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C De Luca

Publications and source records attributed to C De Luca.

At least 19 recordsLinked to original sources
PubMed2006

Mutations in yeast mt tRNAs: specific and general suppression by nuclear encoded tRNA interactors.

Mutations in mitochondrial tRNA genes can produce alterations in tRNA structure resulting in defective mitochondrial protein synthesis and hence respiratory defects. Such defects are often at the origin of neurodegenerative diseases in humans and can be easily studied in yeast since respiratory deficient mutants are viable. Several nuclear encoded tRNA interactors have been shown to rescue the mitochondrial defects due to mutations in mitochondrial tRNAs. Among these, we have identified the gene for the mitochondrial protein synthesis elongation factor EF-Tu and the specific mt aminoacyl-tRNA synthetases. We also observed that the respiratory defects and the effect of the TUF1 over-expression were strongly strain dependent. The importance of the nuclear background in which the mitochondrial mutation is expressed was investigated by changing the nuclear context. Finally, we demonstrated, using the RT-PCR method, the existence of significantly variable levels of the TUF1 transcript among strains with functional and dysfunctional mitochondria.

Amino Acyl-tRNA Synthetases↗
PubMed2003

The yeast counterparts of human 'MELAS' mutations cause mitochondrial dysfunction that can be rescued by overexpression of the mitochondrial translation factor EF-Tu.

We have taken advantage of the similarity between human and yeast (Saccharomyces cerevisiae) mitochondrial tRNA(Leu)(UUR), and of the possibility of transforming yeast mitochondria, to construct yeast mitochondrial mutations in the gene encoding tRNA(Leu)(UUR) equivalent to the human A3243G, C3256T and T3291C mutations that have been found in patients with the neurodegenerative disease MELAS (for mitochondrial 'myopathy, encephalopathy, lactic acidosis and stroke-like episodes'). The resulting yeast cells (bearing the equivalent mutations A14G, C26T and T69C) were defective for growth on respiratory substrates, exhibited an abnormal mitochondrial morphology, and accumulated mitochondrial DNA deletions at a very high rate, a trait characteristic of severe mitochondrial defects in protein synthesis. This effect was specific at least in the pathogenic mutation T69C, because when we introduced A or G instead of C, the respiratory defect was absent or very mild. All defective phenotypes returned to normal when the mutant cells were transformed by multicopy plasmids carrying the gene encoding the mitochondrial elongation factor EF-Tu. The ability to create and analyse such mutated strains and to select correcting genes should make yeast a good model for the study of tRNAs and their interacting partners and a practical tool for the study of pathological mutations and of tRNA sequence polymorphisms.

Amino Acid Substitution↗
PubMed2001

Novel hypotensive agents from Verbesina caracasana. 8. Synthesis and pharmacology of (3,4-dimethoxycinnamoyl)-N(1)-agmatine and synthetic analogues.

The more polar metabolites from the Venezuelan plant Verbesina caracasana, i.e., N(3)-prenylagmatine, (3,4-dimethoxycinnamoyl)-N(1)-agmatine, agmatine, and galegine (prenylguanidine), previously reported (Delle Monache, G.; et al. BioMed. Chem. Lett. 1999, 9, 3249-3254), have been synthesized following a biosynthetic strategy. The pharmacologic profiles of various synthetic analogues of (3,4-dimethoxycinnamoyl)-N(1)-agmatine (G5) were also analyzed, to shed some light on the structure-activity relationship of these compounds. Derivatives with the (E)-configuration and/or with a p-methoxybenzoyl moiety were found to be responsible for higher hypotensive effects, which were associated with a slight and, in some cases, not dose-related increase of cardiac inotropism, with variable and not significant chronotopic responses, and, only at higher doses, with effects of respiratory depression. Either an increase (to six) or a decrease (to two) of the number of methylene groups in the alkyl chain of (E)-G5 did not change blood pressure responses, while slightly increasing the positive inotropic ones. At pharmacological doses, all the studied compounds showed hypotensive and slight positive inotropic effects without relevant chronotropic and respiratory actions.

Agmatine↗
PubMed2001

Effects of cyclic adenosine-monophosphate on growth and PSA secretion of human prostate cancer cell line.

Prolonged increase of cyclic adenosine-monophosphate (cAMP) level in the culture medium of a well differentiated human prostatic cancer cell (LNCaP) inhibits cellular growth and stimulates PSA secretion. The differentiation of the cells tested was documented by their responsiveness to androgens and the ability to synthesize cellular markers of differentiation (PSA). The raise in cAMP level was produced by dibutyryl cyclic AMP (DBcAMP) or by agents acting at distinct levels in the pathway of cAMP generation (forskolin) or degradation (IBMX). Each of these three agents in a range of concentrations between 10-4-10-6 M had an inhibitory effect on the growth which is dose and time-dependent. The inhibition was reversible as demonstrated by complete restoration of cell growth soon after the withdrawal of the substances from the culture medium. When cAMP levels in culture medium was raised, an increase in PSA content was observed. However, the effects of cAMP on PSA content was not due to increase in PSA synthesis, since simultaneous measurement of secreted and cellular PSA indicated that the principal effect of the cyclic nucleotide was to enhance the secretion of stored PSA. Furthermore the inhibition of cellular growth by cAMP suggests new approaches in prostatic carcinoma therapy.

1-Methyl-3-isobutylxanthine↗
PubMed2000

Th2 cell membrane factors in association with IL-4 enhance matrix metalloproteinase-1 (MMP-1) while decreasing MMP-9 production by granulocyte-macrophage colony-stimulating factor-differentiated human monocytes.

Monocytes/macrophages are directly involved in tissue remodeling and tissue destruction through the release of matrix metalloproteinases (MMP). In the present study, we examined the effect mediated by contact of polarized Th cells with mononuclear phagocytes on the production of MMP-1, MMP-9, and their inhibitor. Plasma cell membranes from Ag-activated Th1 and Th2 cells were potent inducers of MMP-1 production by THP-1 cells. Cell membrane-associated TNF was found to be only partially involved in MMP-1 induction by both Th1 and Th2 cells. In Th2 cells exclusively, membrane-associated IL-4 induced MMP-1 production by THP-1 cells. This membrane-associated IL-4 effect was additive to that of TNF and was specifically observed on MMP-1 as MMP-9 production was concomitantly inhibited. Similarly, soluble IL-4 induced THP-1 cells to produce MMP-1, its effect proving additive to that of soluble TNF and to that of cell membranes of mitogen-activated HUT-78 cells. Its activity was blocked by IL-4 neutralization, and was unaffected by the presence of indomethacin. These effects on THP-1 cells were observed at protein and mRNA levels. Although inhibitory on freshly isolated peripheral blood monocytes, soluble IL-4 enhanced T cell-induced MMP-1 and inhibited MMP-9 production both at protein and mRNA levels in monocytes cultured for 7 days in the presence of GM-CSF. Thus, in contrast with previously reported effects, Th2 and IL-4 specifically induce MMP-1 production by mononuclear phagocytes at various stages of differentiation. This IL-4 activity may be relevant to pathological conditions dominated by Th2 inflammatory responses, resulting in tissue remodeling and destruction.

Adjuvants, Immunologic↗
PubMed1999

Further hypotensive metabolites from Verbesina caracasana.

After the isolation of caracasanamide and caracasandiamide, further hypotensive components of Verbesina caracasana were shown to be N3-prenylagmatine, N1-3',4'-dimethoxycinnamoylagmatine, agmatine and galegin (prenylguanidine). The structures were assigned on the basis of the spectral data of both metabolites and products from their alkaline hydrolyses. A pharmacological analysis of these products is also presented.

Animals↗
PubMed1999

Novel hypotensive agents from Verbesina caracasana. 6. Synthesis and pharmacology of caracasandiamide.

Caracasandiamide, a second hypotensive agent isolated from Verbesina caracasana, is the cyclobutane dimer (truxinic type) of the previously reported 1-[(3, 4-dimethoxycinnamoyl)amino]-4-[(3-methyl-2-butenyl)guanidino]butane (caracasanamide) (Delle Monache, G.; et al. BioMed. Chem. Lett. 1992, 25, 415-418). The structure was confirmed by synthesis starting from beta-truxinic acid obtained by photoaddition of 3, 4-dimethoxycinnamic acid. The dimer was coupled with 2 mol of prenylagmatine to give caracasandiamide in satisfactory yield. By contrast, the direct photodimerization of caracasanamide was unsuccessful. Caracasandiamide, assayed by the iv route in anesthetized rats at doses ranging from 50 to 3200 microgram/kg of body weight, was found to have no appreciable effect on heart rate. At lower doses, the drug stimulates breathing and increases cardiac inotropism, stroke volume, and cardiac output, thus augmenting blood pressure and aortic flow. At higher doses, caracasandiamide depresses breathing likely through central neurogenic mechanisms (not involved in the cardiovascular effects), continues to stimulate cardiac inotropism, and induces, by reducing peripheral vascular resistance, arterial hypotension with reduction of both aortic flow and stroke volume. These cardiovascular effects appear to involve complex interactions at the level of the peripheral beta(1)-, beta(2)-, and alpha(2)-adrenoreceptor-dependent as well as M(2)- and M(4)-cholinergic receptor-dependent transductional pathways both in cardiovascular myocells and at the level of the postganglionic sympathetic endings (with reserpine- and guanethidine-like mechanisms). The cardiovascular effects of caracasandiamide, different from those of caracasanamide, do not depend on significant actions on the central nervous system and on baroreflex pathways. In a similar manner and more effective than caracasanamide, caracasandiamide may be considered a hypotensive and antihypertensive drug. It is devoid of some of the negative side effects, e.g., reflex tachycardia and decreased cardiac inotropism, which are shown by the majority of the most common antihypertensive and vasodilator drugs.

Animals↗
PubMed1999

Multiple light-harvesting II polypeptides from maize mesophyll chloroplasts are distinct gene products.

The major light-harvesting complex of photosystem II in higher plants is known as LHCII. It is composed of a number of chlorophyll-binding proteins sharing epitopes with each other. The number of apoproteins resolved by fully denaturing sodium dodecylsulfate polyacrylamide gel electrophoresis varies in different species. In order to know if this heterogeneity is caused by the expression of a number of homologous genes or if it is the product of post-translational modifications, we have resolved the six major apoproteins of Zea mays LHCII. Each protein is purified to homogeneity, subjected to direct protein sequencing and the sequences compared with those deduced from lhcb genes in maize and other organisms. All of the six proteins are distinct gene products, since they show differences in their primary structure. Three apoproteins are identified as products of type I lhcb genes and one each as type II and type III gene products. A sixth protein does not fit the requirements for any of the lhcb genes so far cloned and is therefore probably the product of an lhcb gene type not yet described. Our results clearly show that the major source of LHCII protein heterogeneity is the expression of many lhcb genes. Fractionation of maize LHCII by non-denaturing flat-bed isoelectric focusing resolves at least five major isoforms showing distinct differences in their polypeptide composition and also differing in their spectroscopic properties, thus suggesting that individual Lhcb gene products have distinct pigment-binding properties.

Amino Acid Sequence↗
PubMed1999

Blood antioxidant status and urinary levels of catecholamine metabolites in beta-thalassemia.

It has been reported that iron overload in beta-thalassemia leads to an enhanced generation of reactive oxygen species and to oxidative stress. We have studied the oxidant/antioxidant imbalance in the blood of 48 transfusion-dependent beta-thalassemic patients (TLP) (17 males, 31 females, 11-22 year), under chelation therapy, and in 40 sex and age matched healthy controls (CTR). Plasma and lymphocyte levels of vitamin E (Vit E), ubiquinol (CoQ10H2), ubiquinone (CoQ10), plasma concentrations of vitamin A (Vit A), beta-carotene, lycopene, vitamin C (Vit C), total thiols, fatty acid patterns of phospholipids (PL-FA), and plasma and urinary markers of lipoperoxidation (TBA-RM, conjugated dienes, and azelaic acid (AZA), as well as the urinary levels of catecholamine and serotonin metabolites, were evaluated by gas chromatography-mass spectrometry (GC-MS), HPLC and spectrophotometry. Routine laboratory blood analyses were performed on the same samples; 39/48 TLP were HCV positive. Blood samples were collected just before transfusion, the 24 h urine samples the day before. Our results clearly showed that a severe oxidative stress occurs in the plasma of TLP in comparison with CTR. In fact, the levels of lipophilic antioxidants and ascorbate were severely depleted: CoQ10H2 (-62.5%), total CoQ10 (-35.1%), Vit E (-43.8%), beta-carotene (-31.1%), lycopene (-63.7%), Vit A (-35.9%), Vit C (-23.1%). The impairment of the antioxidant status was associated with elevated plasma levels of by-products of lipoperoxidation and urinary concentrations of catecholamine metabolites and of AZA, indicating a high degree of both neurological stress and lipoperoxidation. A significant positive correlation was found between vitamin E and non-transferrin-bound iron (NTBI) (r = -0.81; p < 0.001), while no correlation was found between antioxidant depletion and ferritin serum levels, average blood consumption, or the presence of clinical complications. The administration of selective antioxidants along with an appropriate diet might represent a promising way of counteracting oxidative damage and its deleterious effects on the progression of the disease.

Adolescent↗
PubMed1998

Epidermal oxidative stress in vitiligo.

Epidermal levels of enzymatic and non-enzymatic antioxidants such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), vitamin E (Vit E), ubiquinol (CoQ10H2), and reduced glutathione (GSH), as well as polyunsaturated fatty acids of phospholipids (PL-PUFA), were evaluated in the affected epidermis of 15 patients with active vitiligo (AVP) and in the corresponding epidermis of 15 healthy phototype matched controls. The epidermal levels of CoQ10H2, Vit E, GSH, and CAT activity were significantly reduced in AVP and were associated with a marked increase of oxidized glutathione, whereas SODs and GSH-Px activities and ubiquinone concentration remained similar to control values. Antioxidant deficiency, in particular the decline of lipophilic antioxidants, i.e., CoQ10H2 and Vit E, accounts well for PL-PUFA reduction observed in vitiligo epidermis, mainly affecting C18:3 n-3, C20:3 n-6, C20:4 n-6, and C22:6 n-3 fatty acids and suggesting the occurrence of a lipoperoxidative process. In conclusion, both an imbalance of the intracellular redox status and a significant depletion of enzymatic and non-enzymatic antioxidants feature the epidermis of AVP, and represent a fingerprint of an abnormal oxidative stress leading to epidermal cell injury.

Adult↗
PubMed1997

Gallstones and diabetes: a case-control study in a free-living population sample.

Data on the association between cholelithiasis and diabetes often are controversial and are mostly based on autopsies or on hospital series. Therefore, we designed a case-control study to determine the prevalence of diabetes mellitus in a group of subjects with gallstones or having undergone cholecystectomy (cases) and compared these with a control group of subjects without gallstones, selected during an epidemiological study performed on a free-living population sample. The subjects were matched for sex, age, and body mass index. We enlisted 336 cases and 336 controls, aged 30 to 69 years. All subjects with fasting glycemic levels of < 140 mg/dL and without a documented history of diabetes were submitted to a simplified oral glucose tolerance test (OGTT). All subjects who underwent OGTT were classified according to the National Diabetes Data Group (NDDG) criteria. The prevalence of diabetes in the subjects affected by gallstone disease was significantly higher than that in controls (11.6% vs. 4.8%; odds ratio [OR], 2.55; 95% confidence interval [CI], 1.39-4.67). Diabetes was more frequent in subjects with gallstone disease than in the control group, even according to sex (18.3% vs. 9.9% for men: OR, 2.03; 95% CI, 0.99-4.2; 9.3% vs. 2.6% for women: OR, 3.85; 95% CI, 1.4-10.6). We conclude that an altered glucose metabolism may increase the risk of developing cholelithiasis in certain subjects.

Adult↗
PubMed1996

Overexpression, one-step purification and characterization of UDP-glucose dehydrogenase and UDP-N-acetylglucosamine pyrophosphorylase.

Two enzymes of the Leloir pathway, UDP-GlcNAc pyrophosphorylase and UDP-Glc dehydrogenase, which are involved in the synthesis of activated sugar nucleotides have been cloned, overexpressed in Escherichia coli, and purified to homogeneity in only one step by chelation-affinity chromatography. The gene KfaC of E. coli K5 was thus demonstrated to encode UDP-Glc DH. Some properties of the cloned enzymes, such as stability, pH dependence, and substrate kinetics, were studied in order to facilitate the use of these enzymes in carbohydrate synthesis, especially in the synthesis of hyaluronic acid.

Amino Acid Sequence↗
PubMed1996

Photodynamic therapy in gynaecological neoplastic diseases.

Since 1982, our department has used photodynamic therapy (PDT) in the treatment of loco-regional recurrences of gynaecological cancers. We have treated 26 patients in this time. In the majority of cases the site of vaginal recurrences was the vaginal vault. The light sources were an Argon-dye laser (Meditec) and, in some cases, a CO2 laser. The light dose ranged between 60 and 500 J cm-2. The photosensitizing drug used was Hematoporphyrin (HP) (Monico Farmaceutici) at the dose of 5 mg kg-1 body weight. Patients were evaluated 45 days after the treatment with a gynaecological examination and after 75-90 days with a vaginal smear. The results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only the patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms at least for 60 days. In this group the complete response rate was 66%. In the curative group, the complete response was a cytological and/or histological absence of lesions. In this group we had 12 CR (70.58%). The survival rate was also evaluated. A significant review of the photodynamic therapy in gynaecological neoplasms has also been done.

Adenocarcinoma↗
PubMed1996

Lipoperoxidase activity of Pityrosporum: characterisation of by-products and possible rôle in pityriasis versicolor.

Modification of pigmentation and damage of melanocytes are characteristic features of skin colonisation of Pityrosporum orbiculare hyphae in pityriasis versicolor (PV). The yeast is lipophylic and lipid-dependent, capable of oxidising unsaturated lipid components of skin surface, i.e., unsaturated fatty acids, cholesterol and squalene (SQ). The oxidation of unsaturated fatty acids gives rise to dicarboxylic acids (DA) which behave, in vitro, as competitive inhibitors of tyrosinase. In this work, we further investigate the oxidase activity of Pityrosporum in vitro, by evaluating (a) the generation of lipoperoxides in cultures supplemented with fatty acids at various degrees of unsaturation; (b) the mechanism of SQ oxidation; (c) the chemical characteristics of some by-products of lipoperoxidation; (d) the formation of peroxisomes in fungal cells. In cultures supplemented with the saturated palmitic acid (C16:0) and monounsaturated oleic acid (C18:1 n-9), low amounts of lipoperoxides were detected by a spectrophotometric test, whereas in cultures supplemented with di-unsaturated linoleic acid (C18:2 n-6), significant concentrations were found. Gas chromatography-mass spectrometry analyses showed the generation of linoleic acid hydroperoxides both in Pityrosporum cultures and following incubation of acetone powder of the fungus with the unsaturated fatty acid, indicating the presence of a lipoxygenase activity in the fungus. In cultures supplemented with linoleic acid plus SQ, and increase of lipoperoxide generation was observed and trans-trans farnesal and squalene epoxides have been identified. Electron microscopic examinations have evidenced peroxisomes in cells grown in the presence of linoleic acid, whereas they were not detected in cultures supplemented with oleic acid and palmitic acid. The metabolic activities of peroxisomes, through the formation of hydrogen peroxide and the subsequent generation of hydroxyl radicals, may account for the peroxidation of SQ, which is not a substrate of lipoxygenase. Following these results, we propose a mechanism for DA generation by Pityrosporum metabolism and hypothesize that the lipoperoxidation process induced by lipoxygenase activity of the fungus may be the key to understanding the clinical appearance of skin manifestation of PV.

Dicarboxylic Acids↗
PubMed1995

Effect of different inhibitors of sterol biosynthesis on both fungal growth and aflatoxin production.

Azole antifungals are reported to interfere with fungal growth by selective impairment of the P-450 dependent 14 alpha-demethylase system key to biosynthesis of ergosterol (ERG), thus leading to the depletion of this sterol in fungal membranes and to the accumulation of methylated precursors. We have investigated whether azole antifungals ketoconazole, miconazole, econazole, or itraconazole were able to modify the sterol and fatty acid patterns of a toxigenic strain of Aspergillus parasiticus, inducing the growth of mycelium depleted of ergosterol (ERG) and rich in less oxidizable sterols. It had been demonstrated that oxidation of ERG is correlated to aflatoxin biosynthesis. However, in this study no alteration of sterol or fatty acid patterns was observed after 7, 14, and 21 days of incubation of A. parasiticus in the presence of sublethal doses of azole antifungals. Specific production of aflatoxin was unaffected. Among the four antifungals tested, itraconazole was the strongest inhibitor of fungal growth and aflatoxin production while ketoconazole was the least effective.

Aflatoxins↗
PubMed1995

Gynecologic cancer recurrences and photodynamic therapy: our experience.

The incidence of locoregional recurrences of gynecological tumors is still a major problem. Many authors suggest that it is the major cause of death in patients affected by cervical-endometrial cancers. The results achieved by retreating these patients with conventional therapies are still unsatisfactory. Since 1982, in our department, we have been using photodynamic therapy (PDT) for treatment of locoregional recurrences in gynecological cancers. We have treated 26 patients. In the majority of the cases, vaginal recurrences were on the vaginal vault. Out of 26 cancers, 17 were epidermoid cancers. Lasers used were the argon dye laser (Meditec) and, in some cases, the CO2 laser. Light dose ranged between 60 and 500 J/cm2. The photosensitizing drug used was hematoporphyrin (HP) (Monico Farmaceutici, Venezia, Italy) at a dose of 5 mg/kg body weight. Patients were evaluated 45 days after treatment with gynecological examination and again after 75-90 days with a vaginal smear. Results were divided into 2 groups: objective and symptomatic. The symptomatic response concerned only patients treated with a palliative aim and, in this case, a complete response (CR) was a complete absence of symptoms for at least 60 days. In this group the complete response rate was 66.6%. In the curative group, the complete response was a cytological and/or histological absence of lesion. In this group we had 12 CR (70.58%). The survival rate of patients treated only with PDT ranged between 3 and 92 months (mean 50.7 months). No major acute or side effects were recorded.

Female↗