0000000000449835
AUTHOR
Maria Concetta Gueli
Similar turnover in the metabolic appenings of central histaminergic system in Down syndrome and Alzheimer disease
Blood levels of homocysteine, cysteine, glutathione, folic acid, and vitamin B12 in the acute phase of atherothrombotic stroke.
Blood levels of total homocysteine (tHcy), cysteine (Cys), total and reduced glutathione (tGSH and rGSH), folic acid (FA), and vitamin B(12) (B(12) change during ischemic stroke as accompaniment of the tissue damage. The relationship between these changes remains scantly investigated. We evaluated the variation of these molecules in the 48 h after acute large artery atherothrombotic stroke (LAAS) and searched for the presence of matched variation of them. The study involved 50 subjects affected by acute LAAS and 49 healthy controls. Plasma levels of tHcy and Cys were significantly higher and serum levels of FA and B(12) and plasma levels of rGSH were significantly lower in the patients than…
Alzheimer's disease: amino acid levels and brain metabolic status.
Abstract To study brain free amino acids and their relation with dementia we measured, by high-performance liquid chromatography (HPLC), the concentration of eight free amino acids, amines and related compounds. We used temporal cortex (TC) samples obtained from 13 Alzheimer’s disease (AD) patients and an equal number of agematched controls (AC). The patterns of free amino acids, amines and related compounds showed significant quantitative changes in AD conditions with respect to healthy ones. In Alzheimer patients, lower levels of GABA were found in the TC (-57 %). Amino acids glutamate (Glu), and aspartate (Asp) concentrations, also appeared significantly reduced in the TC of AD patients …
GSH: A MARKER FOR OXIDATIVE STRESS IN HUMAN CELL CULTURES
GSH: A MARKER FOR OXIDATIVE STRESS IN HUMAN CELL CULTURES Gueli Maria Concetta Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNEC), Università degli Studi di Palermo. Reactive oxygen species (ROS) play an important role in physiological processes, but when being in excess ROS react readily with proteins, lipids, carbohydrates, and nucleic acids, often inducing irreversible functional alterations or even complete destruction. In cells, under physiological conditions, the production and detoxification of ROS are more or less balanced. GSH functions as antioxidant and the oxidative conversion of GSH to GSSG is widely recognized as a reliable index of oxidative stress. The…
Rapid and simultaneous high-performance liquid chromatography assay of polyamines and monoacetylpolyamines in biological specimens
A rapid, resolutive and reproducible reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed for polyamines and acetylpolyamines by adopting pre-column derivatization with benzoyl chloride. In a single run lasting less than 15 min ten polyamines were separated as well as traces of benzoic acid, methylbenzoate and benzoic anhydride. These contaminants, produced during the derivatization reaction, were almost all eliminated by washing steps envisaged in the same procedure. This simple and sensitive method can be applied to routine determination of polyamines in biological samples. A fine application of this procedure to the determination of endogenous content of p…
Fast one-step liquid chromatography determination of purine compounds in blood with photodiode array detector
Differentiation induced by 3-aminobenzamide in human osteosarcoma MG-63 cells is mediated by the inhibition of the Wnt/β-catenin pathway
Sensitivity of human retinoblastoma Y79 cells to Paclitaxel was mediated by aberrant E2F1 expression and p53 accumulation
A NOVEL NONSENSE MUTATION IN THE CETP GENE IN ITALIAN HYPERALPHALIPOPROTEINEMIC SUBJECTS
Tissue transglutaminase expression and homocysteine in T84 human colon carcinoma and mesenchymal stem cells.
Hypoxanthine and purine compounds in plasma from patients with multiple sclerosis and psoriasis
L-DOPA monitoring in treated patients with Parkinson's Disease
Biochimica e Fisiopatologia delle Specie Reattive dell’Ossigeno
Atherothrombotic Stroke: Plasmatic Modification Of Homocysteine and Other Thiols
IL GENE PCSK9: UN NUOVO GENE IMPLICATO NEL CONTROLLO DELLA COLESTEROLEMIA
The distribution of cholesterol plasma is regulated by complex interactions between genes and environmental factors. Mutations of PCSK9 gene seem to modulate the levels of LDL-C. Mutations of PCSK9 gene with gain of function are associated to hypercholesterolemia and mutations with loss of function determine hypocholesterolemia.
Plasma Glutathione Levels During Aging
Blood lipids, homocysteine, stress factors, and vitamins in clinically stable multiple sclerosis patients
Abstract Multiple Sclerosis (MS) patients present a decrease of antioxidants and neuroprotective and immunoregulatory vitamins and an increase of total homocysteine (tHcy), cholesterol (CHL), HDL-cholesterol, and of cellular stress markers, variably associated with the different phases of the disease. We compared the blood levels of uric acid, folic acid, vitamins B12, A, and E, tHcy, CHL, HDL-cholesterol, and triglycerides in forty MS patients during a phase of clinical inactivity with those of eighty healthy controls, matched for age and sex. We found higher levels of tHcy (p = 0.032) and of HDL-cholesterol (p = 0.001) and lower levels of vitamin E (p = 0.001) and the ratio vitamin E/CHL …
Cysteine plasma levels in normal pregnancy after folic supplementation
Some kinetic properties of the chick embryos nucleoside phosphotransferase
Retinol oxidation to retinoic acid in human thyroid glandular cells.
Abstract Retinoic acid is regarded as the retinol metabolite that controls proliferation and differentiation of epithelial cells. In the present study, we investigated the potential role of xanthine dehydrogenase (XDH) in retinoic acid biosynthesis in human thyroid glandular cells (HTGC). In particular, we observed that cellular retinoids binding proteins (CRBPs) are also implicated in the biosynthetic pathway leading to retinoic acid formation in primary cultures of HTGC, as we have already reported for human mammary epithelial cells (HMEC). After partial protein purification, the enzyme responsible for retinoic acid biosynthesis was identified and quantified as XDH by immunoassay, by its …
TERAPIA CON STATINE IN PAZIENTI SICILIANI AFFETTI DA IPERLIPIDEMIA FAMILIARE COMBINATA
Familial combined hyperlipidemia (FCHL) is the most frequent genetic hyperlipidemia. FHCL is associated with high prevalence of cardiovascular disease. In this study we selected 208 patients affected by FHCL and evaluated the efficacy of the lipid-lowering statin therapy using different statins available in the market. The results show that the percent of patients reaching the therapeutic goal ranges from 19.7 % (LDL-C <100 mg/dL) to 50.9% (LDL-C <130 mg/dL) and from 16.9 % (non HDL-C <130 mg/dL) to 46.6 % (non HDL-C <160 mg/dL) according to the different ATPIII-NCEP-guidelines cut offs. In conclusion the statin monotherapy is only partly effective in the management of FCHL therapy
Genomic Analysis by Chromatin Immunoprecipitation Assay (CHIP)
Plasma Cysteine and Homocysteine concentrations in pregnant and nonpregnant women with controlled folate intake
Serum acid homocysteine, oxidative stress markers and vitamins in multiple sclerosis
Free amino acid levels and brain human metabolic status in Alzheimer's disease and Down's syndrome
Homocysteine and S-adenosylated metabolites in cardiovascular disease
A major unanswered question is whether direct cellular toxicity of homocysteine (Hcy) is causally involved in cardiovascular disease (CVD) in humans or whether homocysteinemia is simply a passive and indirect indicator of a more complex mechanism. Alternatively or additionally, the association between Hcy and CVD may result from its metabolic precursor S-adenosyl-Hcy (SAH), or from the altered ratio of S-adenosylmethionine SAM/SAH. This competition is based on the known effects of these adenosylated metabolites on cellular methylation, disturbances of which may lead to endothelial dysfunction and/ or CVD. Thus, it is of great significance to know how these adenosylated metabolites (SAM, SAH…
Retinoid dynamics in chicken eye during pre- and postnatal development.
Changes in the steady state level of retinols, retinaldehydes and retinyl esters in the trans and 11-cis forms and trans retinoic acid were measured in whole chicken eye during development from day 6 in ovo to day 3 post-hatch. These retinoids, quantified by different HPLC systems, were detected in this time sequence: trans-retinol and trans-retinyl esters in the first week in ovo, 11-cis-retinol in the second week. The highest level of 11-cis-retinaldehyde and 11-cis-retinyl esters was reached at the end of development in ovo; however, their levels increased further after hatching. The retinoic acid level decreased at the end of the first week, rising again at the end of the second week. T…
Changes of homocysteine and related compounds in Down syndrome
Taurine in the interphotoreceptor matrix
TAURINE IN THE INTERPHOTORECEPTOR MATRIX Gueli Maria Concetta Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNEC), Università degli Studi di Palermo Taurine (Tau) is the most abundant amino compound free in the retina. It is concentrated in the photoreceptor inner segment, in the outer nuclear layer and in the synapses. The retina synthesizes and receives Tau from choroidal blood via the pigment epithelium (PE). The high content in the retina suggest the possibily of verifying whether it was present in the interphotoreceptor matrix (IPM), which occupies the subretinal space. In this study we have determined the Tau level in the IPM, separating it from other soluble ami…
SIMULTANEOUS DETERMINATION OF ATP, ITS METABOLITES AND NAD+ IN BLOOD BY HPLC WITH PHOTODIODE ARRAY DETECTOR
SIMULTANEOUS DETERMINATION OF ATP, ITS METABOLITES AND NAD+ IN BLOOD BY HPLC WITH PHOTODIODE ARRAY DETECTOR Gueli Maria Concetta, Cusimano Vincenza, Lo Re Marianna, Giuseppe Salemi Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNEC), Università degli Studi di Palermo. Nucleotides are major high-energy phosphate carriers, subunits of nucleic acids and precursors for the synthesis of nucleotide cofactors such as NAD+ and SAM. The study of purine nucleotides metabolism is very important topic for a right understanding for the cellular life. Living cells rely on ATP for growth, differentiation, and response to physiological stimuli and environmental stress. We propose a fa…
Biochimica clinica dello stress ossidativo
Poly(ADP-ribose) polymerase (PARP): The advantages of using PARP inhibitors to modulate its activity in pathological conditions and to kill cancer cells
Brain amino acid levels are altered in Alzheimer's disease
Analysis of a soluble lipid-protein complex carrying endogenous 11-cis retinaldehyde from bovine retinal pigment epithelium.
A soluble lipid-protein complex in bovine retinal pigment epithelium is shown to carry endogenous 11-cis retinaldehyde, in the extent of 15% of the total 11-cis retinaldehyde found in this tissue. The complex, analyzed with respect to its chemical composition, exhibits a lipid composition close resembling the lipid composition of the rod outer segment membrane; the SDS-PAGE evidences the presence of a number of protein bands, two of which of 34 and 27 kDa appear glycoproteins. Finally, the lipid-protein complex exhibits a discrete level of a Cathepsin D-like protease activity. From the above, the possibility is discussed that the soluble lipid-protein complex could represent some phagolysos…
Hypoxanthine, xanthine, and uric acid in plasma from patients with multiple sclerosis and psoriasis.
Microscopy Fluorescence and Apoptosis Studies
High turnover rate of central histaminergic system in patients with Down syndrome and Alzheimer disease
HIGH TURNOVER RATE OF CENTRAL HISTAMINERGIC SYSTEM IN PATIENTS WITH DOWN SYNDROME AND ALZHEIMER DISEASE Maria Concetta Gueli Dipartimento di Biomedicina Sperimentale e Neuroscienze Cliniche (BioNEC), Università degli Studi di Palermo It is well confirmed that a strong relationship exists between Down’s syndrome (DS) and Alzheimer’s disease (AD). Neurochemical investigations reported that many central neurotransmitter systems are similarly affected in aging Down and in Alzheimer patients, respectively. Airaksinem et al. (1) found numerous neurofibrillary tangles in the tuberomammillary area of the hypothalamus, where cell bodies of histaminergic neurons are located. While Mazurkiewicz-Kwilec…
Kinetic properties of a nucleoside phosphotransferase of chick embryo
1. A nonspecific nucleoside phosphotransferase (nucleotide : 3'-deoxynucleotide 5'-phosphotransferase, EC 2.7.1.77), purified from chick embryos, catalyzes the transfer of phosphate ester from a nucleotide donor to a nucleoside acceptor. 2. The enzyme exhibits sigmoidal kinetics with respect to nucleoside monophosphate donors, but with respect to nucleoside di- or triphosphate donors and nucleoside acceptors hyperbolic kinetics were obtained. 3. The nucleoside phosphotransferase of chick embryo is unstable to heat and is protected from inactivation by a large number of nucleosides. 4. Nucleoside di- and triphosphates lower both the concentration of nucleoside monophosphates required for hal…
Xanthine dehydrogenase processes retinol to retinoic acid in human thyroid epitelial cells
Homocysteine in human colon carcinoma cells
Plasma homocysteine levels in patients with metabolic syndrome
Central histaminergic system in patients with Down's syndrome and Alzheimer's disease
Le ipocolesterolemie primitive
Hypobetalipoproteinemia (HBL) is characterized by cholesterol levels below the 5th percentile of the population distribution. Familial HBL (FHBL) is characterized by an inherited HBL trait within a family. In the last years gene defects underlying some cases of FHBL, but not all, have been identified. The molecular basis of some gene defect and the clinical onset of FHBL are presented in this paper.
ELABORATION OF CURCUMIN INTO DIKETONE MODIFIED ANALOGUES DEVOID OF NUCLEOPHILIC ADDITION CAPABILITY; IMPLICATIONS FOR THEIR ANTITUMOR AND CHEMOSENSITIZING ACTIVITIES
Curcumin (CUR), a polyphenolic compound extracted from Curcuma longa L.,can beconsidered as a good lead compound for the design of new drugs for the treatment of cancer and other therapeutic purposes. CUR is endowed with a diketone function, which appears to be important for its antitumor activity: also depending on the dose, the compound may show complex either pro-oxidant or anti-oxidant effects, which both may, at least in part, be linked to this structural moiety. In the lower concentration, "chemopreventive", range, CUR behaves mainly as an antioxidant; at higher concentrations, the a, b-unsaturated 1,3-diketone, as a Michael acceptor, can form adducts with the –SH groups and generate …
Purine metabolism and multiple sclerosis: pattern varies according to disease stage and clinical form
Retinyl ester hydrolases in retinal pigment epithelium.
In bovine retinal pigment epithelium membranes we have found three hydrolases which were active against trans-retinyl palmitate. This was possible by assaying different subcellular fractions as a function of pH in the range 3-9. Detection of these activities has been favored by the use in the enzyme assay of Triton X-100, which has an activating effect up to a concentration of 0.03% at a detergent-protein ratio of about 1.5-3.0. Apparent kinetic parameters for the retinyl ester hydrolases have been determined after a study of the optimization of assay conditions. Vmax values for hydrolases acting at pH 4.5, 6.0, and 7.0 were, respectively, 156, 55, and 70 nmol/h/mg. To identify the subcellu…
LE IPERCOLESTEROLEMIE PRIMITIVE
Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitizing activities.
Curcumin (CUR) can be considered as a good lead compound for the design of new anticancer drugs. Further, structure-activity relationship studies may clarify the importance of the redox activities in the antitumor effects of the drug. We have elaborated the alpha,beta-unsaturated 1,3-diketone moiety of CUR into the isoxazole (ISO) and pyrazole (PYR) derivatives. These derivatives should be much less prone to nucleophilic addition than CUR and benzyl mercaptan addition analyses showed that indeed they do not form isolable conjugated products. When compared with CUR, ISO and PYR exhibited increased cell growth inhibitory and pro-apoptotic effects in liver cancer HA22T/VGH cells as well as in …
SERUM URIC ACID, HOMOCYSTEINE, OXIDATIVE STRESS MARKERS AND VITAMINS IN MULTIPLE SCLEROSIS.
Distribution of homocysteine and cysteine in plasma lipoprotein fractions
S-thiolation of plasma proteins have been detected in healthy humans, in patients with cardiovascular diseases and it is a recurrent phenomenon in oxidative stress elicited by reactive oxygen species. The low-molecular-weight aminothiols homocysteine (Hcy) and cysteine (Cys) can exist in the plasma either free or bound to thiol-combining groups, many of which are present in proteins (Pb), particularly albumin. Recent studies have demonstrated that also plasma lipoproteins (LP) are susceptible to form disulfide-linked products with Hcy and Cys and that the N-homocysteinylation is accompanied by structural and functional alteration and could increase the atherogenicity of LDL. However, the me…
Disturbances of one-carbon metabolism in treated patients with Parkinson's Disease
Plasma aminothiol concentrations in pregnant women with controlled folate intake
Impairment of Methylation cycle in treated patients with Parkinson's disease
L-3,4-dihydroxyphenylalanine (L-DOPA) alone or in combination with a peripheral dopa decarboxylase inhibitor (DDI) is the most effective therapeutic agent to improve motor function in most of patients with Parkinson's disease (PPD). However, chronic L-DOPA therapy is associated with of side-effects arising particularly during long-term therapy. Only a small percentage of an exogenous dose of L-DOPA is converted into dopamine (DA) in the brain. The majority is either decarboxylated in peripheral tissues by aromatic amino acid decarboxylase (AAD) to DA, which does not cross the blood-brain barrier, or is O-methylated by catechol-O-methyltransferase (COMT) in both peripheral and brain tissue t…
Blood lipid, homocysteine, uric acid and vitamins in clinically stable Multiple Sclerosis patients
A decrease of antioxidants, of neuroprotective and immunoregulatory vitamins and an increase of total-Homocysteine, Cholesterol, HDL-cholesterol, and of cellular stress markers [1] was reported in patients affected by Multiple Sclerosis. Recently, considering their unreliability, mainly due to the variability of the samples investigated, the attention focused on clinical relapse that results associated to a decrease of Uric acid and an increase of Cholesterol and stress markers. Aim. To identify the biochemical status during Multiple Sclerosis (MS) in a phase of clinical stability (PCS), we compared the blood levels of Urico acid (UA), Folic acid (FA), vitamins B12, A, and E, total-Homocyst…
Correlation between the effects of retinoic acid and dexamethasone on liver tyrosine aminotransferase
A single dose of 50 microg of trans-retinoic acid administered to rats significantly raised the level of hepatic tyrosine after a few hours. This effect was compared with that of dexamethasone and a possible correlation between these effectors was also investigated. An equal increase in enzyme activity level caused by retinoic acid was observed in adrenalectomized rats, leading to the suggestion that the effect of retinoic acid on liver tyrosine aminotransferase is independent of glucocorticoids. However, the study of the binding activity of the liver nuclear glucocorticoid receptors vs dexamethasone showed that this activity is favoured by retinoic acid, whereas no variation was evidenced …
Purine metabolism and Multiple Sclerosis: different pattern according to different disease stage and different clinical form.
P422 Purine metabolism and multiple sclerosis: pattern varies according to disease stage and clinical form G. Salemi, M. Gueli, V. Cusimano, M. Lo Re, V. Lo Re, M.A. Mazzola, S. Realmuto, P. Ragonese, G. Savettieri University (Palermo, IT) Background: Serum concentration of uric acid (sUA) was variably associated with Multiple Sclerosis (MS). Many papers reported lower sUA in MS patients respect to healthy controls, expecially in course of relapse. This lower sUA was considered as a marker of oxidative stress. However, this association was not confirmed by many other papers. Recently, an increase in the concentration of sUA, hypoxanthine, xanthine, and sum of oxypurine (sPU) was reported in…
A simple assay to determine total homocysteine and other thiols by high pressure liquid chromatography
Glutathione: a marker for oxidative stress in human cell cultures
Xanthine oxidase catalyzes the synthesis of retinoic acid
Milk xanthine oxidase (xanthine: oxygen oxidoreductase; XO; EC 1.1.3.22) was found to catalyze the conversion of retinaldehyde to retinoic acid. The ability of XO to synthesize all trans-retinoic acid efficiently was assessed by its turnover number of 31.56 min-1, determined at pH 7.0 with 1 nM XO and all trans-retinaldehyde varying between 0.05 to 2 microM. The determination of both retinoid and purine content in milk was also considered in order to correlate their concentrations with kinetic parameters of retinaldehyde oxidase activity. The velocity of the reaction was dependent on the isomeric form of the substrate, the all trans- and 9-cis-forms being the preferred substrates rather tha…