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Biomedical subjects

S Ruggieri

Publications and source records attributed to S Ruggieri.

At least 55 records · Page 3Linked to original sources
PubMed1994

Clinical implications of sustained dopaminergic stimulation.

Fluctuations in motor performance are the major problems in chronic management of Parkinson's disease. Most of these fluctuations reflect the decline of levodopa availability. As a consequence, levodopa dosage might be increased and the interdose interval progressively shortened. The postsynaptic dopamine receptors at this point are exposed to a nonphysiologic shift in dopamine level, which may induce changes at the receptor site and contribute to the appearance of "on-off" phenomena and dyskinesias. We compared a group of 18 patients treated for 60 consecutive months with continuous subcutaneous lisuride infusion with a group of 20 patients treated with conventional oral levodopa treatment. The clinical evaluations performed during the study showed in the lisuride group only a worsening of dyskinesias, whereas the other symptoms remained unchanged. In the other group the evaluation scores showed a significant worsening of all long-term treatment complications. The slow-release preparations of levodopa may ensure a more continuous dopaminergic stimulation than standard formulations. However, the use of these compounds is difficult in severely fluctuating patients because the lack of a plasma peak level usually leads to a very long delay before patients turn "on." We studied the pharmacokinetic and clinical effects of the two slow-release preparations of levodopa [Madopar HBS and Sinemet controlled-release (CR)] and a combination of Sinemet CR plus standard Sinemet in 13 fluctuating parkinsonian patients. The results of this study show that the combination of standard Sinemet and Sinemet CR ensures a more prolonged clinical effect with a very short latency to the "on" phase.

Aged↗
PubMed1993

Complex gangliosides modulate the integrin-mediated adhesion in a rat hepatoma cell line.

In this study, we investigated whether complex gangliosides influence cell adhesion by modulating the activity of integrin receptors. Our experimental model was represented by CMH5123 cells, a line of neoplastic hepatocytes derived from the minimal deviation Morris hepatoma 5123c of the rat, which adhered to substrata coated with fetal calf serum (FCS) by an integrin-mediated mechanism, being vitronectin the specific serum protein which sustained cell adhesion. We found that ganglioside depletion, obtained by inhibiting complex ganglioside biosynthesis, was accompanied by a reduction of cell adhesiveness to FCS-coated substrata. Integrins appeared to mediate the effect of ganglioside depletion on cell adhesiveness. In fact, sensitivity to the integrin inhibitor GRGDSPC peptide was ten times higher in ganglioside-depleted cells compared to control cells. Moreover, growth of ganglioside-depleted CMH5123 cells in media supplemented with complex gangliosides restored the cell sensitivity to the integrin inhibitor to the same level as that found in control cells. Furthermore, ganglioside depletion of CMH5123 cells decreased the affinity of vitronectin receptors for vitronectin without modifying their number, affinity of vitronectin receptors was re-established in ganglioside-depleted cells by supplementing their growth media with complex gangliosides. In conclusion, these results support the participation of gangliosides to cell adhesion as modulators of integrin receptors.

Amino Acid Sequence↗
PubMed1993

Effect of phosphatidylcholine structure on the adenylate cyclase activity of a murine fibroblast cell line.

To determine which structural characteristics of membrane phospholipids influence adenylate cyclase activity, we measured basal and sodium fluoride-or forskolin-stimulated activity in a murine fibroblast cell line, i.e., Balb/c3T3 cells grown in media supplemented with fetal calf serum (FCS), lipid-depleted FCS (LD-FCS) or LD-FCS complexed with different phosphatidylcholine (PC) molecular species. Cells grown in the presence of LD-FCS showed a substantial decrease in their basal and NaF-stimulated adenylate cyclase activities; however, their forskolin-stimulated activity was not altered, suggesting that the enzyme's catalytic site is not affected by changes in membrane lipids. Media supplemented with different LD-FCS/PC complexes were shown to prevent the LD-FCS-mediated reduction of basal and NaF-stimulated adenylate cyclase activity to different extents. Addition of cis-9-16:1, cis-9-18:1/cis-9-18:1 or cis-9-18:1/cis-9,12-18:2 sn-glycerophosphocholine (GPC) completely restored adenylate cyclase activity, while cis-11-18:1/cis-11-18:1 GPC was not effective and only a partial recovery was observed with 16:0/16:0, 16:0/cis-9-18:1 and trans-9-18:1 GPC. Considering the structural features of these seven PC molecular species, the findings suggest that an optimal lipid environment is conferred to the enzyme by the presence of two cis double bonds, each located in delta 9 position of the PC acyl chains. The limited effect of cis-9-16:1/cis-9-18:1 GPC and cis-9-18:1/cis-9-16:1 GPC suggests that an equal length of the terminal hydrocarbon chains extending beyond the delta 9 double bonds is also important.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗
PubMed1992

Nuclear matrix-associated NMN adenylyltransferase activity in human placenta.

This paper presents data about the presence of the NMN adenylyltransferase at the nuclear matrix level of human placenta nuclei. It was found that 40-45% of the activity (depending on the extraction procedure) referred to the total nuclear NMN adenylyltransferase was tightly associated with this subnuclear compartment. The matrices purified by two different procedures exhibited DNA, RNA and protein contents comparable with those described in literature. Extensive digestion of human placenta nuclei with DNase I was not able to solubilize the NMN adenylyltransferase activity. Therefore, the data we present are consistent with the conclusion that a part of the total nuclear NMN adenylyltransferase is associated with the nuclear matrix.

Cell Fractionation↗
PubMed1992

Intravenous boluses and continuous infusions of L-dopa methyl ester in fluctuating patients with Parkinson's disease.

In six patients with Parkinson's disease exhibiting severe "on-off" phenomena, a 200-mg intravenous bolus of either L-DOPA or of its methyl ester were equally effective in reversing motor deficits, although the duration of action of the methyl ester was shorter. There were no marked differences in pharmacokinetic parameters for L-DOPA plasma levels after administration of L-DOPA and the methyl ester. In three patients, optimal infusion rates for the maintenance of mobility were established for L-DOPA and L-DOPA methyl ester. Both drugs were able to maintain patients "on" throughout a 12-h infusion period. However, on average the optimal infusion rate of L-DOPA methyl ester was 2.7 times greater than that for L-DOPA. There was no marked difference in the plasma levels of L-DOPA achieved, but 3-O-methyl DOPA levels increased more after infusion of L-DOPA methyl ester than after infusion of L-DOPA itself. The half-life of elimination and volume of distribution of L-DOPA formed from the methyl ester were markedly increased compared with values obtained after either an intravenous bolus of methyl ester or after an intravenous infusion of L-DOPA itself. An intravenous bolus of L-DOPA methyl ester produces an equivalent magnitude of clinical response to the same dose of L-DOPA. However, higher optimal infusion rates of methyl ester than L-DOPA are required to produce continuous effect. The pharmacokinetic handling of L-DOPA methyl ester given by intravenous infusion may differ from that of L-DOPA when given by the same route.

Aged↗
PubMed1992

NAD biosynthesis in human placenta: purification and characterization of homogeneous NMN adenylyltransferase.

Nicotinamide mononucleotide (NMN) adenylyltransferase has been purified to homogeneity from human placenta. The purification procedure consists of several chromatographic steps, including dye-ligand, adsorption, and hydrophobic interaction chromatography. The final enzyme preparation is homogeneous as judged by a single silver stainable band on both nondenaturating and denaturating polyacrylamide gels. The native enzyme shows a molecular weight of about 132,000, as determined by gel filtration on a Superose 12 HR 10/30 fast protein liquid chromatography column. The protein possesses a quaternary structure and is composed of four apparently identical M(r) 33,000 subunits. Isoelectrofocusing experiments give multiple pI values ranging from pH 4.7 to 6.6. Optimum pH study shows a plateau extending from pH 6.0 to pH 9.0. Km values for NMN, ATP, NAD+, and PPi are 38, 23, 67, and 125 microM, respectively. Kinetic analysis reveals a behavior consistent with an ordered sequential Bi-Bi mechanism. Among several metabolites tested only ADP-ribose and beta-NMNH were found to significantly inhibit the enzyme activity.

Amino Acids↗
PubMed1992

The clinical efficacy of single morning doses of levodopa methyl ester: dispersible Madopar and Sinemet plus in Parkinson disease.

For many patients with Parkinson disease and levodopa-related motor fluctuations, the latency to onset of action of a single dose of a levodopa preparation may be both long and variable. In an effort to find a more rapidly acting and reliable preparation of levodopa, we therefore studied the efficacy of single doses of an oral solution of 250 mg of levodopa methyl ester (ME) with benserazide, 50 mg and of a molar equivalent dose of dispersible Madopar (DM) (50/200) in 13 patients in the fasting state after overnight drug withdrawal. The response of seven of these patients was compared to that after two Sinemet 25/100. The latency to "on" was equally fast with ME and DM, and significantly faster than after standard Sinemet. The duration of "on" was similar with all three. Because of this more rapid relief of "off" periods, both ME and DM offer a potential clinical advantage over standard preparations of levodopa.

Benserazide↗
PubMed1992

Reduction of the metastatic potential of a RSV-transformed fibroblastic line (B77-AA6 cells) upon transplantation in essential fatty acid-deficient mice.

Metastatic dissemination has been shown to be influenced by dietary lipids. In particular, diets enriched with linoleic acid have been consistently found to be effective in enhancing the metastatic potential of murine mammary tumors. This study explored whether an essential fatty acid (EFA)-deficient host can affect the capacity of a tumor to metastasize to the lung. Tumors were developed by subcutaneously injecting high metastatic B77-AA6 cells (a subclone isolated from the Balb/c 3T3 cells transformed by the B77 strain of RSV) into syngeneic mice which had been fed either a control or an EFA-deficient diet for 9 weeks. EFA deficiency did not modify the incidence, latency and growth rate of primary tumors developed from B77-AA6 cells, while it markedly reduced their capacity to reproduce lung macro- and micrometastases. These findings demonstrate that physiological levels of EFA are important for a tumor to metastasize in secondary organs.

3T3 Cells↗
PubMed1991

Purification of human cytidine deaminase: molecular and enzymatic characterization and inhibition by synthetic pyrimidine analogs.

Cytidine deaminase has been purified to homogeneity from human placenta by a rapid and efficient procedure consisting of affinity chromatography followed by hydrophobic interaction chromatography. The final enzyme preparation showed a specific activity of 64.1 units/mg, corresponding to about 46,000-fold purification with respect to the crude extract. The enzyme is a 52-kDa oligomeric protein composed of four apparently identical subunits. The acidic isoelectric point is 4.5. The enzyme's stability is strictly dependent on the presence of reducing agents. Amino acid analysis reveals the presence of five thiol groups per monomer which cannot be titrated by Ellman's reagent in the native enzyme. However, the presence of sulfhydryl groups involved in the catalytic activity was evidenced by the inhibition exerted by p-chloromercuribenzoate and heavy metal ions. In addition, the protection effected by the substrate against the p-chloromercuribenzoate inhibition and the competitive inhibition exerted by 5-(chloromercuri)cytidine suggest the presence of a thiol group(s) in the catalytic site of the enzyme. pH studies have shown that the rapid decline of activity occurring at pH 4.5 might result from the protonation of the pyrimidine ring at the N-3 position. The enzyme catalyzes the deamination of cytidine, deoxycytidine, and several analogs, including antineoplastic agents, thus abolishing their pharmacological activity. Therefore, several pyrimidine nucleoside analogs have been tested as potential inhibitors of the enzyme. The competitive inhibition exerted by cytidine analogs having the ribose moiety replaced by aliphatic chains is interesting.

Amino Acids↗
PubMed1991

Use of N-acetylpsychosine as internal standard for quantitative high-performance liquid chromatographic analysis of glycosphingolipids.

The use of N-acetylpsychosine as an internal standard for the quantitative high-performance liquid chromatography (HPLC) of p-nitrobenzoyl derivatives of glycosphingolipids is described. It is suitable because the chromogen reacts on equimolar basis with both N-acetylpsychosine and sample glycosphingolipids. The use of N-acetylpsychosine as an internal standard was validated by determining the glycosphingolipid content of a system of metastatic variants selected from a murine fibrosarcoma line (T3 cells). Reproducible results were obtained throughout several quantitative analyses of cellular glycosphingolipids and it was possible to determine the glycosphingolipid content of as few as 5 x 10(6) cells.

Animals↗
PubMed1991

Presence of NAD pyrophosphorylase in skeletal muscle in dystrophic mice.

NAD pyrophosphorylase (ATP:NMN adenylyltransferase) activity has been measured in the skeletal muscle of dystrophic mice. The amount of this enzyme in the dystrophic mice, as determined by three different methods, was about one half of that in the controls. In addition, the concentration of ATP was too low to be detected in crude extracts of dystrophic mouse skeletal muscle, which were prepared using Tris buffer alone or Tris buffer containing either 3 M KCl, or 1 mM PMSF.

Adenosine Triphosphate↗
PubMed1991

Lectin reactivity of murine fibrosarcoma lines with a different metastatic potential.

Lectins are suitable tools for investigating the glycoconjugate characteristics of metastatic cells. In the present study, we investigated whether there were differences between high metastatic T3 cells and a low metastatic isolate in their reactivities to several lectins specific for galactosyl and sialyl groups. Analysis of reactivity of the two cell lines to wheat germ agglutinin revealed a complex pattern. In fact, T3 cells had high-affinity, neuraminidase-resistant as well as low-affinity, neuraminidase-sensitive receptors. Instead, the low metastatic isolate showed only high-affinity receptors, both neuraminidase-resistant and neuraminidase-sensitive The two cell lines reacted similarly to galactose-specific lectins. These findings indicate that sialyl groups, rather than galactosyl groups, affect the metastatic behavior of our cell system.

Animals↗
PubMed1991

The clinical efficacy of oral levodopa methyl ester solution in reversing afternoon "off" periods in Parkinson's disease.

We compared the efficacy of a single dose of an oral solution of levodopa methyl ester (ME) to that of standard levodopa, in the form of a single dose of Madopar, in reversing afternoon "off" periods in 12 patients with Parkinson's disease (PD). The highly soluble ME solution led to a significantly more rapid reversal of "off" periods. This preparation may therefore convey a clinical advantage in patients experiencing motor fluctuations whilst taking multiple daily dosages of levodopa, particularly in those with long or highly variable latency to the next "on" period.

Administration, Oral↗