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Biomedical subjects

L Mosca

Publications and source records attributed to L Mosca.

At least 19 recordsLinked to original sources
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

[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↗
PubMed1996

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↗
PubMed1996

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↗
PubMed1995

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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

Some biochemical properties of melanins from opioid peptides.

Opioid peptides are converted by mushroom tyrosinase into melanin-like compounds retaining the peptide moiety (opio-melanins). Opio-melanins, owing to the presence of the linked aminoacids and in contrast with DOPA-melanin, are soluble compounds. The enkephalin-generated melanins are cleaved by carboxypeptidase A and pronase whereas aminopeptidase M cannot remove aminoacids from the pigment. Enkephalins, as well as other opioid peptides, (alpha-endorphin, kyotorphin, esorphins) if oxidized in presence of DOPA and tyrosinase are readily incorporated into DOPA-melanin. The resulting mixed-melanins (opio-melanin + DOPA-melanin) can be solubilized in hydrophilic solvents. Melanin from leu-enkephalin exhibits paramagnetism as evidenced by an EPR spectrum identical to that of DOPA-melanin, but unlike the latter pigment, it does not appear to oxidize NADH, probably for the presence of the peptide moiety that exerts a hampering effect on the oxidizing capacity.

Amino Acid Sequence↗
PubMed1994

Early detection of abnormal coronary flow reserve in asymptomatic men at high risk for coronary artery disease using positron emission tomography.

BACKGROUND: The objective of this study was to compare coronary flow reserve (CFR) as a measure of vascular integrity in asymptomatic middle-aged men with family history of coronary artery disease (CAD) and a high-risk lipid profile with men without risk factors for CAD using positron emission tomography (PET). Previous studies suggested that the assessment of CFR is a sensitive means to detect vascular abnormalities before angiographic appearance of CAD. N-13 ammonia PET scanning allows noninvasive evaluation of regional and global myocardial blood flow and thereby quantification of CFR. METHODS AND RESULTS: We used dynamic N-13 ammonia PET imaging in conjunction with intravenous adenosine to assess regional and global CFR in asymptomatic middle-aged men with high risk (group 1, n = 16) and men without any known risk factors (group 2, n = 11) for CAD. Group 1 patients were selected based on positive family history of CAD, one or more lipid abnormalities, and a normal stress test. No patient had history of diabetes or hypertension. A three-compartment tracer kinetic model developed and validated in our institution was used to calculate myocardial blood flow. Absolute myocardial blood flow (mL/100 g per minute) was calculated in five territories for each patient. CFR was defined as the ratio of blood flow during maximum pharmacological vasodilatation to blood flow at rest. Comparisons of CFR between the two groups of patients were performed. The mean age was similar between groups (group 1, 49.3 +/- 0.5 years; group 2, 48.1 +/- 8.7 years; P = NS). Group 1 had higher total cholesterol (mg/dL) (241 +/- 43 versus 173 +/- 34, P < .001), total cholesterol to high-density lipoprotein cholesterol ratio (6.4 +/- 1.6 versus 4.1 +/- 1.4, P < .001), and low-density lipoprotein cholesterol (mg/dL) (167 +/- 33 versus 107 +/- 32). No group 1 patient had evidence of ischemia by exercise ECG or exercise of pharmacological radionuclide perfusion studies. The mean global absolute myocardial blood flow at rest was not significantly different among groups (group 1, 76 +/- 18; group 2, 66 +/- 8; P = NS; (in mL/100 g per minute). However, blood flow after adenosine infusion was higher for group 2 (group 1, 217 +/- 56; group 2, 264 +/- 39; P < .001), which resulted in a larger CFR for group 2 (group 1, 2.93 +/- 0.86; group 2, 4.27 +/- 0.52; P < .001). Univariate linear regression analysis revealed significant negative correlation of CFR to total cholesterol (P < .05, r = -.41), low-density lipoprotein (P < .05, r = -.38), and total cholesterol to high-density lipoprotein cholesterol ratio (P < .05, r = -.47). CONCLUSIONS: Noninvasive quantification of absolute myocardial blood flow by N-13 ammonia PET allows the detection of abnormal vasodilatory response to intravenous adenosine in male patients with family history of CAD and high-risk lipid profiles. Early assessment of alterations of vascular reactivity to adenosine in relation to high-risk lipid profiles in asymptomatic men may allow early detection of preclinical atherosclerosis and may initiate modification and/or elimination of risk factors that may slow, retard, or even reverse the progression of CAD.

Adenosine↗
PubMed1992

Melanins production from enkephalins by tyrosinase.

Leu-enkephalin and Met-enkephalin are oxidized in vitro by mushroom and sepia tyrosinase giving rise to synthetic melanins whose production is dependent on incubation time and on enzyme concentration. The Enk-melanins formed are acid-insoluble brownish or reddish pigments showing a continuous absorbance in the visible region when dissolved in basic solution. The presence of the amino acid chain makes them fully soluble in pH 7.4 0.05 M phosphate buffer and methanol.

Amino Acids↗
PubMed1992

Hypophyseal pathology in AIDS.

One hundred and eleven pituitary glands of patients (93 males, 18 females; mean age 32 years, 5 months) who died of fully developed AIDS or ARC were examined under light microscopy with the aid of immunohistochemistry. On post mortem (p.m.) examination a wide series of multiorgan alterations was noticed. Microscopically various lesions in both adeno- and neurohypophysis were seen. These ranged from vessel damage to secondaries to systemic infections, neoplasms and functional derangements. Necrotic lumps due to recent infarction could appear in both parts of the gland, while old fibrous scars sustained a previously overcome necrosis. Different pathogens (mainly fungi) could be seen either within the gland or arising from its meningeal surroundings. Examples of tumour pathology were provided by microadenomas, gliosis/gliomas; the frequency of adenomas (11.7%) was similar to that typical of senility. The functional impairment was mainly connected with ACTH cell hyperplasia, which seems in keeping with corticoadrenal or ACTH-receptor damage.

AIDS-Related Complex↗
PubMed1990

Bronchial carcinoids with S-100 positive sustentacular cells. A comparative study with gastrointestinal carcinoids, pheochromocytomas and paragangliomas.

Fourty-six bronchial carcinoids, twelve tumourlets and twenty areas of neuroendocrine cell dysplasia (NED) were immunohistochemically evaluated for various neuroendocrine markers, S-100 protein (S-100), myelin basic protein, intermediate filaments, actin, Leu-7 and several neurohormonal polypeptides. Eighteen of the bronchial carcinoids (39.1%) showed a biphasic cell pattern, with abundant stellate-shaped S-100 positive cells (SC). SC were not reactive for chromogranin A, myelin basic protein, cytokeratins, neurofilaments, glial fibrillary acidic protein or actin, and were only occasionally weakly positive for vimentin. SC were not detected in the tumourlets nor in the NED observed. For comparison a group of other neuroendocrine tumours (11 gastrointestinal carcinoids, 4 pheochromocytomas and 4 paragangliomas) were immunostained for S-100, chromogranin A and actin. SC similar to the ones detected in the bronchial carcinoids could be detected in appendiceal carcinoids, paragangliomas and in two out of four pheochromocytomas. Our present data are in keeping with a Schwannian/sustentacular nature of SC rather than that of a histiocytic or myoepithelial nature. We suggest that SC-rich bronchial carcinoids are biphasic tumours, which could be designed "paraganglioid" bronchial carcinoids. The relationship between SC-rich bronchial carcinoids and tumourlets/NED is a matter of further investigation: SC-rich bronchial carcinoids may either differentiate in a biphasic pattern during tumoural growth or may not be histogenetically related to tumourlets.

Adrenal Gland Neoplasms↗
PubMed1989

Large cell neuroendocrine carcinoma of the lung.

Large cell neuroendocrine (LCNE) carcinomas of the lung are a newly recognized, highly aggressive and frequently misdiagnosed entity. We report a case of stage I LCNE lung carcinoma initially misdiagnosed as large cell undifferentiated carcinoma or poorly differentiated adenocarcinoma. The tumor was very extensively necrotic and its neuroendocrine differentiation was only demonstrable with immunohistochemical staining with PHE-5 monoclonal antibody and with antisera against synaptophysin and calcitonin. ACTH, somatostatin and neurofilaments were not demonstrable. The clinical course was ominous and the patient died within 17 months. The reason for this rapid fatal outcome could be ascribed either to the neuroendocrine phenotype of the tumor, or to the extensive necrosis, or both.

Adenocarcinoma↗