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Biomedical subjects

M Nardini

Publications and source records attributed to M Nardini.

At least 55 records · Page 3Linked to original sources

Hemodynamic effects of transdermal nitroglycerin in subjects with angina and without congestive heart failure: comparison between never treated and chronically treated subjects.

Two groups of patients with angina were studied: Group A, 9 patients not treated previously with nitroderivatives; Group B, 8 patients, treated with transdermally administered nitroderivatives for at least 4 weeks. Hemodynamic parameters did not differ significantly in these groups under baseline conditions; only systolic blood pressure was higher in Group B (165 +/- 16 mmHg) than in Group A (144 +/- 15 mmHg). Hemodynamic modifications produced by administering nitroglycerin transdermally in these patient groups were evaluated 100 min after the transdermal application. In Group A significant reduction of systolic (144 +/- 15 to 126 +/- 18 mmHg, p less than 0.01) and diastolic blood pressure (83.36 +/- 70.1 +/- 13 mmHg, p less than 0.05), mean right atrial pressure (4.8 +/- 2.1 to 3 +/- 1.7 mmHg, p less than 0.005), mean pulmonary arterial pressure (18.6 +/- 2.6 to 16.7 +/- 2.8 mmHg, p less than 0.01), and significant increase of heart rate (72 +/- 10 to 83.5 +/- 12.4 beats/min, p less than 0.005) were noted. In Group B we noted only a significant reduction in systolic (170 +/- 25 to 150.5 +/- 16 mmHg, p less than 0.05) and diastolic blood pressure (88.7 +/- 15.5 to 77.5 +/- 9.2 mmHg, p less than 0.05) without other modifications. We conclude that prolonged treatment with adequate doses of transdermal nitroglycerin causes the hemodynamic effects of the medication to dissipate from the venous tone and significant arteriodilative effect to persist.

Administration, Cutaneous↗

Ketimine rings: useful detectors of enzymatic activities in solution and on polyacrylamide gel. Detection of L-amino acid oxidase, glutamine transaminase, pantetheinase, and acylase I.

A simple procedure has been developed for the detection of L-amino acid oxidase, glutamine transaminase, pantetheinase, and acylase I in solution and on polyacrylamide gels. The method is based on the strong absorbance at 296 nm of some ketimine rings which can be directly produced by the enzymatic reaction or formed by the reaction of the enzymatic product with 3-bromopyruvate. The procedure allows one to visualize up to about 1-10 mU of enzyme.

Amidohydrolases↗

Italian multicenter study of reversible cerebral ischemic attacks. Part 5. Risk factors and cerebral atherosclerosis.

As part of a prospective study, the influence of several premorbid and environmental factors on the presence, extent and severity of cerebral vessel atherosclerosis was studied in 462 patients with clinical diagnosis of RIA who underwent cerebral angiography. The extent and severity of atherosclerosis of the cerebral vessels was quantified using extracranial and intracranial cerebrovascular scores (ECS, ICS) based on the number and severity of the lesions in 11 extracranial and 21 intracranial arterial segments. Results of univariate and multivariate analyses indicate that the presence of atherosclerotic changes of cerebral vessels, as shown by angiography, was strongly related with age in both sexes. The lesions were more frequent in males, in particular under age 55. Elevated cholesterol was associated with a higher incidence of atherosclerotic lesions. Smoking was associated with a higher incidence of extracranial lesions. Age, smoking and history of hypertension were the best predictors of the extent and severity of cerebral vessel atherosclerosis.

Adult↗

Hexahydro-1,4-thiazepine-3,5-dicarboxylic acid and thiomorpholine-3,5-dicarboxylic acid are present in normal human urine.

Hexahydro-1,4-thiazepine-3,5-dicarboxylic acid and thiomorpholine-3,5-dicarboxylic acid, simply referred to as cyclothionine and TMDA, respectively, are two cyclic sulfur-containing imino acids detected in bovine brain. Human urine has been investigated to establish the occurrence of these imino acids as common constituents under normal conditions. The morning urine of healthy subjects has been analyzed for enrichment of these compounds by using an ion-exchange procedure. Gas/liquid chromatography of the final extracts revealed the presence of peaks coeluting with authentic cyclothionine and TMDA. The latter compound eluted very close to an unknown sulfur-containing compound. A resolved peak of TMDA has been obtained by high-performance liquid chromatography of the final extracts derivatized with phenylisothiocyanate. Selected ion monitoring with multiple-ion detection applied to the compounds separated by gas chromatography revealed the presence of the respective molecular ions and of the decarboxylated fragments, thus confirming the identification of cyclothionine and TMDA in human urine.

Adult↗

Cysteamine oxygenase: possible involvement of superoxide ion in the catalytic mechanism.

The reaction catalyzed by cysteamine oxygenase on cysteamine in the presence of phenazine methosulphate as cofactor like compound is inhibited by nitroblue tetrazolium, a scavenger of superoxide ions. The reaction is not inhibited by superoxide dismutase and allyl alcohol and it is not activated by superoxide ions produced in solution. Nitroblue tetrazolium is reduced by cysteamine or mercaptoethanol and phenazine methosulphate. This reaction is completely inhibited by superoxide dismutase. In the presence of cysteamine oxygenase the reduction with mercaptoethanol is greatly enhanced and it is only partially inhibited by superoxide dismutase. According to these data a reaction mechanism is proposed in which superoxide ions and thiyl radicals are produced at the active site during catalysis.

1-Propanol↗

The transamination of L-cystathionine, L-cystine and related compounds by a bovine kidney transaminase.

An enzyme which actively transaminates L-cystathionine, L-cystine, L-lanthionine and S-aminoethyl-L-cysteine has been purified from bovine kidney. The transaminase appears to be pure up to 90% and probably consists of two subunits of similar molecular mass of about 47 kDa. The enzymatic products arising from the transamination of L-cystathionine and related compounds spontaneously cyclize into ketiminic structures, which are the immediate precursors of unusual imino acids recovered in biological materials. The specificity towards other amino acid and oxo acid acceptors is similar to the specificity exhibited by rat kidney glutamine transaminase. This suggests that the sulfur amino acid transaminations that have been described could be performed by the bovine kidney glutamine transaminase.

Alanine↗

Interaction of pantetheinase with sulfhydryl reagents and disulfides.

The effect of many thiol reagents and disulfides on pantetheinase (E.C. 3.5.1.-; pantetheine hydrolase) was studied in the presence or absence of S-pantetheine-3-pyruvate as substrate. Iodoacetamide, iodoacetate, bromopyruvate and N-ethylmaleimide irreversibly inactivate the enzyme at very different rates. Inactivation constants, corrected for the different reactivity of halogeno derivatives with non-protein thiols, suggest the presence of an essential sulfhydryl group in the enzyme and a negatively charged environment near this group. p-Chloromercuribenzoate is the most effective inhibitor; 2-nitro-5-thiocyanobenzoate, o-iodosobenzoate and hydrogen peroxide give a biphasic inhibition pattern, indicating the existence of two sulfhydryl groups whose modification affects activity. Organic arsenicals decrease activity to about 50%. Neutral and positively charged disulfides are effective inhibitors. Substrate protects the enzyme from inactivation, except in the case of negatively charged disulfides, where the presence of substrate enhances the inhibitory effect. Titration with Ellman's reagent or 4,4'-dithiodipyridine under various experimental conditions demonstrated the existence of two sulfhydryls and three disulfides in the fully active enzyme. Pantetheinase may become inactive during purification with concomitant loss of one titrable sulfhydryl group.

Alkylating Agents↗

[Fibrinolytic therapy in acute myocardial infarction. Coronarographic evaluation of short-term results].

The authors report their experience in fibrinolytic therapy with Urokinase in acute myocardial infarction. There were 3 groups of treatment: 100 patients with intracoronary fibrinolytic therapy; 77 patients with peripheral venous fibrinolytic administration; 31 patients with conventional therapy. The 3 groups underwent, between 21 and 28 days after the acute event, a coronarographic examination to evaluate the persistence of patency of the vessels involved in the myocardial infarction. The short term results show that the fibrinolytic therapy (with the limitations due to the hemorrhagic complications associated with the use of Urokinase), especially via intracoronary, is significantly more useful and reliable than conventional therapy, which appears unsatisfactory. Therapeutic failures are probably due to diffuse atherosclerosis of the vessel and/or to the old age of the thrombus.

Angiography↗

[Effects of reduction of blood viscosity at constant hematocrit on the cerebral blood flow].

It is well established that cerebral blood flow (CBF) is low in patients with high hematocrit and is high in anemic patients. An inverse relationship between CBF and hematocrit has been found. Furthermore, if hematocrit is reduced, CBF increases. There is some debate as to whether these observations are due to viscosity or to oxygen carrying capacity of the blood. In order to further elucidate this problem, CBF, blood viscosity and hematocrit were measured in 4 patients with paraproteinemias before and after paraproteins had been removed by plasmapheresis without changes in hematocrit. After plasmapheresis, blood viscosity significantly decreases and CBF increases by a mean of 24.4 ml/100 g/min. Mean arterial blood pressure and hematocrit were not influenced by plasmapheresis. These results indicate that blood viscosity is an important factor in determining CBF. This does not exclude the role of oxygen transport as an associated factor, but it is evident that oxygen transport and blood viscosity are independent variables in the control of CBF.

Blood Viscosity↗

Enzymatic production of S-(2-hydroxy-2-carboxyethyl)homocysteine.

The monodeamination product of L-cystathionine, S-(2-oxo-2-carboxyethyl)homocysteine is enzymatically reduced by human and hog L-lactate dehydrogenase to S-(2 hydroxy-2-carboxyhethyl)homocysteine which has been found in the urine of cystathioninuric patients. Km values are 6.6 mM and 13 mM for human and hog enzymes respectively. The reaction is not complete at alkaline pH values because of cyclization of the ketoacid into a 1,4 thiazepine derivative ring. By a coupled enzymatic system of L-amino acid oxidase and L-lactate dehydrogenase S-(2-hydroxy-2-carboxyethyl)homocysteine is also formed from L-cystathionine.

Animals↗

[A microanalytical gas liquid chromatography method with a nitrogen-phosphorus detector in the assay of various psychotropic drugs of tricyclic structure and of their N-demethylated metabolites].

Nanogram amounts of chlorimipramine, chlorpromazine and their Nor1- and Nor2-metabolites were detected in plasma by GLC with nitrogen-sensitive detection. Two extraction procedures were compared. The use of Sep Pak C18 cartridges produced a higher degree of accuracy and precision with significant time and materials saving, as compared to the use of organic solvents in a three steps extraction procedure.

Chlorpromazine↗

Continuous spectrophotometric assay of pantetheinase activity.

A continuous spectrophotometric assay for pantetheinase determination using S-pantetheine-3-pyruvate as substrate is described. The enzymatic hydrolysis of this new substrate leads to the formation of S-cysteamine-3-pyruvate, which cyclizes in a non-rate-limiting step to give 2H-1,4-thiazin-5,6-dihydro-3-carboxylic acid (aminoethylcysteine ketimine), a compound exhibiting a strong absorption at 296 nm. The assay is optimized with respect to pH, buffer, and substrate concentration. Prereduction of the enzyme and some properties of the reaction are also studied. The assay is simple, rapid, very sensitive, and specific.

Amidohydrolases↗

Interaction between 1,4-thiazine derivatives and D-amino-acid oxidase.

Aminoethylcysteine-ketimine (2H-1,4-thiazine-5,6-dihydro-3-carboxylic acid) strongly inhibits D-amino-acid oxidase (D-amino-acid:oxygen oxidoreductase (deaminating), EC 1.4.3.3). The inhibition is purely competitive (Ki = 3.3 X 10(-7) M). Aminoethylcysteine-ketimine modifies the visible spectrum of the enzyme: the absorption maxima of bound FAD shift from 375-455 nm to 385-445 nm with a definite shoulder at 465 nm; the appearance of a large absorption band centered at 750 nm may be due to a charge-transfer complex formation. The dissociation constant for the aminoethylcysteine-ketimine-enzyme complex, calculated by a photometric procedure (4 X 10(-7) M), is in good agreement with kinetic data. The dicarboxylic analogue of this inhibitor (lanthionine-ketimine) is ineffective in D-amino-acid oxidase inhibition and does not produce any spectral modification of the enzyme. These results confirm structural requirements for D-amino-acid oxidase inhibitor reported by other researchers. Ketimine reduced forms (thiomorpholine-2-carboxylic acid and thiomorpholine-2,6-dicarboxylic acid) are chemically synthesized and checked as D-amino-acid oxidase substrates: only thiomorpholine-2-carboxylic acid is oxidized to aminoethylcysteine-ketimine (Km = 2 X 10(-4) M).

Amino Acids, Sulfur↗

Similarity of the oxidation products of L-cystathionine by L-amino acid oxidase to those excreted by cystathioninuric patients.

L-Cystathionine is oxidized by snake venom L-amino acid oxidase at a rate about half that with L-leucine at pH 8.5. The appearance of an absorbance at 296 nm and quantitation of the products of oxidation in the presence of catalase indicate formation in the solutions of a seven-membered ketimine ring produced by cyclization of the monoamino monoketo derivative of cystathionine. A limited double deamination has also been observed. In the absence of catalase, S-(carboxymethyl)homocysteine and S-(beta-carboxyethyl)cysteine have been identified together with ninhydrin-unreactive compounds yielding the above mentioned carboxy compounds upon hydrolysis with HCl. Authentic samples of the monoamino monoketo analogs of cystathionine have been prepared and compared with the enzymatic products. Cyclization of the synthetic products into the ketimine ring is pH-dependent as established by UV spectrum and other assays. Compounds derived from either the oxidation or the reduction of the ketimine have been prepared. It was found that many products of enzymatic and chemical changes of cystathionine and its ketimine described in the present paper are identical with those identified in the urine of cystathioninuric patients. This result indicates the occurrence in humans of secondary metabolic routes of cystathionine centered on the production of cystathionine ketimine, in equilibrium with the open form, which in cystathioninurics is revealed by the lack of cystathionase.

Amino Acid Metabolism, Inborn Errors↗

Creutzfeld-Jakob disease in the province of Siena: two cases transmitted to monkeys.

Two cases of histopathologically documented Creutzfeldt-Jakob disease were observed in the same area of the province of Siena in 1974-1975. The transmission of the disease was obtained through brain homogenates and lymphnodes in one of the two cases. This confirms that the agent is present in other tissues besides the brain and underlines further the analogies between Creutzfeld-Jakob disease and scrapie.

Aged↗

Italian study of cerebral reversible ischemic attacks. II. The hematocrit and hemoglobin distribution and its relationship between clinical pattern and angiographic abnormalities.

A clinical and angiographic study was conducted in 360 patients with previous reversible ischemic attacks (RIAs) in order to verify the influence of hematocrit, hemoglobin and red cell count within the normal range in the clinical picture of cerebral infarction and its relationship with angiographic atherosclerosis. No significantly different distribution of the three parameters considered has been found according to the presence and the degree of atherosclerosis. On the contrary, our data have shown a significant correlation between levels of hematocrit, hemoglobin and red cell count and some clinical aspects of the RIA when angiographic atherosclerosis is present.

Adult↗