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Biomedical subjects

L Mosca

Publications and source records attributed to L Mosca.

At least 55 records · Page 3Linked to original sources

Melanins from tetrahydroisoquinolines: spectroscopic characteristics, scavenging activity and redox transfer properties.

Tetrahydroisoquinolines (TIQs) are endogenous compounds deriving from the nonenzymatic Pictet-Spengler condensation of catecholamines (CA) with aldehydes. TIQs have been extensively studied in the last years not only because they have been found in the brain of postmortem specimens of Parkinson's patients, but also because they are able to induce parkinsonian symptoms if injected in animals. In the present article we demonstrate that TIQs bearing a catecholic moiety (tetrahydropapaveroline, salsolinol, laudanosoline, and apomorphine) are easily oxidized in the presence of hydrogen peroxide by various enzymes--i.e., peroxidase (POD), lipoxygenase (LOX), and xanthine oxidase (XO)--into the corresponding TIQ-melanins. The kinetic parameters of the above-mentioned reactions and some spectroscopic characteristics of the synthetized pigments are reported. In particular, UV-VIS and EPR spectra emerge as very similar to those exhibited by dopa-melanin. Furthermore, TIQ-melanins appear to be similar to dopa-melanin regarding some specific physico-chemical properties: NADH-oxidizing properties, oxy-radicals scavenging activity, and ability to form soluble mixed polymers with melanins from opioid peptides.

Electron Spin Resonance Spectroscopy↗

Production of melanin pigments by cytochrome c/H2O2 system.

In the presence of hydrogen peroxide cytochrome c can perform the oxidation of catecholamines and their S-cysteinyl-derivatives yielding melanins as final products. The initial reaction rate is linearly dependent on cytochrome c and H2O2 concentration; the reaction follows the Michaelis and Menten kinetics both for H2O2 and hydrogen donors. Sulfhydryl compounds inhibit the formation of the pigment. The reported data indicate that a heme-containing protein belonging to the mitochondrial chain can accelerate the oxidation of catecholamines to eumelanins.

Animals↗

Gender differences in barriers to lifestyle change for cardiovascular disease prevention.

Achieving and maintaining a healthy lifestyle are important aspects of a cardiovascular disease prevention program. Few data have evaluated barriers to lifestyle change by gender. We studied self-reported barriers to lifestyle change and evaluated support systems to make positive changes in 293 patients (186 men, 107 women) enrolled in a multidisciplinary preventive cardiology clinic. Subjects were asked to rate barriers and support systems on a scale of 1 to 5, with 1 being very important and 5 not important. Women ranked self-esteem as the most important barrier and rated it significantly higher than did men (p = 0.0003). Women also rated money, knowledge, skills, and stress significantly higher than did men (p < 0.05). Physicians were rated as the most important source of support for both genders. Women, compared with men, rated dietitians, exercise physiologists, nurses, counselors, family members, and social/religious groups as more important sources of support. These data suggest that gender differences exist in barriers to lifestyle change. Psychosocial factors should be considered important elements of programs designed to help patients make positive lifestyle changes.

Adult↗

Hormone and nonhormone therapy for the maintenance of postmenopausal health: the need for randomized controlled trials of estrogen and raloxifene.

Multiple health benefits have been postulated for the long-term use of hormone therapy in postmenopausal women, most notably for prevention of osteoporotic fractures and coronary heart disease, as well as several risks, including cancer of the breast and uterus and venous thromboembolism. Cardiovascular disease is the most common cause of death among postmenopausal women. If real, the reduction in risk of coronary heart disease by hormone use suggested by observational studies would likely outweigh the risks. The decision to initiate and maintain hormone therapy is complicated by uncertainties about estrogen's true benefits and risks. Raloxifene, a selective estrogen receptor modulator (SERM), appears to have many of the benefits of estrogen without the cancer risks. It is not known if SERMs can provide significant cardiovascular protection. This article reviews the relation of use of postmenopausal hormones and raloxifene to women's health and addresses the need for large randomized trials to quantify the effect of both postmenopausal estrogen and raloxifene on cardiovascular health.

Cardiovascular Diseases↗

Greater dietary intake of simple carbohydrate is associated with lower concentrations of high-density-lipoprotein cholesterol in hypercholesterolemic children.

Hypercholesterolemic children are increasingly being treated with lipid-lowering diets, but little research has focused on the effects of specific dietary substitutions on HDL cholesterol. We examined the relation between carbohydrate intake and HDL cholesterol in hypercholesterolemic children consuming fat-restricted diets. We obtained 3-d food records for 67 children (mean age: 5.8 +/- 2.5 y) referred for the treatment of hypercholesterolemia. Mean plasma HDL cholesterol was 1.12 +/- 0.21 mmol/L and total cholesterol was 5.99 +/- 1.39 mmol/L. Dietary intake comprised (percentage of total energy) 24.9 +/- 5.1% fat, 59.9 +/- 6.5% carbohydrate, and 16.5 +/- 3.4% protein. Carbohydrate intake included 30.7 +/- 7.4% from simple and 22.6 +/- 6.2% from complex carbohydrates. HDL cholesterol was positively correlated with intake of total fat (r = 0.44, P < 0.001) and saturated fatty acids (r = 0.43, P < 0.001) and inversely correlated with intake of total carbohydrate (r = -0.55, P < 0.001) and simple carbohydrate (r = -0.40, P < 0.001), but not with complex carbohydrate (r = -0.02). The significant inverse relation between simple carbohydrate intake and HDL cholesterol remained after intakes of saturated, monounsaturated, and polyunsaturated fatty acids; intake of complex carbohydrates; dietary cholesterol; plasma triacylglycerol; and age were adjusted for with multivariate techniques. In summary, higher dietary intake of simple carbohydrates was associated with lower HDL-cholesterol concentrations in hypercholesterolemic children consuming reduced-fat diets.

Body Mass Index↗

Preoperative smoking habits and postoperative pulmonary complications.

OBJECTIVE: To examine the effect of preoperative smoking behavior on postoperative pulmonary complications. DESIGN: Prospective cohort study. SETTING: The Veterans Administration Medical Center, Syracuse, NY. PARTICIPANTS: Patients scheduled for noncardiac elective surgery (n=410). MEASUREMENTS AND RESULTS: Smoking status was determined by self-report. Postoperative pulmonary complications were determined by systematic extraction of medical record data. Postoperative pulmonary complications occurred in 31 of 141 (22.0%) current smokers, 24 of 187 (12.8%) past smokers, and 4 of 82 (4.9%) never smokers. The odds ratio (OR) for developing a postoperative pulmonary complication for current smokers vs never smokers was 5.5 (95% confidence interval [CI], 1.9 to 16.2) and 4.2 (95% CI, 1.2 to 14.8) after adjustment for type of surgery, type of anesthesia, abnormal chest radiograph, chronic cough, history of pulmonary disease, history of cardiac disease, history of COPD, education level, pulmonary function, body mass index, and age. Current smokers who reported reducing cigarette consumption prior to surgery were more likely to develop a complication compared with those who did not (adjusted OR=6.7, 95% CI, 2.6 to 17.1). CONCLUSIONS: Current smoking was associated with a nearly sixfold increase in risk for a postoperative pulmonary complication. Reduction in smoking within 1 month of surgery was not associated with a decreased risk of postoperative pulmonary complications.

Confidence Intervals↗

Clinical predictors of oxidized low-density lipoprotein in patients with coronary artery disease.

Oxidized low-density lipoprotein (LDL) may play a key role in the initiation and progression of atherosclerosis. Risk factors for elevated levels of oxidized LDL are not well established and may be important in identifying individuals who may benefit from antioxidant supplementation or interventions to reduce oxidant stress. The purpose of this study was to determine if clinical parameters predict levels of oxidized LDL. We evaluated the relation between clinical parameters and oxidized LDL in 45 nonsmoking, nondiabetic patients (39 men and 6 women) with coronary artery disease. Oxidized LDL was assessed by measurement of conjugated dienes, lipid peroxides, and thiobarbituric reactive substances (TBARS) at 0 hours to evaluate baseline oxidant stress and postincubation with an oxidizing agent to assess the capacity of LDL for peroxidation. Results were lipid standardized and were not materially altered by multivariate adjustment. Significant predictors of increased oxidized LDL included female sex, family history of premature cardiovascular disease, increased percent body fat, increased body mass index, increased heart rate at rest, history of smoking, exercise <4 times per week, and no regular wine consumption. These data suggest that clinical parameters correlate with levels of oxidized LDL and may be useful in identifying patients at risk for increased oxidant stress.

Adult↗

Antioxidant nutrient supplementation reduces the susceptibility of low density lipoprotein to oxidation in patients with coronary artery disease.

OBJECTIVE: This study sought to determine the effect of antioxidant supplementation on the susceptibility of low density lipoprotein (LDL) to oxidation in patients with established cardiovascular disease (CVD). BACKGROUND: Data are inconsistent regarding the role of antioxidant nutrients in the prevention of CVD. METHODS: The study design was a 12-week, double-blind, placebo-controlled clinical trial. Patients with CVD (n = 45) were randomized to 1) placebo control; 2) 400 IU of vitamin E, 500 mg of vitamin C, 12 mg of beta-carotene (mid-dose); or 3) 800 IU of vitamin E, 1,000 mg of vitamin C, 24 mg of beta-carotene (high dose) daily. Reduced susceptibility of LDL to oxidation was estimated by an increase in lag phase (minutes). Baseline and 6- and 12-week measurements of lipoproteins and lag phase were obtained. Plasma levels of antioxidants were measured at baseline and 12 weeks. RESULTS: Concentrations of alpha-tocopherol, vitamin C and beta-carotene significantly increased in the mid- and high dose groups during the trial. Lag phase significantly increased from baseline (190.1 +/- 63.8 min [mean +/- SD]) to 12 weeks (391.1 +/- 153.0 min) in the high dose group (p < 0.01). A nonsignificant increase in lag phase in the mid-dose group was observed during the same time interval. A dose response was found for mean percent change from baseline to 12 weeks for lag phase for the placebo, mid- and high dose groups (p = 0.004 for trend). CONCLUSIONS: A high dose combination of antioxidant nutrients reduces the susceptibility of LDL to oxidation in patients with CVD and may be useful in secondary prevention.

Adult↗

A specific assay for discriminating between peroxidase and lipoxygenase activities.

Peroxidases are widespread heme-containing enzymes able to catalyze the oxidation of a large array of organic substrates. There is growing interest in the measurements of peroxidase activity. We noticed that many substrates used in the routine assays for the biological and cytological determinations of peroxidase could be oxidized by lipoxygenase. We found interesting to set up a procedure to detect selectively peroxidase. In the present note, we report a fluorometric test for peroxidase detection using phenolic compounds or hydroxycoumarins.

Amino Acid Sequence↗

[New possible pathways for melanogenesis: opiomelanins].

Opioid peptides and other Tyr-NH2-terminal peptides are substrates in vitro for mushroom and sepia tyrosinase giving rise to synthetic melanins retaining the peptide moiety (opiomelanins). The melanopeptides are characterized by a total solubility in hydrophilic solvents at neutral and basic pH. Opioid peptides (enkephalins, endorphins, esorphins), if oxidized by tyrosinase in the presence of Dopa are easily incorporated into Dopa-melanin, producing mixed-type pigments which can also be solubilized in hydrophilic solvents. Melanins deriving from opioid peptides exhibit paramagnetism as evidenced by an EPR spectrum identical to that of Dopa-melanin. However the presence of the linked peptide chain is able to influence dramatically the electron transfer properties and the oxidizing behaviour of the melanopeptides, so that whereas Tyr-Gly-melanin appears to behave as Dopa-melanin, Enk-melanin does not exhibit any oxidizing activity. Opiomelanins are characterized by a peculiar UV-VIS spectrum i.e. by the presence of a well distinct peak (330 nm) disappearing upon chemical treatment by acid hydrolysis. Opiomelanins are stable pigments at neutral and basic pH in the dark, whereas H2O2 addition leads to a 15% degradation. Under simulated solar illumination opiomelanins are more easily destroyed with respect to Dopa-melanin with increasing degradation of exposed to increased hydrogen peroxide concentrations and more alkaline pH. Some speculations on the possible existence and role of opiomelanins have been outlined.

Culture Media↗

Leisure and occupational physical activity and risk of colorectal adenomatous polyps.

Multiple studies have shown a protective effect for physical activity on the incidence of colorectal cancer, but few have addressed its association with incident adenomas and none have investigated its association with metachronous adenomas. We interviewed 2,001 patients undergoing colonoscopy in 3 New York City practices between 1986-1988. Of these, 298 had a first diagnosis of adenomas, 506 had normal colonoscopies, 197 had metachronous adenomas and 345 had normal colonoscopies with a past history of adenomas. Subjects were queried regarding use of moderate amounts of recreational exercise (swimming, jogging, biking, racket sports and other sports) on a regular basis, and were also asked to estimate their level of physical activity. Occupational physical activity was assessed through a blinded coding of occupational titles. After adjusting for age, years of education, body mass index, total caloric intake, dietary fiber intake, dietary fat intake and years of cigarette smoking, protective effects of borderline significance were observed among males for leisure physical activity for metachronous and incident cases. Occupational physical activity was found to be significantly protective in male incident cases. Men with increased levels of either occupational or leisure activity showed a reduction for incident and metachronous cases. No effects were observed for females. Thus, in this study, both leisure and occupational physical activity were associated with a reduced risk of incident and metachronous adenomas among men but not women.

Adenoma↗

Pheomelanin production by the lipoxygenase-catalyzed oxidation of 5-S-cysteinyldopa and 5-S-cysteinyldopamine.

5-S-cysteinyl-dopa (cysdopa) and 5-S-cysteinyl-dopamine (cysdopamine) are oxidized in vitro by soybean lipoxygenase (LOX) in the presence of hydrogen peroxide giving rise to the corresponding pheomelanins. The reaction is activated by caffeic acid and other catechols, suggesting a cofactor role for these compounds. The activating effect is proportional to the concentration of the cofactor, with a saturation profile. The activation extent of the various cofactors is directly related to LOX affinity for the same compounds. The possible implications of the peroxidative action of LOX in Parkinson's disease and in aging are discussed.

Catechols↗

Spectroscopic features of native and bleached opio-melanins.

Opioid peptides can be converted by tyrosinase into melanin-like compounds, in which the peptide moiety is retained. Such pigments, named opio-melanins, exhibit a characteristic absorption spectrum with a maximum at about 330 nm and a different solubility behaviour with respect to dopa-melanin, being completely soluble in hydrophylic solvents at neutral and basic pH. Opio-melanins precipitate in aqueous solutions below pH 5.0, and show apparent pKa values of 3.1, 3.6 and 4.4 for Tyr-Gly-melanin, Tyr-Gly-Gly-melanin and leuenk-melanin, respectively. The concomitant oxidation of dopa and opioid peptides by tyrosinase produces mixed polymers, showing the distinctive absorption peak at 330 nm. In the dark, in the pH range 5.5-7.0 the pigments are completely stable, whereas H2O2 addition provokes a slight degradation. At higher pH values or under simulated solar illumination with or without hydrogen peroxide, bleaching occurs more rapidly than in dopa-melanin. Upon photoirradiation the absorption spectrum of opio-melanins undergoes a marked variation, the peak at 330 nm being replaced by a broad shoulder in the range 280-350 nm. The absorption spectra of native and bleached pigments and the extent of opio-melanins degradation by bleaching agents, confirm the hypothesis that the different initial structure of the precursors accounts for a final diverse polymeric architecture of these pigments with respect to dopa-melanin.

Amino Acid Sequence↗

Production of melanin pigments by chemical and enzymatic oxidation of tetrahydroisoquinolines.

Tetrahydropapaveroline (THP) oxidation was studied in various experimental conditions by absorbance spectroscopy. THP was found to be easily oxidized by mushroom tyrosinase, giving rise to the formation of a chromophore (THP-chrome) with absorption maxima at 308 and 470 nm. The oxidation further proceeds leading to the formation of a melanin-like pigment. The use of periodate as oxidant at pH 7.4 allows the visualization of the THP-chrome, as well. Other tetrahydroisoquinolines bearing a catechol moiety, such as salsolinol, laudanosoline and apomorphine, have been found to be easily oxidized in the same conditions, giving rise to pigmented derivatives. The products of THP oxidation are able to copolymerize with dopa or opioid peptides in the presence of tyrosinase, generating mixed-type melanins.

Amino Acid Sequence↗

Lipoxygenase-catalyzed oxidation of catecholamines.

Dopa and structurally related catecholamines in presence of hydrogen peroxide are oxidized in vitro by soybean lipoxygenase producing the corresponding melanin pigments. The kinetic parameters of the catecholasic reaction, measured as aminochrome formation, have been calculated. The rate of peroxidation depends on catecholamine and hydrogen peroxide concentration. The optimum pH for the peroxidative activity of the enzyme is around 8.5. The enzyme, at higher pH values (pH 9-9.5), is also able to perform an oxidative reaction of the substrates. Implications of the possible biochemical relevance of the reactions are discussed.

Adrenochrome↗