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Biomedical subjects

C Salerno

Publications and source records attributed to C Salerno.

At least 37 records · Page 2Linked to original sources
PubMed1997

Failure of muscle energy metabolism in a patient with adenylosuccinate lyase deficiency. An in vivo study by phosphorus NMR spectroscopy.

31P-nuclear magnetic resonance spectroscopy was used to investigate in vivo the energy metabolism of the calf muscle in a 10-year-old patient with adenylosuccinate lyase deficiency and severe psychomotor retardation. The patient showed a markedly reduced PCr/P(i) molar ratio, known to well represent the cytosolic phosphorylation potential, due to low PCr and high P(i) content in resting muscle. Moreover, intracellular ATP concentration was significantly lower than in the control group both at rest and at the end of post-exercise recovery. The rate of patient's PCr recovery after an exercise in ischaemic conditions was also out of the reference range, suggesting a reduced ability of mitochondria to respond to metabolic needs.

Adenosine Triphosphate↗
PubMed1997

The interaction of a new anti-tumour drug, KAR-2 with calmodulin.

1. KAR-2 (3"-(beta-chloroethyl)-2",4"-dioxo-3,5" -spiro-oxazolidino-4-deacetoxy-vinblastine) is a semisynthetic bis-indol derivative, with high anti-microtubular and anti-tumour activities but with low toxicity. KAR-2, in contrast to other biologically active bis-indols (e.g. vinblastine) did not show anti-calmodulin activity in vitro (enzyme kinetic, fluorescence anisotropy and immunological tests). 2. Direct binding studies (fluorescence resonance energy transfer, circular dichroism) provided evidence for the binding of KAR-2 to calmodulin. The binding affinity of KAR-2 to calmodulin (dissociation constant was about 5 microM) in the presence of Ca2+ was comparable to that of vinblastine. 3. KAR-2 was able to interact with apo-calmodulin as well; in the absence of Ca2+ the binding was of cooperative nature. 4. The effect of drugs on Ca2+ homeostasis in human neutrophil cells was investigated by means of a specific fluorescent probe. Trifluoperazine extensively inhibited the elevation of intracellular Ca2+ level, vinblastine did not appreciably affect it, KAR-2 stimulated the Ca2+ influx and after a transient enhancement the Ca2+ concentration reached a new steady-state level. 5. Comparison of the data obtained with KAR-2 and bis-indols used in chemotherapy suggests that the lack of anti-calmodulin potency resides on the spiro-oxazolidino portion of KAR-2. This character of KAR-2 manifested itself in various systems and might result in its low in vivo toxicity, established in an anti-tumour test.

Animals↗
PubMed1997

Inhibition of NADPH oxidase-mediated superoxide radical formation in PMA-stimulated human neutrophils by 4-hydroxynonenal--binding to -SH and -NH2 groups.

4-Hydroxynonenal (HNE), a major lipid peroxidation product, effectively inhibits the superoxide radical formation by NADPH oxidase of phorbol myristate acetate (PMA)--stimulated human PMNL. The I50 value for the inhibition of NADPH oxidase-mediated superoxide radical formation by 4-hydroxynonenal was found to be 19 microM. The HNE inhibition involves the reaction with both -SH and -NH2 groups. Superoxide formation as final result of the NADPH oxidase cascade was almost completely restored by addition of dithiothreitol. In presence of hydroxylamine only a minor restoration of superoxide radical formation was found. A combination of dithiothreitol and hydroxylamine yielded the greatest recovery. Two other aldehydes with the same chain length as HNE but different binding to lysine, histidine and cysteine residues, trans-2,3-nonenal and nonanal, gave I50 values for the inhibition of NADPH oxidase-mediated superoxide formation rate of 110 microM or > 300 microM, respectively.

Aldehydes↗
PubMed1995

Adenylosuccinase deficiency: a patient with impaired erythrocyte activity and anomalous response to intravenous fructose.

Clinical and biochemical data are presented on an Italian patient with adenylosuccinase deficiency of both erythrocytes and mixed peripheral blood lymphocytes. The erythrocyte enzyme showed normal substrate affinity, but decreased thermal stability. The patient displayed an anomalous response to an intravenous fructose tolerance test with a rise in plasma [Mg2+] and [K+] and a drop in plasma levels of inorganic phosphate, glucose, urate and succinylnucleosides upon fructose injection.

Adenylosuccinate Lyase↗
PubMed1993

Polyene antibiotics inhibit superoxide-producing NADPH oxidase in a polymorphonuclear cell-free system.

We studied the effect of polyene macrolide antibiotics on the NADPH-dependent superoxide production induced by arachidonic acid in a cell-free system consisting of the membrane and cytosolic fractions obtained from bovine polymorphonuclear leukocytes. Preincubation of the membrane fraction with polyenes before addition of the soluble components of the reaction mixture resulted in a dose-dependent inhibition of superoxide production.

Animals↗
PubMed1993

Adenosine affects the f-met-leu-phe induced changes in cytosolic Ca2+ and in membrane potential of human granulocytes.

Indo 1 acetoxymethyl ester and 3,3-dipentyloxacarbocyanine iodide have been used to investigate the effect of adenosine on the changes in cytosolic Ca2+ concentration and in membrane potential of human granulocytes activated by the chemotactic tripeptide f-met-leu-phe. Adenosine does not significantly affect negative (hyperpolarizing) potential changes as well as calcium accumulation in cytosol, whereas both the amplitude of the depolarization phase and the relaxation time for restoring the initial intracellular calcium level are reduced.

Adenosine↗
PubMed1993

Angiotensin-converting enzyme activator from purified human neutrophils.

An endogenous ACE activator has been revealed. Neutrophil-enriched human leucocyte preparations released in isotonic media a relatively thermostable factor, capable of increasing the angiotensin-converting enzyme activity 1.6-2.0-fold. Activator would not pass through a 30 kDa cutoff membrane. Data on the presence of the activator in vivo were obtained in studies of protein-free serum fractions of patients with a hereditary CI-esterase inhibitor deficiency. It was suggested that the neutrophil-released ACE activator could have a role in the modulation of the inflammatory response.

Adult↗
PubMed1992

Pulmonary resection for metastatic breast cancer.

Thirty-three patients treated primarily with surgical excision of pulmonary metastases from breast cancer were compared with 30 patients treated primarily with systemic chemohormonal therapy. Treatment for patients in the surgical group included pulmonary resection alone in 20, resection plus adjuvant systemic therapy in nine, and resection plus adjuvant radiation therapy in four. Treatment for patients in the medical group included systemic therapy alone in 22 and systemic therapy plus local radiation therapy in eight. Mean survival in the surgical group was significantly longer than that in the medical group, even when only those patients who manifested single pulmonary nodules were compared (58 months vs 34 months). The overall 5-year survival rate after treatment of lung metastasis was significantly greater for the surgical group than for the medical group (36% vs 11%). The results of this study indicate that surgical resection should be considered in patients with breast cancer who develop operable pulmonary metastases without evidence for concomitant extrapulmonary disease. In selected patients, such therapy may result in a survival benefit.

Academic Medical Centers↗
PubMed1992

Effect of inorganic phosphate on hypoxanthine transport in isolated brain microvessels.

In isolated brain microvessels, used as an in vitro model of the blood-brain barrier, the rate of hypoxanthine uptake was modulated by the presence of inorganic phosphate. A single high-capacity, low-affinity transport system was apparently active in a phosphate-free medium (Vmax = 840 pmol/mg protein/min, Km = 750/uM); in the presence of 10 mM phosphate, there was also a low-capacity, high-affinity system (Vmax = 47 pmol/mg protein/min, Km = 27/uM). The phosphate-dependent component was inactive in the absence of glucose or of Na+ ions, or upon addition of phloretine (but was scarcely affected by 2,4-dinitrophenol). This activity was apparently coupled to the intracellular phosphoribosyltransferase-catalyzed conversion of purines into the corresponding nucleotides: when inorganic phosphate was present in the suspending medium, labeled hypoxanthine was transported with higher efficiency and was readily converted to inosine monophosphate and to other related nucleotides. In the absence of phosphate ions, hypoxanthine was instead metabolized to xanthine and uric acid.

Alkaline Phosphatase↗