaks occurs already during fetal development, and that both phenomena are greatly enhanced by maternal hypercholesterolemia. The fact that in very early lesions LDL and OxLDL are frequently found in the absence of monocyte/macrophages, whereas the opposite is rare, suggests that intimal LDL accumulation and oxidation contributes to monocyte recruitment in vivo.

Adult↗
PubMed1997

Occurrence of the same peroxidative compounds in low density lipoprotein and in atherosclerotic lesions from a homozygous familial hypercholesterolemic patient: a case report.

Oxidative modification of low density lipoprotein (LDL) and its byproducts may play a fundamental role in atherosclerosis. We report an in vitro analysis of LDL peroxidative compounds in an homozygous familial hypercholesterolemic (HFH) patient who subsequently died. During the autopsy, we analyzed lipids extracted directly from different atherosclerotic plaques, and we also provided an immunocytochemical analysis using the specific monoclonal antibody MDA2 (directed against malondialdeyde-lysine epitopes of oxidized LDL). The results showed that the same species of peroxidative compounds were present both in LDL in vitro and in lipids extracted directly from atherosclerotic lesions. Moreover, the immunocytochemistry analysis revealed a positive staining of atherosclerotic plaques, confirming the presence of LDL oxidation-specific epitopes. Although observation of a single case is necessarily limited, our findings are consistent with the hypothesis that oxidative modification of LDL is involved in human atherogenesis.

Adult↗
PubMed1997

Effects of melatonin in isolated rat papillary muscle.

Melatonin (N-acetyl-5-methoxytryptamine), the principal hormone of the vertebral pineal gland, elicits several neurobiological effects. However, the effects of melatonin on cardiac muscle are still unknown. The first goal of the study was to investigate the role of melatonin on myocardial contractility in isolated rat papillary muscle using dose-response curves to melatonin, to isoproterenol and calcium either in the presence or in the absence of melatonin (0.3 nM). Response curves to isoproterenol were additionally performed in the presence of melatonin plus the specific receptor antagonist N-acetyltryptamine (10 microM); the adenylate-cyclase stimulator forskolin (10 microM) was also used. Melatonin has no direct inotropic effect in isolated rat papillary muscle but counteracts isoproterenol but not [Ca2+] effects. In fact, the EC50 for isoproterenol was significantly higher in the presence than in the absence of melatonin (p < 0.001). This anti-adrenergic action occurs through an interaction to a specific cardiac receptor. Forskolin-stimulated adenylate cyclase induced an increase of contractile force (+118 +/- 25%) which was reduced in the presence of melatonin (+26 +/- 10%; p < 0.01). In conclusion, we found that melatonin possess anti-adrenergic effect in isolated rat papillary muscle. This phenomenon was abolished in the presence of its receptor antagonist N-acetyl-tryptamine demonstrating that melatonin operates through a specific cardiac receptor. The reduction of contractility increase, induced by forskolin-stimulated adenylate cyclase, shows that melatonin may act through a reduction of cyclic AMP accumulation.

Adenylyl Cyclases↗
PubMed1997

Effect of low density lipoprotein fatty acid composition on copper-induced peroxidation: 1H-nuclear magnetic resonance analysis.

Oxidation of low density lipoprotein (LDL) has been implicated in atherogenesis. An increased content of oleic acid in LDL and the substitution of monounsaturated for polyunsaturated fatty acids in the diet reduce LDL oxidation. With 1H-NMR analysis, all LDL modifications, including the production of copper-induced aldehyde products, can be evaluated simultaneously. The aim of the present study was to investigate whether the fatty acid composition of LDL affected the NMR evaluation of aldehyde compounds. The LDL of the samples utilized were rich in oleic fatty acid (26.9%). After 48 h of exposure to copper sulfate, the mean production of malonyldialdehyde (MDA) by LDL was 31.2 nmol/mg of protein. Moreover, in the present study NMR did not reveal large amounts of peroxidative compounds since the nanomolar amounts of MDA produced after exposure to copper sulfate could not be detected. This study also demonstrated that the fatty acid composition (i.e. the oleic:linoleic acid ratio) must be taken into account in the evaluation of LDL peroxidation by NMR. In particular, a high concentration of oleic acid may limit the formation of large amounts of peroxidative compounds generated after exposure to the oxidant copper sulfate.

Adult↗
PubMed1997

Glycosylation enhances oxygen radical-induced modifications and decreases acetylhydrolase activity of human low density lipoprotein.

BACKGROUND: Posttranslational nonenzymatic glycosylation of native low-density lipoprotein (n-LDL) occurs both in vitro and in vivo in diabetic patients. Glycosylated LDL (glc-LDL) behave similarly to oxidized LDL in some respects. In fact, unlike n-LDL, uptake the glc-LDL can occur in part by the "scavenger" receptor(s), as also demonstrated for oxidized LDL. The enzyme acetylhydrolase, carried by LDL, catabolizes platelet activating factor (PAF). This enzymatic activity is inhibited in oxidized LDL. However, it is unknown whether glc-LDL have reduced acetylhydrolase activity. OBJECTIVE: The first aim of the study was to investigate whether glc-LDL were more susceptible than n-LDL to oxidative modification, and which different oxygen radical species were involved in the phenomenon. Moreover, in order to investigate whether glycosylation may affect acetylhydrolase, we also measured this enzymatic activity in both n- and glc-LDL. METHODS: In vitro glc-LDL and n-LDL were exposed to the oxidants xanthine/xanthine oxidase (X/XO; 2 mM and 100 mU/ml, respectively), or CuSO4 (10 microM) for 18 hs at 37 degrees C. Parallel experiments were done in the presence of the superoxide radical scavenger superoxide dismutase (SOD; 330 U/ml), the hydrogen peroxide scavenger catalase (1000 U/ml), or the hydroxyl radical scavenger dimethylthiourea (10 mM) or dimethylsulfoxide (1 mM). Standards of PAF and lyso-PAF were visualized with iodine vapors after separation by thin layer chromatography. The distribution of label was determined by an imaging scanner. Labeled products were then isolated from the chromatography plate, and the amount of 3H-lyso-PAF formed was determined by liquid scintillation counting. RESULTS: Glc-LDL were more susceptible than n-LDL to lipid peroxidation (n-LDL 22.9 +/- 3.4 vs 34.8 +/- 4.2* nmoles/MDA/mg of protein in glc-LDL oxidized by X/XO and n-LDL 28.9 +/- 4.2 vs 40.4 +/- 4.1* in glc-LDL oxidized by CuSO4, *p < 0.05 vs n-LDL). SOD, but not other scavengers, prevented peroxidation, indicating an obligatory role for superoxide radicals. Oxidation of glc-LDL also induced a higher degree of apolipoprotein-B100 modifications than n-LDL, with increased electrophoresis mobility and decreased TNBS reactivity. These effects were similarly prevented by SOD. Finally, acetylhydrolase activity was significantly lower in glc-LDL than in n-LDL. CONCLUSION: Glycosylation increases LDL oxidation due to superoxide radicals, and also reduces acetylhydrolase activity. These phenomenona may contribute to enhance and/or accelerate the progression of atherosclerosis in diabetic patients.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1997

Decreased low-density lipoprotein oxidation after repeated selective apheresis in homozygous familial hypercholesterolemia.

Familial hypercholesterolemia was the first genetic disorder recognized to cause myocardial infarction. Patients with homozygous familial hypercholesterolemia have rapidly progressive coronary atherosclerosis with angina pectoris, myocardial infarction, or sudden death at a young age. Selective apheresis on dextran sulfate cellulose columns reduces mortality and may induce regression of coronary lesions. These patients have both increased levels and prolonged circulation residence time of low-density lipoprotein (LDL), which is not removed by cellular receptor. LDL oxidation may play a pivotal role in atherogenesis. LDL undergoes oxidation before being taken up by macrophages and then transformed into arterial wall foam cells. The aim of this study was to investigate LDL oxidation in eight homozygous patients with familial hypercholesterolemia during repeated LDL apheresis. LDL lipid peroxidation, estimated by conjugated-diene absorbance at 234 nm, lipid peroxides, and malondialdehyde showed an increased resistance against oxidation after repeated LDL apheresis. This phenomenon was also observed in the oxidative indexes of protein moiety of LDL (apolipoprotein-B100 fragmentation, trinitrobenzenesulfonic acid reactivity, and electrophoresis agarose mobility). Similarly, cholesteryl esterification was decreased after LDL apheresis. Thus selective LDL apheresis not only decreases the pool of LDL, but it also induces changes that render LDL less susceptible to oxidation. This phenomenon might contribute to reduce coronary atherosclerosis and thus mortality of these particular patients.

Apolipoprotein B-100↗
PubMed1997

Angina-induced protection against myocardial infarction in adult and elderly patients: a loss of preconditioning mechanism in the aging heart?

OBJECTIVES: The present study examined whether angina 48 h before myocardial infarction provides protection in adult and elderly patients. BACKGROUND: The mortality rate for coronary artery disease is greater in elderly than in young patients. In experimental studies, ischemic preconditioning affords an endogenous form of protection against ischemia-reperfusion injury in adult but not in senescent hearts. Angina before myocardial infarction, a clinical equivalent of experimental ischemic preconditioning, has a protective effect in adult patients. It is not known whether angina before myocardial infarction is also protective in aged patients. METHODS: We retrospectively verified whether antecedent angina within 48 h of myocardial infarction exerts a beneficial effect on in-hospital outcomes in adult (< 65 years old, n = 293) and elderly (> or = 65 years old, n = 210) patients. RESULTS: In-hospital death was more frequent in adult patients without than in those with previous angina (10% vs. 2.6%, p < 0.01), as were congestive heart failure or shock (10.7% vs. 3.3%, p < 0.02) and the combined end points (in-hospital death and congestive heart failure or shock) (20.7% vs. 5.9%, p < 0.0003). In contrast, the presence or absence of previous angina before acute myocardial infarction in elderly patients seems not to influence the incidence of in-hospital death (14.4% vs. 15.2%, p = 0.97), congestive heart failure or shock (11.0% vs. 11.9%, p = 0.99) and the combined end points (25.4% vs. 27.1%, p = 0.89). Logistic regression analysis models for in-hospital end points show that previous angina is a positive predictor in adult but not in elderly patients. CONCLUSIONS: The presence of angina before acute myocardial infarction seems to confer protection against in-hospital outcomes in adults; this effect seemed to be less obvious in elderly patients. This study suggests that the protection afforded by angina in adult patients may involve the occurrence of ischemic preconditioning, which seems to be lost in senescent patients.

Adult↗
PubMed1997

Reduced visual acuity in elderly people: the role of ergonomics and gerontechnology.

Gerontology is the scientific study of the ageing process and special problems of aged people. Ergonomics is an applied science for optimizing performance and productivity and reducing the risks of injury, discomfort and illness. Gerontechnology is concerned with fundamental and applied research on the complex interaction of elderly people with technological products and the built environment. It has the potential to improve the capability of people confronted by the challenges of ageing. We suggest that gerontechnology may have a particular role in relation to the reduction of visual acuity, and can improve the comfort and safety of older people.

Aged↗