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Biomedical subjects

R Zini

Publications and source records attributed to R Zini.

At least 73 records · Page 4Linked to original sources
PubMed1987

Binding parameters and microbiological activity of macrolides, lincosamides and streptogramins against Staphylococcus aureus.

Parameters of erythromycin binding to Staphylococcus aureus were measured in-vitro using an equilibrium method with [3H]erythromycin. The dissociation constant of the complex, erythromycin-S. aureus sensitive strain, was KD = 0.11 microM. The maximal binding, representing the density of binding sites was 14,847 molecules/cell. No binding was detectable on the constitutive resistant strain. Macrolides, streptogramins and lincosamides displaced bound [3H]erythromycin by a competitive process indicating that these compounds share common binding sites on the bacteria, i.e. 50 S ribosomal subunits. A good correlation (r = 0.99) was demonstrated between the corresponding inhibition constants (Ki) and the minimal inhibitory concentration. It is proposed that knowledge of the binding parameters provides a good indication of bacterial susceptibility and may serve as a useful adjunct in developing new compounds.

Anti-Bacterial Agents↗
PubMed1987

Alterations of beta-adrenergic, muscarinic cholinergic receptors and imipramine binding sites in human lung tumors.

Direct ligand binding techniques have been used to compare beta-adrenergic receptors, muscarinic cholinergic receptors and imipramine binding sites in human tumoral and healthy lungs removed from eleven patients during operations. Beta-adrenergic and muscarinic cholinergic receptors are present in tumoral tissues but their concentrations were decreased compared to healthy tissues. Imipramine binding sites were absent. It is concluded that this type of studies could bring additional information to morbid anatomy analysis and be used to follow illness evolution.

Adenocarcinoma↗
PubMed1986

In vitro [3H]-erythromycin binding to Staphylococcus aureus.

Characteristics of erythromycin binding to Staphylococcus aureus were determined by using kinetics and equilibrium binding experiments. Both methods yielded identical values of the dissociation constant, i.e. 0.1 muM. This value was in accord with that found with a bacterial extract of ribosomes which are the organelles where erythromycin exerts its action. This good agreement shows that the dissociation constant of erythromycin determined with intact bacteria is a good reflect of specific bacterial receptors of macrolides, i.e. ribosomes. In addition, mechanism of uptake of the antibiotic by Staphylococcus aureus was investigated. Passive diffusion process was shown to be mainly responsible for this phenomenon.

Erythromycin↗
PubMed1986

Inhibition of binedaline binding to human alpha 1-acid glycoprotein and other serum proteins by chlorpromazine, imipramine, and propranolol.

Binedaline (1-[[2-(dimethylamino)ethyl]methylamino]- 3-phenylindole) binding to human alpha 1-acid glycoprotein and other serum proteins was studied in the presence of three basic compounds: chlorpromazine, propranolol, and imipramine. In serum, at therapeutic concentrations, binedaline binding was not modified by the presence of these three compounds, nor did binedaline inhibit the binding of these compounds. With isolated alpha 1-acid glycoprotein, the four drugs exhibited competitive inhibition indicating that they share a common binding site on this protein.

Adult↗
PubMed1986

In vitro binding study of gemfibrozil to human serum proteins and erythrocytes: interactions with other drugs.

The binding of gemfibrozil to human serum, isolated proteins and erythrocytes was studied in vitro by equilibrium dialysis. Our results show that this drug is highly bound to serum (99%) at therapeutic levels. Human serum albumin was shown to be mainly responsible for this binding (98.6%) with a saturable process characterized by two binding sites with a moderate affinity. Like many acidic drugs with a carboxylic acidic group, gemfibrozil showed none or negligible binding to alpha 1 acid glycoprotein, lipoproteins and gamma-globulins. The drug binding to erythrocytes is very low (0.8%). The unbound fraction in blood remains constant (0.8%) within the range of therapeutic concentrations. Moreover, interactions were studied with bilirubin and palmitic acid at pathophysiological concentrations and acenocoumarol, salicylic acid, valproic acid, furosemide, phenylbutazone, tolbutamide, warfarin and sulfamethoxazol at therapeutic concentrations. Neither endogenous compounds nor the other drugs studied altered gemfibrozil binding in serum. Likewise, the binding of warfarin to serum and to human serum albumin (600 microM) is not influenced by gemfibrozil.

Blood Proteins↗
PubMed1985

Protein binding of propisomide.

This paper describes the protein binding of propisomide to human serum and isolated proteins using equilibrium dialysis. The drug is exclusively bound to alpha1-acid glycoprotein with high affinity. The binding is saturable even at low concentrations of the drug. Thus, the fraction unbound varied from 0.05 to 0.60 with decreasing serum concentration. The major metabolite of the drug or other drugs with affinity for alpha1-acid glycoprotein can displace propisomide from its binding site only when present in serum at high levels. Two ultrafiltration techniques are compared to equilibrium dialysis for the determination of serum protein binding of propisomide. Ultrafiltration does not give reliable results. Equilibrium dialysis is retained as an accurate method for the determination of the fraction unbound of propisomide.

Adult↗
PubMed1985

Binedaline binding to plasma proteins and red blood cells in humans.

Serum binding of binedaline, a new antidepressant drug, was studied in vitro by equilibrium dialysis. The percent of binding in serum is high, 99.2%, and remains constant within the range of therapeutic concentrations; no saturation to the binding sites was seen. Investigations performed on isolated proteins with a wide range of concentrations showed one site with a high affinity constant (Ka = 2 X 10(6) M-1) for alpha 1-acid glycoprotein and two sites with a low affinity constant (Ka = 3 X 10(4) M-1) for human serum albumin. Binding to lipoproteins was nonsaturable, with a total affinity constant of 1.25 X 10(5) less than nKa less than 2.79 X 10(6) M-1. Over the range of therapeutic concentrations, the ratio of binedaline concentrations in serum and red blood cells remained constant (1%) and was shown to be dependent on the free fraction of binedaline in serum.

Antidepressive Agents↗
PubMed1984

Evidence for high affinity [3H] imipramine binding sites in human lung.

[3H] imipramine exhibits both saturable and high affinity binding sites in human lung with a maximal number of binding sites of 7.50 pmoles/mg protein and a dissociation constant of 1.74 nM. Displacement studies indicate that these sites can be considered as specific of imipramine, tricyclic compounds and also monoamine uptake inhibitors:fluoxetine and nisoxetine. Atypical antidepressants were inactive as ligands of main known receptors.

Antidepressive Agents↗
PubMed1984

Plasma protein binding of metbufen, a new non-steroid anti-inflammatory drug, in humans.

The binding of 14C-metbufen to human serum albumin and to plasma of cirrhotic patients was measured by equilibrium dialysis at 37 degrees C, pH = 7.4. Between 0.37-373 microM, binding of metbufen to human serum is linear and 99% complete. HSA is the only binding protein with two classes of saturable binding sites. The binding parameters are n1 = 3-5; K1 = 40000 M-1; n2 = 5-8; K2 = 2000 M-1 and n1 = 2; K1 = 148000 M-1, n2 = 7.5; K2 = 2800 M-1 to serum (600 microM HSA) and HSA (600 microM), respectively. The higher affinity constants of pure commercial HSA than found in serum and the lower number of binding sites are thought to be due to albumin polymerization in commercial HSA. In plasma from cirrhotic patients (total bilirubin: 232 microM; HSA = 450 microM), at 7.5 and 30 microM, metbufen-free fractions increased from 1.4 to 2.4% and 1.3 to 3.6%, respectively. At 2 or 8 micrograms/ml, metbufen is not displaced by salicylic acid (300 micrograms/ml), CPIB (200 micrograms/ml), furosemide (2 micrograms/ml), itanoxone (20 micrograms/ml), tolbutamide (100 micrograms/ml), warfarin (3 micrograms/ml), or diazepam (0.75 micrograms/ml). Finally, metbufen interacts with both the diazepam and warfarin binding sites of HSA to some degree.

Anti-Inflammatory Agents↗
PubMed1983

Binding of propranolol and iodocyanopindolol to isolated cells, homogenates and plasma membranes of rat liver, lung, kidney and heart.

3H-(+/-) propranolol and 125I-(+/-) cyanopindolol have been used to characterize beta adrenoceptors of liver, lung, kidney and heart of rat. Two main binding parameters, KD and Bmax were measured using either cells, homogenates or plasma membranes of each organ (except heart). Results show that the most accurate determination of KD and Bmax involves: (1) a previous extraction of plasma membranes (2) the use of a ligand of a high affinity for beta adrenoceptors (3) a high specific radioactivity of this ligand. 125I-(+/-) cyanopindolol seems to be a better ligand than 3H(+/-) propranolol for such determinations.

Animals↗
PubMed1983

Binding of clometacin to human serum albumin. Interactions with clofibrate, indomethacin, salicylic acid and warfarin.

The binding of clometacin to human serum albumin (HSA) was studied in vitro by equilibrium dialysis. Our results show that binding to HSA is 99% at therapeutic levels. Binding is characterized by several numbers of binding sites (n = 8) with a moderate association constant (K = 2.7 X 10(4) M-1) and by another non-saturable phenomenon (nK = 4200 M-1). Moreover, interactions were studied with many drugs. Clometacin binding was altered by indomethacin, warfarin, chlorophenoxyisobutyrate (CPIB) and salicylic acid (SA). Conversely, clometacin inhibited the binding of these drugs. Finally, all these results were compared with those previously obtained with indomethacin, a positional isomer of clometacin.

Analgesics↗
PubMed1983

Plasma protein binding of the reversible type A MAO inhibitor cimoxatone (MD 780515).

Binding of a new selective reversible type A MAO inhibitor cimoxatone (MD 780515) to plasma proteins was studied in vitro by equilibrium dialysis. Binding to 580 microM human serum albumin (HSA) and to total plasma proteins was 93-96% and independent of cimoxatone concentration (0.15-207 microM). The drug was mainly bound to HSA with two binding sites and a moderate association constant (K = 2.9 X 10(4) M-1). Free fatty acids did not modify cimoxatone binding to HSA. Cimoxatone was also moderately bound to isolated lipoprotein fractions; alpha 1-acid glycoprotein and gamma-globulins did not play an important role in the binding of cimoxatone. MD 770222, the O-demethyl metabolite, appeared to be bound to HSA at the same binding sites as cimoxatone. However, no interaction occurred between the two compounds for 580 microM HSA. L-Tryptophan, bilirubin, the benzodiazepines flunitrazepam and oxazepam, imipramine and aspirin, did not displace cimoxatone from its binding sites. On the other hand, warfarin and phenylbutazone decreased cimoxatone binding to 29 microM HSA but no interaction occurred with 580 microM HSA.

Bilirubin↗
PubMed1983

Plasma binding of an alpha-blocking agent, nicergoline--affinity for serum albumin and native and modified alpha 1-acid glycoprotein.

The binding of nicergoline, an alpha-blocking drug, by human plasma proteins was studied using gel filtration, polyacrylamide gel electrophoresis, and equilibrium dialysis techniques. 3H-labeled nicergoline added to plasma was eluted together with two major protein fractions, one containing mainly serum albumin, the other glycoproteins such as alpha 1-acid glycoprotein (alpha 1-AG). Equilibrium dialysis experiments with pure human serum albumin and alpha 1-AG as well as with its chemically modified forms, desialylated, carboxymethylated, and both desialylated and carboxymethylated alpha 1-AG gave the following results: nicergoline has about a 4-fold higher affinity for alpha 1-AG than for serum albumin. There are two binding sites per molecule on serum albumin and one on alpha 1-AG. The binding parameters of alpha 1-AG were not significantly modified by desialylation or carboxymethylation. Only desialylated and carboxymethylated alpha 1-AG showed a decreased binding for nicergoline, suggesting conformational modifications induced by these combined treatments. The fact that desialylated alpha 1-AG keeps its affinity for nicergoline suggests the possibility of a selective introduction of this drug in cells possessing the Ashwell-type specific receptor for desialylated alpha 1-AG, for instance hepatocytes. Increased serum alpha 1-AG concentration induced by inflammatory reactions will also modify the distribution of bound nicergoline between serum albumin and alpha 1-AG and as a consequence its half-life and cell distribution.

Binding Sites↗
PubMed1982

Evidence for binding of certain acidic drugs to alpha 1-acid glycoprotein.

The binding of some acidic drugs to alpha 1-AGP was studied by equilibrium dialysis at 37 degrees, pH 7.4. Certain acidic drugs bound to alpha 1-AGP at one binding site with a high affinity. Though the alpha 1-AGP plasma concentration is far lower than the HSA concentration, the association constants of some acidic drugs with alpha 1-AGP are high enough to suggest that binding to alpha 1-AGP will contribute significantly to the total plasma binding of these drugs.

Humans↗