[On-off phenomena in Parkinson's disease. Continuous dopaminergic stimulation].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Ruggieri.
Explore the source record for details and available documents.
Lipid components influence several cell surface properties that are critical in different stages of the metastatic process. In this study, we examined whether the different lung-colonizing potential of B16-F1 and B16-F10 melanoma cells could be related to a characteristic lipid profile. The lipid analyses, carried out on the same cell cultures used for the assay of lung-colonizing potential, revealed characteristics in the lipid composition of both B16-F1 and B16-F10 melanoma cells that are common to other systems of malignant cells: a high level of 18:1 associated with low proportions of polyunsaturated fatty acids in phospholipids, accumulation of ether-linked lipids and absence of complex gangliosides. The two B16 melanoma variants differed significantly only with respect to ether-linked lipids, due to a higher level of alkyl-PC in B16-F10 than in B16-F1.
Verbal, visuospatial and motor functions were studied in eight Parkinsonian patients both during levodopa stimulated and unstimulated state and in eight matched, untreated, healthy controls. Profound changes in patients' motor status were accompanied by relatively selective effects on delayed verbal memory, a function which was also most impaired compared with controls. With dopaminomimetic therapy, tests of delayed verbal memory consistently improved, but did not reach control performance levels. These results could indicate a functional impairment in the mesocortical dopamine system, which can be attenuated, but not entirely corrected, by dopaminomimetic therapy.
Friend erythroleukemia cells were induced to differentiate by dimethyl sulfoxide (DMSO) and hexamethylene-bis-acetamide (HBMA) in order to investigate whether their lipid characteristics, common to other systems of transformed cells, revert to a normal differentiation pattern. DBA/2 mouse erythrocytes were examined as a model of terminal differentiation in erythroid lineage. Variants of erythroleukemia cells not inducible to erythroid differentiation by DMSO and HMBA were also used in this study, in order to test whether lipid modifications occurring in differentiated erythroleukemia cells were related to the differentiation process or caused by specific effects of the inducers. Friend erythroleukemia cells showed the same lipid characteristics as those found in other transformed cell types. That is, a high level of ether-linked lipids and low percentages of long chain polyunsaturated fatty acids along with an accumulation of monoenoic fatty acids in phospholipids. These lipid characteristics remained unchanged when erythroleukemia cells were induced to differentiation by either DMSO or HMBA. However, other lipid components of erythroleukemia cells, e.g., phosphatidylethanolamine and triglycerides, were affected by erythroid differentiation. There were also changes of some lipid components of erythroleukemia cells, such as cholesteryl esters, which were related to specific effects of the inducers. Both DMSO- and HMBA-resistant variants differed from the inducible erythroleukemia cells, mainly in their ether-linked phospholipid pattern.
Explore the source record for details and available documents.
NAD pyrophosporylase has been purified to homogeneity from baker's yeast. The purification procedure is relatively simple and consists of high salt extraction of enzyme activity, precipitation with polyethylenimine followed by ion exchange and by ligand chromatography separations. The final enzyme preparation is homogeneous as judged by a single Coomassie blue-stainable band when run on non-denaturing and denaturating polyacrylamide gels. The native enzyme shows a molecular weight of about 200,000 calculated by gel filtration and sucrose gradient centrifugation. The protein possess quaternary structure and is composed by four apparently identical Mr 50,000 subunits. The absorption spectrum shows a maximum at 280 nm and a minimum at 253 nm. Isoelectric point is 6.2. Amino acid composition shows the presence of 28 half-cystine residues, in agreement with the results obtained by titrating the enzyme in denaturing conditions with Ellman's reagent upon previous incubation with sodium borohydride. NAD pyrophosphorylase is a glycoprotein containing 2% sugar, 2 moles of alkali-labile phosphate per enzyme mol, and 1 mol of adenine moiety per enzyme mol. Therefore the possibility that the enzyme is ADP-ribosylated exists. Km for ATP, NMN and NaMN are 0.11 mM, 0.19 mM and 5 mM respectively. Kinetic analysis reveals a behaviour which is consistent with an ordered sequential Bi-Bi mechanism. pH optimum is in the range 7.2-8.4.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Nicotinamide mononucleotide (NMN) adenylyltransferase has been purified to homogeneity from baker's yeast crude extract. The purification procedure is relatively simple and consists of high-salt extraction of enzyme activity and precipitation with poly(ethylenimine), followed by ion-exchange and dye ligand chromatography separations. The final enzyme preparation is homogeneous as judged by a single Coomassie blue stainable band when run on nondenaturating and denaturating polyacrylamide gels. The native enzyme shows a molecular weight of about 200 000, calculated by gel filtration and sucrose gradient centrifugation. The protein possesses quaternary structure and is composed of four apparently identical Mr 50 000 subunits. The absorption spectrum shows a maximum at 280 nm and a minimum at 253 nm. The isoelectric point is 6.2. Amino acid composition analysis shows the presence of 28 half-cystine residues. The same result has been obtained by titrating the enzyme in denaturating conditions with Ellman's reagent after incubation with sodium borohydride. NMN adenylyltransferase is a glycoprotein containing 2% sugar, 2 mol of alkali-labile phosphate per mole of enzyme, and 1 mol of adenine moiety per mole of enzyme. Therefore, the possibility that the enzyme is ADP-ribosylated exists. The Km values for ATP, NMN, and nicotinate mononucleotide are 0.11 mM, 0.19 nM, and 5 mM, respectively. Kinetic analysis reveals a behavior that is consistent with an ordered sequential Bi-Bi mechanism. The pH optimum is in the range 7.2-8.4.
150 children with Rolandic paroxysmal epilepsy (RPE) aged 3 to 12 years were followed up clinically and by EEG for 16 years. Antiepileptic drugs were administered initially for 2 years and then suspended for 6-12 months. Treatment was resumed in the 29 patients who had seizures during the drug-free interval and was maintained for a further 5 years. 80.6% of all patients were in clinical remission after the 2-year treatment period. Some patients had seizures while on drugs, others during the drug-free interval. Seizure frequency declined with age. No seizures occurred after the age of 14 or in the 8 years following final discontinuation of drug therapy. The need for prolonged drug treatment is therefore questioned.
A multicenter trial was conducted at 9 Neurology Departments to evaluate the action of L-Deprenyl, a specific monoamine oxidase-B inhibitor, combined with L-Dopa in the treatment of Parkinson disease. In all, 76 patients were treated, 33 women and 43 men, on stable treatment with L-Dopa+ aromatic decarboxylase inhibitors (DI) for at least 6 months. After a 50% reduction of the L-Dopa dose, all received L-Deprenyl 5 mg twice daily for 35 day. The combined treatment resulted in a definite improvement in rigidity, bradykinesia and, most of all, tremor. Further, at the end of treatment fewer patients had depressive symptoms and the total daily number of hours of wellbeing and normal movement increased. 12 patients presented modest side effects, in no case serious enough to warrant suspension of treatment. The trial shows that with the L-Deprenyl + L-Dopa combination the dose of L-Dopa needed to control the disease can be drastically reduced.
The classical treatment of Parkinson's disease (PD) using L-dopa plus a peripheral decarboxylase inhibitor (DI) often leads after 3-5 years to the onset of the so-called long-term L-dopa syndrome (LTS). LTS could depend on the chronic overload of L-dopa + ID and could be due to a consequent "receptor disease" and derangement of the neuronal functionality mainly in regard to the enzymatic chains, storage mechanisms and hyperactivity of the monoamine oxidase type B (MAO B). Deprenyl is a selective MAO-B inhibitor thought to be able to slow down the catabolism of dopamine and therefore to allow a decrease of the therapeutic regimen of L-dopa while in the meantime to obtain a more stable plasma and tissue levels and a constant therapeutic response. 76 parkinsonian patients were studied. Their L-dopa regimen was halved and 10 days after (-)deprenyl was added. After the decrease of L-dopa therapy a worsening of symptomatology was observed as expected. The association with (-)deprenyl was able to reverse this trend and when the inhibition of MAOB was really effective patients showed an improvement of symptoms even when compared to baseline values. No relevant side effects were observed and no patients dropped out.
Fluctuations in motor performances are the major problem in the longterm management of Parkinson's disease. In this study the clinical effects of L-dopa intravenous infusion were evaluated in 18 parkinsonian patients with fluctuations. 14 out of these were given Lisuride intravenous infusion in a following study. Lisuride is a potent dopamine agonist and it is highly soluble in water. The results obtained with L-dopa were very good and we found a close correlation between oral and intravenous dosage. The dosage of L-dopa infusion ranged between 360-1,250 mg for 12 hours. Lisuride proved to be able to give prolonged mobile state in 8 patients out of 14. The other 6 patients showed a different response to the drug. The dosage used ranged between 0.6 and 2.4 mg per day. No severe side-effects were observed during both studies except for nausea and vomiting occurring during Lisuride infusion.
In view of evidence linking cholecystokinin-containing neurons with both dopamine system function and Parkinson's disease pathophysiology, the therapeutic effects of the cholecystokinin analog, caerulein, were evaluated in 10 parkinsonian patients stabilized on L-Dopa therapy. Despite substantially elevated plasma caerulein levels immediately following intramuscular injection of this peptide, no consistent change in neurologic status could be discerned. These negative results may be due to the relatively small amounts of caerulein entering the CNS at dose levels that do not induce gastrointestinal toxicity.
The efficacies of an 2-agonist clonidine and an 2-antagonist mianserin were compared in two treatment groups, common migraine and tension headache sufferers. Forty patients entered this double-blind placebo-controlled study. Placebo, clonidine 0.150 mg, and mianserin 30 mg were each administered for 90 day periods. Headaches were induced by intravenous doses of histamine dihydrochloride. The histamine threshold in the common migraine group was significantly lower than in the tension headache group. In the common migraine group, mianserin decreased headache frequency. In the tension headache group, at 90 days mianserin significantly decreased headache intensity and headache frequency. Clonidine significantly decreased headache intensity at 90 days in the common migraine group. At 90 days, mianserin had significantly reduced the Hamilton Depression Rating Scale (HDRS) mean total score, (in the tension headache group), HDRS mean anxiety cluster scores (in both groups), and the HDRS mean depression cluster score (in the tension headache group). At 90 days, clonidine had significantly reduced the HDRS mean total score (in the tension headache group) and HDRS mean anxiety cluster scores (in both groups).
NMR has proved useful in the detection of Acute Cerebrovascular Disorders (ACVD), providing information related either to the tissue signal intensity and relaxation times, or to the morphological aspects of cerebral structures. Eighteen patients suffering from ischemic Acute Cerebrovascular Disorders were studied. A comparison between NMR imaging and CT scan was performed. Ischemic lesions, presence of edema, presence of reactive gliosis and anatomical vascular anomalies were found.
The ganglioside composition of the so-called substrate-attached material (SAM), which remains tightly bound to the tissue culture dish after cells are detached by chelating agents, was compared with the ganglioside composition of released cell bodies in the cultures of normal and various virally-transformed Balb/c 3T3 cells. Regardless of whether the cells were untransformed or transformed, the SAM of their cultures shows a ganglioside structure characterized by a prevalence of the higher homologs, mainly GD1a, over the simpler gangliosides, even when the level of higher homologs was reduced in the cell bodies of transformed cells. This result cannot be ascribed to the presence of plasmamembranes in the SAM as shown by ganglioside analysis of the plasmamembranes of some of the cells under study. Only in a highly metastatic transformed cell line did the SAM contain the same low GD1a level as found in the cell bodies.
Explore the source record for details and available documents.