PubMed Health⌕ Search

Biomedical subjects

F Boucher

Publications and source records attributed to F Boucher.

At least 55 records · Page 3Linked to original sources
PubMed1994

Intervention in ischaemia. Reperfusion syndrome. Rationale for trimetazidine.

Although early reperfusion of cardiac tissue is now considered to be the only intervention capable of restoring the various cellular functions altered by ischaemia and preventing progression towards necrosis of myocardial cells, reperfusion is frequently accompanied by various manifestations grouped under the heading of reperfusion syndrome or reperfusion injury. Functional recovery is therefore not immediate, but usually appears after a certain delay following a period of contractile dysfunction (myocardial stunning) lasting for several hours or even days after the start of reperfusion. Characteristics reperfusion-induced arrhythmias are also observed. The cellular mechanisms underlying the reperfusion syndrome may involve cellular calcium overload, over-production of oxygen-derived free radicals, acidosis and/or development of an inflammatory reaction. Numerous pharmacological studies have been conducted over several years designed to limit such reperfusion injury and, consequently, prevent stunning and/or reperfusion-induced arrhythmias. A number of experimental studies in this field have demonstrated that trimetazidine exerts direct anti-ischaemic effects, limiting calcium accumulation and acidosis, inflammation and oxygen-derived free radical production following reperfusion. This agent therefore appears to be particularly promising clinically in the treatment of reperfusion lesions, for example in combination with thrombolysis during the acute phase of myocardial infarction.

Acidosis↗
PubMed1993

Rationale for trimetazidine administration in myocardial ischaemia-reperfusion syndrome.

Although early reperfusion of cardiac tissue is now considered to be the only intervention capable of restoring the various cellular functions altered by ischaemia and preventing progression towards necrosis of myocardial cells, reperfusion is frequently accompanied by various manifestations grouped under the heading of reperfusion syndrome or reperfusion injury. Functional recovery is therefore not immediate, but usually appears after a certain delay following a period of contractile dysfunction (myocardial stunning) lasting for several hours or even days after the start of reperfusion. Characteristic reperfusion-induced arrhythmias are also observed. The cellular mechanisms underlying the reperfusion syndrome may involve cellular calcium overload, over-production of oxygen-derived free radicals, acidosis and/or development of an inflammatory reaction. Numerous pharmacological studies have been conducted over several years designed to limit such reperfusion injury and, consequently, prevent stunning and/or reperfusion-induced arrhythmias. A number of experimental studies in this field have demonstrated that trimetazidine exerts direct anti-ischaemic effects, limiting calcium accumulation and acidosis, inflammation and oxygen-derived free radical production following reperfusion. This agent therefore appears to be particularly promising clinically in the treatment of reperfusion lesions, for example in combination with thrombolysis during the acute phase of myocardial infarction.

Animals↗
PubMed1993

Ultrastructural basis of the free-radical scavenging effect of indapamide in experimental myocardial ischemia and reperfusion.

Reperfusion of acutely ischemic cardiac tissue is associated with several characteristic pathophysiological changes that are generally referred to as "reperfusion injury." It has been hypothesized that some of these changes are mediated by oxygen-derived free radicals. Indapamide, a nonthiazide diuretic, has been shown to exert free-radical scavenging properties comparable to that of alpha-tocopherol. The purpose of the present work was to investigate whether indapamide (IDP) may limit ultrastructural signs of reperfusion injury in an experimental model of myocardial ischemia and reperfusion in isolated rat hearts. Rats received a chronic oral administration of IDP (7 days at 3 mg/kg body weight/day) before excision of the heart. IDP was also added to the perfusion fluid at a final concentration of 10(-4) M. Isolated hearts were perfused under control conditions for 20 min and then submitted to 15 min of global no-flow ischemia, before being reperfused for 15 min. Hearts were fixed by glutaraldehyde perfusion fixation and left ventricular ultrastructure was studied on ultra-thin sections by electron microscopy. Micrographs were taken following a random procedure to obtain a representative overview of the whole section. In the untreated group, marked ultrastructural alterations were observed including contraction bands, disrupted membranes, and swollen mitochondria. In the indapamide-treated group, the degree of morphological injury was significantly lessened. It is concluded that indapamide protects the ultrastructure of ventricular myocytes against reperfusion injury. This effect might be related to the oxygen free-radical scavenging property of the drug.

Animals↗
PubMed1993

Basal cell adhesion to a culture substratum controls the polarized spatial organization of human epidermal keratinocytes into proliferating basal and terminally differentiating suprabasal populations.

The contribution of adhesion to an extracellular matrix in the polarized spatial organization of keratinocytes was studied in dispase-detached cultures stored as floating sheets. Proliferating and terminally differentiating cell populations were, therefore, localized on tissue sections by their DNA-synthesizing ability and involucrin immunostaining, respectively. A progressive reorganization was induced from superposed proliferating and differentiating layers into clusters exhibiting differentiating cells on the outside. Measurements of proliferation and terminal differentiation in detached cultures revealed the progressive disappearance of proliferating cells, followed by an increase in involucrin-positive cells. Attempts to block the spatial reorganization by the addition of components of the extracellular matrix remained unsuccessful. These results suggest that basal anchorage is responsible for the superposition of proliferating and differentiating cells in keratinocyte cultures. They afford new arguments for the induction of terminal differentiation in non-adhesive keratinocytes which exhibit a concomitant modification of cell shape.

3T3 Cells↗
PubMed1992

Evidence of cytosolic iron release during post-ischaemic reperfusion of isolated rat hearts. Influence on spin-trapping experiments with DMPO.

Previous studies of oxygen-derived free radical generation based on spin-trapping methods have shown a signal formed of six bands (sextet) using electron spin resonance spectrometry (ESR) of coronary effluents collected during post-ischaemic reperfusion of isolated hearts perfused with 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The origin of this signal has recently become controversial. In the present study we show that, in the rat, this sextet and cytosolic iron release occur simultaneously, and that this signal can be inhibited by the iron chelator desferrioxamine. It also appears that the iron release is not protein bound, and could therefore have a marked catalytic activity. This may be responsible for the production of an artefactural signal observed as the sextet.

Animals↗
PubMed1992

Design of yeast-secreted albumin derivatives for human therapy: biological and antiviral properties of a serum albumin-CD4 genetic conjugate.

Due to its remarkably long half-life, together with its wide in vivo distribution and its lack of enzymatic or immunological functions, human serum albumin (HSA) represents an optimal carrier for therapeutic peptides/proteins aimed at interacting with cellular or molecular components of the vascular and interstitial compartments. As an example, we designed a genetically engineered HSA-CD4 hybrid aimed at specifically blocking the entry of the human immunodeficiency virus into CD4+ cells. In contrast with CD4, HSA-CD4 is correctly processed and efficiently secreted by Kluyveromyces yeasts. In addition, its CD4 moiety exhibits binding and antiviral in vitro properties similar to those of soluble CD4. Finally, the elimination half-life of HSA-CD4 in a rabbit experimental model is comparable to that of control HSA and 140-fold higher than that of soluble CD4. These results indicate that the genetic fusion of bioactive peptides to HSA is a plausible approach toward the design and recovery of secreted therapeutic HSA derivatives with appropriate pharmacokinetic properties.

Animals↗
PubMed1992

Potential of population pharmacokinetics to reduce the frequency of blood sampling required for estimating kinetic parameters in neonates.

Data obtained from neonates receiving zidovudine as part of a phase I study were used to estimate the population pharmacokinetic parameters of this drug and to determine the minimum number of data points necessary to provide accurate estimates of the kinetic parameters and their variability. Analysis was performed with 541 concentrations of zidovudine, obtained from 32 infants and with a variety of reduced data sets using NONMEM (nonlinear mixed effect model). The reduced data sets were derived by randomly reducing the number of sampling time points per dosing interval and/or by randomly reducing the number of available subjects. We determined that accurate estimates of pharmacokinetic parameters and their variability were obtained with the inclusion of all 32 patients using only two concentration-time points per dose interval, provided that one of the points was obtained during the first 2 h after administration of the drug. The parameters themselves were adequately estimated with only 24 subjects and two concentration-time points per dose interval. We suggest that NONMEM should be used in addition to the traditional pharmacokinetic analysis to obtain more precise information directly in the population of interest with a minimum of blood sampling from each patient. This is especially critical in infants whose blood volumes are limited.

Biological Availability↗
PubMed1991

Zinc deficiency, ethanol, and myocardial ischemia affect lipoperoxidation in rats.

The production of oxygen free radicals can be stimulated by excess iron, cadmium, nickel, and the like. Inversely, copper, zinc, and selenium inhibit production, either via their own action or via antiradical metalloenzymes. The study involved determining the effect of zinc deficiency combined with chronic ethanol administration on the status of blood and tissue free radicals, as well as on cardiac function in isolated, perfused rats' hearts. Animals were fed a basic diet containing residual zinc at 0.2-0.3 ppm. Following a zinc deficiency lasting 5 wk, which during the last 4 wk was accompanied by chronic ethanol administration, hearts were submitted to ischemia for 30 min in vitro, followed by reperfusion. Biochemical analyses (zinc, superoxide dismutase, malondialdehyde, conjugated dienes, and so on) were performed in the blood and in the homogenates of different organs. The experimental zinc deficiency caused a slight decrease of superoxide dismutase activity, accompanied by increased production of peroxidated lipids. Ethanol administration appeared to increase the levels of peroxidated lipids in the heart. Finally, the combination of zinc deficiency and ethanol administration had very harmful effects, especially on lipid peroxidation and contractile function of the isolated, perfused heart in preischemic conditions.

Alkaline Phosphatase↗
PubMed1991

Utilization of human cultured epidermal keratinocytes: irreversibility of the inhibition of proliferation induced in stored detached cultures.

In order to look for the best conditions required for the utilization of cultured epithelium in the treatment of burn wounds, some experiments have been performed studying the storage of dispase-detached cultures. The viability of keratinocytes and, after trypsin dissociation of the cultures, the adhesion and proliferative potential of living keratinocytes were measured. Our laboratory investigations suggest that the storage period of detached cultures has to be kept as short as possible to preserve the keratinocytes' growth potential.

Burns↗
PubMed1991

Photochemically induced charge separation occurring in bacteriorhodopsin. Detection by time-resolved dielectric loss.

Time-resolved dielectric loss (TRDL) measurements are reported for the photochemical excitation of bacteriorhodopsin (bR) in solid films of Halobacterium halobium purple membranes. These measurements provide an independent confirmation for the existence of an important component of charge separation in these membranes after photochemical excitation. The separation of charge is detected by the absorption of microwave energy by the multilayer films of purple membranes in a microwave cavity during flash photolysis experiments. The TRDL method has the advantage of being sensitive to charge separation occurring in both oriented and unoriented films of purple membranes. One disadvantage is that the water content of the samples must be minimized, however, there is some absorbed water present in our electrodeposited solid film samples. To the best of our knowledge, TRDL measurements have not been reported previously for photochemical charge separation in biological membranes. It is significant that an early decay component of TRDL in the 20-microseconds time domain corresponds to the relaxation of the negative charge displacement photocurrent in oriented samples of purple membranes. In addition, a component of charge separation persists during the first several hundred microseconds of the bR photocycle.

Bacteriorhodopsins↗
PubMed1991

Use of polymerase chain reaction for the early detection of HIV infection in the infants of HIV-seropositive women.

Forty-two infants of HIV-seropositive women were evaluated to determine the value of polymerase chain reaction (PCR) in the early detection of HIV infection. All infants less than 6 months old had a simultaneous PCR and culture for HIV. There was an 88% concordance between the two techniques. PCR results showed an excellent correlation with clinical outcome; no PCR-negative patient has subsequently been found to be infected. Occasional false-positive or equivocal PCR results did occur. There was one false-negative culture. PCR is a rapid and sensitive diagnostic test for the early diagnosis of HIV infection in infants at risk, but at present it should be performed in conjunction with other diagnostic tests and good clinical follow-up.

Adult↗
PubMed1991

Inhibition of basal cell proliferation during storage of detached cultured epidermal keratinocyte sheets.

Grafting of human cultured keratinocytes is a promising possibility for the treatment of large burned skin areas. However, during the preparation of cultures for grafting, a necessary step of detachment from culture substratum is performed by incubation with Dispase. In the present paper, we report studies performed to determine whether prolonged storage after detachment would have a detrimental effect on keratinocyte proliferation. Our results show that the number of bromodeoxyuridine-incorporating cells located in the basal layer of the culture gradually diminishes during storage of detached cultured epidermal keratinocyte sheets. Furthermore, the rate of [3H]thymidine incorporation in such detached cultures is also progressively reduced. These observations indicate that the detachment and storage of cultured epidermal keratinocyte sheets for grafting impedes their cell proliferation capacity, as revealed by DNA-synthesis measurements.

Burns↗
PubMed1990

Estimation of disk membrane lateral pressure and molecular area of rhodopsin by the measurement of its orientation at the nitrogen-water interface from an ellipsometric study.

The internal lateral pressure of a bilayer has been estimated by numerous investigators. Most of these measurements were made by using the monolayer technique. In our approach, the disk membrane lateral pressure was estimated by assuming that this value is equal to the surface pressure necessary to maintain the transmembrane orientation of rhodopsin. The orientation of rhodopsin at the nitrogen-water interface was determined by using ellipsometry, which can measure the thickness of the film. By examining surface pressure and ellipsometric isotherms of intact and partially hydrolyzed rhodopsin, we have determined that a lateral pressure of 38 mN/m is necessary to give rhodopsin its natural transmembrane orientation and that surface pressures exceeding 45 mN/m lead to the formation of multilayers in the disk membrane film. At 38 mN/m, pure rhodopsin is found to have a molecular area of 2300 A2.

Animals↗
PubMed1990

Ischemic myocardial cell necrosis: calcium overload or oxygen free-radicals?

Myocardial ischemia results from imbalance between the needs of cardiac tissue and oxygenated blood supplied by the coronary circulation. This imbalance causes a deficit in tissue supplies of oxygen and of metabolizable substrates which leads, to varying degrees according to the severity of the ischemic process, to a decrease in the production of energy. This production rapidly becomes insufficient to ensure normal function. Furthermore, the accumulation of metabolic waste products causes the development of progressive cellular acidosis with inhibitory functional and metabolic effects. These metabolic and functional changes in the cell are accompanied by changes in structure and arrhythmias, as well as modifications in all-energy dependent mechanisms, particularly clearly marked in relation to membrane systems responsible for ion transport. The degree of these various disturbances is dependent upon the severity of the ischemic process as well as its duration. Reversibility can be ensured if normal perfusion is restored early. If reperfusion occurs later, it is generally incapable of ensuring the recovery of normal cell function and the ischemic cell is then destined to necrosis. Among the possible factors responsible for irreversible ischemic injury, an increase in cellular free-calcium concentration or an over-production of oxygen free-radicals, have been largely suggested. A number of therapeutic measures (metabolic or pharmaceutical) have been suggested with the aim of prolonging the duration of tolerable ischemia before the development of irreversible changes which render reperfusion ineffective. This is particularly the case of anti-ischemic drugs, the prototype of which is for instance trimetazidine.

Calcium↗
PubMed1989

Effect of lipid-protein interaction on the color of bacteriorhodopsin.

Detergent solubilization and subsequent delipidation of bacteriorhodopsin (bR) results in the formation of a new species absorbing maximally at 480 nm (bR480). Upon lowering the pH, its absorption shifts to 540 nm (bR540). The pK of this equilibrium is 2.6, with the higher pH favoring bR480 (Baribeau, J. and Boucher, F. (1987) Biochim. Biophysica Acta, 890, 275-278). Resonance Raman spectroscopy shows that bR480, like the native bR, contains a protonated Schiff base (PSB) linkage between the chromophore and the protein. However, the Schiff base vibrational frequency in bR480, and its shift upon deuteration, are quite different from these in the native bR, suggesting changes in the Schiff base environment upon delipidation. Infrared absorption and circular-dichroism (CD) spectral studies do not show any net change in the protein secondary structure upon formation of bR480. It is shown that deprotonation of the Schiff base is not the only mechanism of producing hypsochromic shift in the absorption maximum of bR-derived pigments, subtle changes in the protein tertiary structure, affecting the Schiff base environment of the chromophore, may play an equally significant role in the color regulation of bR-derived pigments.

Bacteriorhodopsins↗
PubMed1989

Stimulation of xylanase synthesis in Cryptococcus albidus by cyclic AMP.

Cryptococcus albidus secretes a xylanase when induced by xylan or beta-methylxyloside, a non-metabolizable inducer, and production of the enzyme is repressed by xylose. The effect of exogenous cAMP on xylanase production was tested under different growth conditions. The cAMP elicited a 1.5 to 2 fold increase in xylanase production during the induction by xylan and B-methylxyloside but did not relieve the repression observed during growth on xylose. Cyclic AMP also affected the growth rate of the cells and did not modulate the activity of pure xylanase in vitro. A 15-nucleotide sequence located upstream from the xylanase gene could be part of a cAMP regulatory sequence.

Base Sequence↗