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Biomedical subjects

P Nguyen

Publications and source records attributed to P Nguyen.

At least 163 records · Page 9Linked to original sources
PubMed1992

Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE.

The bindings of perindopril and of its active metabolite perindoprilat to human serum, isolated proteins and to erythrocytes were studied by equilibrium dialysis. Within the therapeutic concentrations range, perindopril was 74% bound to serum involving a non-saturable process, NKa = 2.87. The main binders are serum albumin and alpha 1-acid glycoprotein. The serum binding of perindoprilat involved two successive steps. First, a saturable high-affinity binding (Ka: 2.8 x 10(9) M-1) occurred, involving probably the angiotensin converting enzyme (ACE). The second binding step was non-saturable with a very weak binding capacity, NKa = 0.15, quite superimposable to the HSA bound perindoprilat. Free fatty acids (FFA) did not alter the binding to HSA. The binding of both compounds to erythrocytes was low especially with perindopril, when measured in the presence of plasma. A significant correlation showed that the overall serum binding percentage of both drugs was essentially determined by HSA concentration. Serum binding was decreased in renal failure or cirrhosis, this result was principally linked to the hypoalbuminemia. Interactions with other drugs were limited to the binding of salicylate, tolbutamide and digitoxin to HSA.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1991

Effects of 5-HT3 receptor antagonists on behavioural measures of naloxone-precipitated opioid withdrawal.

The effect of the selective 5-HT3 receptor antagonists, ondansetron and MDL 72,222, against various behaviours elicited by naloxone-precipitated morphine withdrawal were examined. Rats made dependent upon morphine by the subcutaneous implantation of a 75 mg pellet, when challenged with naloxone (0.5 mg/kg SC), 3 or 4 days later exhibited a wide range of behaviours including wet dog shakes, paw shakes, salivation and a marked weight loss. Pre-treatment with ondansetron (0.01-1 mg/kg SC) or MDL 72,222 (1-3 mg/kg SC) failed to affect the incidence of these responses except weight loss, which was attenuated by both treatments. At doses similar to and below those required to elicit the withdrawal syndrome, naloxone produced a single-trial place aversion in morphine dependent rats. The place aversion produced by naloxone (0.05 mg/kg SC) was antagonized by pre-treatment of ondansetron (0.1-1 mg/kg SC) and MDL 72,222 (1 mg/kg SC) prior to conditioning. Chlordiazepoxide (10 mg/kg IP) but not gepirone (3-10 mg/kg SC) was similarly effective. It is concluded that 5-HT3 antagonists may attenuate some but not all behavioural signs associated with morphine withdrawal. Reasons for this apparent selectivity are discussed.

Animals↗
PubMed1991

[Alterations in erythrocyte membrane. Effect of neutrophil activation].

White blood cells, especially polymorphonuclear neutrophils (PMN), are known to alter some hemorheological parameters. Most of in vitro results have been obtained with passive PMN. Stimulated PMN also lead to other hemorheological changes. In our study, we have firstly activated PMN with opsonized zymosan and collected a PMN-free supernatant after 30 minutes activation. This supernatant was secondarily incubated with erythrocytes either in whole blood or in suspension. After 10 minutes incubation, hemorheological parameters were evaluated: 1) red blood deformability (RBC) (Ektacytometer* Technicon), 2) RBC filtration (Hemorheometer MK 1), 3) RBC aggregation (Erythroaggregometer* Sefam), 4) Plasmatic and whole blood viscosities (Low Shear 30* Contraves). Our results show that activated PMN-supernatant increases rigidity index (IR) of RBC in suspensions (IR of RBC control = 14.59 +/- 3.30 towards RI of incubated RBC = 22.91 +/- 7.06 p less than 0.001). Other rheological parameters remain unchanged. Activated PMN suspenatant influence on RBC is slight but could suggest of an alteration of RBC membrane. With an in vitro model of washed platelets aggregation, we have previously demonstrated that proaggregant activity of PMN supernatant was inhibited by specific Platelet-Activating Factor (PAF-acether) antagonists: BN 52021, BN 50723, Web 2086. We have so compared both effects of activated PMN-supernatant and synthetic PAF-acether on RBC membrane fluidity. Membrane fluidity was studied by fluorescence polarization of 4 probes embedded at different deep in the membrane of intact RBC. Similar modifications of RBC membrane fluidity are observed with either synthetic PAF-acether or PMN supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Membrane↗
PubMed1991

[Effects of contrast media products on erythrocyte aggregation. An ex vivo study].

It has been suggested (Fisher and al., Rainiko and al.) that contrast media could interfere with a red blood cell aggregation, low-osmolarity and non ionic contrast media leading to red blood cell aggregates in vitro. Clinical significance of this phenomenon is not known. We have studied 21 consecutive patients admitted in X ray department for pyelography. Sodium and meglumine ioxitalamate (Telebrix 38 R; Guerbet) osmolarity 2 100 mOsm kg--viscosity 8.5 cp at 37 degrees C is used for contrast. Red blood cell aggregation is studied by erythraggregometer Sefam. Samples are collected before (T0), 10 and 30 minutes (T10, T30) after contrast infusion. Hemogram and coagulation parameters are measured in parallel. Results show a significant increase of aggregation times at T10, with a trend towards baseline at T30. Dissociation shear rates follow the same fluctuations. We note a concomitant diminution of both fibrinogen and hematocrit levels, well-correlated with red blood cell aggregation. These results suggest a process of hemodilution which could explain the diminution of red blood cell aggregation with this type of contrast medium.

Adult↗
PubMed1990

[Effect of contrast media products on the erythrocyte aggregation and deformability in vitro].

It has been suggested that contrast media could interfere with red blood cell aggregation, hyperosmolar media leading to an inhibition of red blood cell aggregation whereas non ionic products might induce a sludge phenomenon. We present an in vitro study accompanying two contrast media: 1) Ioxitalamate of sodium and meglumin (ionic, hyperosmolar). 2) Iopaminol (non ionic). In their effect on hemorheological parameters of red blood cell aggregation. Blood samples have been obtained from 7 healthy donors. Contrast media have been tested at increased contrast media (O.1, 1, 2, 10, 100 mg/ml of Iodine in final concentration). The following parameters have been studied: hematocrit, fibrinogen level, erythrocyte aggregation using the Erythro-aggregometer*, whole blood viscosity at 3 different shear rates (0.87, 18.74, 118 sec.-1) using Low Shear 30*. Deformability of red blood cell was assessed by ektacytometry. Osmolarity was controlled in each sample. Results show an inhibition effect of both contrasts media on red blood cell aggregation. There is a concomitant decrease of blood viscosity at low shear rates. On the contrary, apparent viscosity increases at high shear rates in parallel with the contrast media concentration. This effect is more pronounced with ioxitalamate above a concentration of 10 mg/ml. Ektacytometric parameters are not modified by contrast media and this could indicate a complete reversibility of the media-induced alteration on red blood cell. In order to precise the prothrombotic effect on contrast media, hemorheological studies have to be completed by the assessment of their effect on hemostatic parameters.

Adult↗
PubMed1989

Evidence for isoxicam binding to site I as a primary site and to site II as a secondary site of human serum albumin.

Isoxicam binding to HSA was studied using equilibrium dialysis and fluorescence methods. It was shown that this drug binds to or near site I (warfarin or azapropazone site) and to site II (the diazepam site) as a secondary site, although it is generally considered that their respective drug structural requirements are often exclusive. The binding parameters were calculated with different mathematical models; a site oriented model with or without fixing the number of binding sites as integer values and a stoichiometric model. The relevant results are in good agreement under the selected experimental conditions. The stoichiometric method indicates that no positive cooperativity occurred during the binding process but other interactions between the two sites cannot be excluded.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Blood distribution of tenoxicam in humans: a particular HSA drug interaction.

Blood binding of tenoxicam was studied in vitro by equilibrium dialysis. Isolated human plasma proteins and blood cells were checked, and the distribution of the bound form was then calculated. The results showed that tenoxicam is mainly bound to HSA and that binding percentages are not different when measured in plasma (98.4%) and in an HSA solution at physiological concentration (704 microM, 98.15%). In these conditions, within the range of 1-150 microM, the tenoxicam binding percentage remained constant, evidence of a nonsaturable process. When a lower HSA concentration (10 microM) was used, the binding parameters of the tenoxicam interaction were calculated by using the same equilibrium dialysis data, by 3 methods of analysis- a stoichiometric method and site-oriented methods, fixing or not the number of HSA binding sites (n) as integer values. The best fit was observed with the first method, suggesting that two main interactions occurred. The site-oriented method gave lesser fits, the better being observed when n was not fixed. Its value, 1.77, suggest the possibility of two binding sites, one of them not preformed. The effects of known markers of site I, warfarin and apazone, of site II, diazepam and ibuprofen and of palmitic acid showed that tenoxicam is bound simultaneously to both sites I and II. The binding capacity of site I for tenoxicam is enhanced by diazepam: as this compound alone is bound to site II, this result suggests that the two HSA binding sites are not independent.

Bilirubin↗
PubMed1989

Prolonged exposure of neutrophils to saline or bronchoalveolar lavage fluid does not alter superoxide anion generation.

The role played by neutrophils (PMNs) in the genesis of lung injury in diverse clinical situations, such as bronchial asthma, idiopathic pulmonary fibrosis, and the adult respiratory distress syndrome, is an area of intensive investigation. Functional studies of PMNs, particularly those obtained from the alveoli by bronchoalveolar lavage, should shed light on their contribution to lung injury. However, it has not been demonstrated whether procedures used to harvest cells from the lung (bronchoalveolar lavage), particularly the potentially prolonged exposure to saline, commonly used to perform lavage, and other components of lavage fluid, can alter the functional characteristics of PMNs. In this report we demonstrate that a 2- to 3-hour exposure of neutrophils to saline from both humans and sheep in vitro does not alter the functional characteristics of PMNs as determined by superoxide anion generation after activation with phorbol myristate acetate (PMA; 6.96 +/- 0.44 vs. 7.60 +/- 0.32 nmol O2-/250,000 PMNs for control and saline-treated human cells, respectively, after a 45-min incubation with 10(-7) M PMA, and 4.73 +/- 0.30 vs. 4.50 +/- 0.42 nmol O2-/250,000 PMNs for control and saline-treated sheep cells). In a second series of experiments, we studied the effect of exposure of human PMNs to bronchoalveolar lavage fluid supernatants obtained from normal volunteers on superoxide anion generation by neutrophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Assays of apolipoproteins A and B as atherogenicity factors in aged patients at hospitals].

A systematic study of 100 elderly patients in a hospital geriatric unit was undertaken to analyse the relationship between clinical cardiovascular events (angina, myocardial infarction, hypertension, cerebrovascular accidents, temporo-spatial disorientation, invalidity, incontinence) and plasma lipids (total cholesterol, HDL and LDL fractions, triglycerides, apolipoprotein A and B and total cholesterol/HDL and apolipoprotein B/A ratios). The average triglyceride and apolipoprotein A concentrations were related to the patient's validity: The triglycerides were significantly higher in the group of invalid patients (+22%), p = 0.05. The apolipoprotein A levels were significantly lower in the invalid group (-12%), p = 0.05.

Aged↗
PubMed1989

[Aldehydes and ketones in silage: quantitative analysis by high performance liquid chromatography].

Carbonyl compound toxicity is known in several species but no study has been carried out with ruminants. Such volatile compounds exist in silages. After condensation of aldehydes and ketones with 2,4-dinitrophenylhydrazine, quantitative analysis was performed with 37 silages. It was found that quantities of carbonyl compounds varied from 36 mg/kg of dry matter (DM) to 1,535 mg/kg DM with a mean value of 642 mg/kg DM. Ethanal was 63% of the total amount of carbonyl compounds (mol/kg DM). Other molecules were propanal, propanone, butanal (n- and iso-), butanone and n- and iso- pentanal. The total amount of carbonyl compounds correlated positively with the dry matter percentage and negatively with the pH, crude fiber, ash content and volatile fatty acids. Thus, carbonyl compounds seem to be dependent up on silage storage conditions. Lactic flora could be involved in the synthesis of these compounds.

Aldehydes↗
PubMed1987

Intrathecal diazepam suppresses nociceptive reflexes and potentiates electroacupuncture effects in pentobarbital-anesthetized rats.

Using noxious heat-evoked tail flick in rats anesthetized with pentobarbital infusion, we studied the effects of diazepam applied intrathecally. This drug caused a marked suppression of nociceptive reflexes in a dose-dependent manner. In addition, a small non-suppressive dose of diazepam potentiated electroacupuncture effects. These results are discussed in terms of gamma-aminobutyric acid (GABA) since it is known that diazepam enhances binding of GABA to its receptor and hence potentiates inhibitory effects of GABA in the spinal cord. The possible synergism of diazepam and pentobarbital is also discussed.

Acupuncture Therapy↗
PubMed1987

Reduction of enucleation-induced metastasis in intraocular melanoma by periorbital irradiation.

The optimum treatment of malignant choroidal melanoma remains controversial. Some authors have hypothesized that enucleation promotes metastatic disease. This hypothesis has been demonstrated in the B16F10 melanoma mouse model. The present study used this model to examine the effect of external beam irradiation as a means of reducing metastases induced by enucleation. The results show a dose-dependent reduction in the DNA synthesis of irradiated melanoma cells. Administration of 800 cGy (800 rad) of radiation produced a 90% reduction in DNA synthesis; however, higher levels of radiation failed to produce further depression of cell proliferation. Irradiation of melanoma cells before intravenous injection resulted in a significant dose-dependent reduction in the number of lung metastases. While there was no effect with 100 cGy (100 rad) of radiation, 1000 cGy (1000 rad) produced a 95% reduction in metastases. In the animal model of enucleation-induced metastasis, 2000 cGy (2000 rad) delivered to the orbit either before or after enucleation produced a significant reduction in the number of lung tumors, compared with animals that did not undergo irradiation; 1000 cGy (1000 rad) delivered before enucleation did not have such an effect. These studies provide evidence that periorbital external beam irradiation is useful in reducing metastases following enucleation of a malignant melanoma in this animal model.

Animals↗
PubMed1987

Binding of 8-methoxypsoralen to human serum proteins and red blood cells.

Serum binding of 8-methoxypsoralen (8-MOP) was studied by equilibrium dialysis. In therapeutic concentrations, 8-MOP binding in serum was high, 91.4%, and constant, indicating concentration-independent kinetics. This binding involved the two main proteins, human serum albumin and alpha 1-acid glycoprotein, in a saturable process with one class of binding sites (n) and affinity constants (Ka) of 1.295 X 10(4) mol/l and 2.115 X 10(4) mol/l, respectively. Binding to lipoproteins and gamma globulins was negligible and non-saturable in therapeutic concentrations, with nKa values of 0.35, 0.024, 0.013 and 0.0004 mumol/l for VLDL, LDL, HDL and gamma globulins, respectively. Inhibition of 8-MOP serum binding was observed with salicylic acid and indomethacin, but not with diazepam, warfarin or erythromycin. Over a range of therapeutic concentrations, the ration of 8-MOP concentration in red blood cells (RBCs) and in serum was constant at 20.3% and three times higher than would be expected if a simple diffusion of the 8-MOP plasma free fraction (fu) occurred. According to the measured and calculated parameters, simulations of 8-MOP blood binding in pathological states (hypoalbuminaemia with or without inflammation) showed variations of fu which were partially 'buffered' by RBCs. Simulation of 8-MOP protein binding at cutaneous interstitial fluid level showed that fu is approximately 30% and permitted prediction of a decrease of fu available to the epidermis in case of local or systemic inflammation. This may imply an increase in the minimum phototoxic dose relevant for PUVA and explain some cases of 'poor' responsiveness of psoriatic patients to PUVA therapy.

Binding Sites↗
PubMed1986

Management of anti-thrombin III deficiency during pregnancy without administration of anti-thrombin III.

We report a patient with hereditary antithrombin III deficiency who was successfully treated with heparin throughout pregnancy. Functional antithrombin III levels fell to 0.32 U/ml during heparin treatment, but it was possible to achieve a heparin effect, measured by the activated partial thromboplastin time, thrombin clotting time and heparin assay with subcutaneous heparin in doses of 30,000 U to 35,000 U/24 hours. This achieve an long term heparin effect was obtained without the need for antithrombin III infusions.

Adolescent↗