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Biomedical subjects

J Millet

Publications and source records attributed to J Millet.

At least 19 recordsLinked to original sources
PubMed2006

Isolation and in vitro antibacterial activity of astilbin, the bioactive flavanone from the leaves of Harungana madagascariensis Lam. ex Poir. (Hypericaceae).

Harungana madagascariensis is well known for its topical antibacterial properties used in the elaboration of a lot of skin hygiene products. The aim of this study was, on the one hand, to evaluate the in vitro antibacterial activities of aqueous, ethanolic and ethyl acetate crude extracts of Harungana madagascariensis leaves against bacterial strains representative of skin microflora and, on the other hand, to determine the chemical structure of the active compound. Only the ethyl acetate leaf extract presented important antibacterial activity. Its fractionation was carried out by column chromatography using silica gel 60 and it yielded 11 fractions. A bioautographic method, revealed in these fractions the presence of a flavanone as the active compound astilbin or 3-O-alpha-L-rhamnoside-5,7,3',4'-tetrahydroxydihydroflavonol which was identified on the basis of its spectroscopic data. Concerning the antibacterial activity against the representative skin microflora of the armpit and feet, MIC and MBC ranged from 25 to 250 and 100 to 750 microg ml-1, respectively. The results showed that some bacteria considered to be responsible for bad odours at the armpit and feet levels, were destroyed at 200 microg ml-1 (MBC), a concentration sparing most of the useful saprophytic microflora. The minimal inhibitory quantity (MIQs) of astilbin ranged from 50 to 100 microg.

Acetates↗
PubMed2005

Estimation of atrial fibrillatory wave from single-lead atrial fibrillation electrocardiograms using principal component analysis concepts.

A new method for the assessment of the atrial fibrillatory wave (AFW) from the ECG is presented. This methodology is suitable for signals registered from Holter systems, where the reduced number of leads is insufficient to exploit the spatial information of the ECG. The temporal dependence of the bio-electrical activity were exploited using principal component analysis. The main features of ventricular and atrial activity were extracted, and several basis signals for each subspace were determined. Hence, the estimated (AFW) are reconstructed exclusively from the basis signals that formed the atrial subspace. Its main advantage with respect to adaptive template subtraction techniques was its robustness to variations in the QRST morphology, which thus minimised QRST residua. The proposed approach was first validated using a database of simulated recordings with known atrial activity content. The estimated AFW was compared with the original AFW, obtaining correlation indices of 0.774 +/- 0.106. The suitability of this methodology for real recordings was also proven, though its application to a set of paroxysmal AF ECGs. In all cases, it was possible to detect the main frequency peak, which was between 4.6 Hz and 6.9 Hz for the patients under study.

Algorithms↗
PubMed2005

Spatiotemporal blind source separation approach to atrial activity estimation in atrial tachyarrhythmias.

The analysis and characterization of atrial tachyarrhythmias requires, in a previous step, the extraction of the atrial activity (AA) free from ventricular activity and other artefacts. This contribution adopts the blind source separation (BSS) approach to AA estimation from multilead electrocardiograms (ECGs). Previously proposed BSS methods for AA extraction--e.g., independent component analysis (ICA)--exploit only the spatial diversity introduced by the multiple spatially-separated electrodes. However, AA typically shows certain degree of temporal correlation, with a narrowband spectrum featuring a main frequency peak around 3.5-9 Hz. Taking advantage of this observation, we put forward a novel two-step BSS-based technique which exploits both spatial and temporal information contained in the recorded ECG signals. The spatiotemporal BSS algorithm is validated on simulated and real ECGs from a significant number of atrial fibrillation (AF) and atrial flutter (AFL) episodes, and proves consistently superior to a spatial-only ICA method. In simulated ECGs, a new methodology for the synthetic generation of realistic AF episodes is proposed, which includes a judicious comparison between the known AA content and the estimated AA sources. Using this methodology, the ICA technique obtains correlation indexes of 0.751, whereas the proposed approach obtains a correlation of 0.830 and an error in the estimated signal reduced by a factor of 40%. In real ECG recordings, we propose to measure performance by the spectral concentration (SC) around the main frequency peak. The spatiotemporal algorithm outperforms the ICA method, obtaining a SC of 58.8% and 44.7%, respectively.

Algorithms↗
PubMed2003

[Iron chelation in antimalarial therapy].

Rapid development of significant resistance to antimalarial drugs has been a major force driving research to identify and develop new compounds. A number of iron(III)-chelating compounds designed for purposes other than treating malaria have in vitro antimalarial activity stemming from iron deprivation or toxic effects related to free radical release. Several of the iron(III) chelators have been effective in animal models of plasmodial infection. Desferrioxamine has been used successfully against both uncomplicated and severe malaria in humans. Iron-chelating agents seem to be promising therapeutic adjuvants for treatment of severe Plasmodium falciparum malaria infection.

Animals↗
PubMed2002

Solute complexation degree with human serum albumin: biochromatographic approach.

A mathematical model was developed for the study of the D,L-dansylamino acid retention mechanism in reversed-phase liquid chromatography using a C18 column as a stationary phase and human serum albumin (HSA) as an eluent modifier. The solute retention factor is dependent on the HSA concentration in the eluent as well as the binding constant of the guest-HSA complex. A determination of the degree of complexation n(c) (the percent of the complexed guest) could be carried out. Different Van 't Hoff plot shapes of the degree of complexation were observed with different eluent pH, confirming a change in the solute complexation mechanism for physiological pH (between 7-7.5). Enthalpy-entropy compensation was also analysed in relation to this mathematical model to confirm the solute complexation behavior with HSA. These results finally confirmed that at physiological pH and temperature (approximately 35 degrees C) values the HSA was in a favorable structural conformation for its binding with a great majority of drugs.

Chromatography, High Pressure Liquid↗
PubMed2001

Comparison of two hard keratinous substrates submitted to the action of a keratinase using an experimental design.

The influence of temperature, pH, keratinase concentration, substrate concentration and incubation time on the soluble proteins released by a new keratinase from Doratomyces microsporus was studied with a second-order experimental design. Only 15 or 18 spectrophotometric analyses were required to determine the optimal experimental conditions for this keratinase on nail and hoof. This study was carried out by measuring, according to Smith's method, the concentration of soluble proteins released by the enzyme on two substrates: nails and sheep hooves. Results give optimum conditions for the keratinase to release the soluble proteins: pH 8.2, keratinase concentration 0.14% (weight of keratinase lyophilisate/final volume) and substrate concentration 5% (weight of nail powder/final volume) for nails; temperature 38.8 degrees C, pH 9, substrate concentration 5% (weight of hoof powder/final volume) and a 5 h 55 min incubation time for hooves.

Animals↗
PubMed2000

Hydrophylic surfactant-imidazole derivative association studied by RPLC using a hydroorganic solution.

A high-performance liquid chromatographic (HPLC) method for an association study of imidazole derivatives in surfactant micellars using a hydrophilic detergent, i.e. Montanox DF 80 was presented. The thermodynamic results obtained showed that imidazole association in the surfactant micelles was effective over a concentration of surfactant equal to approximatively 4 x 10(-4) mol/l. In addition, an enthalpy-entropy compensation study revealed that the type of interaction between the solute and the RP18 stationary phase was independent of the molecular structure. The thermodynamic variations observed were considered to be the result of equilibrium displacement between the solute and free ethanol (respectively free surfactant) and its clusters (respectively to micelles) created in the mobile phase.

Chromatography, High Pressure Liquid↗
PubMed2000

[Study on the inhibitory activity, in vitro, of baicalein and baicalin against skin fungi and bacteria].

In this paper, we concentrated in examining, in vitro, the antiseptic activity of the baicalein and baicalin upon the seventeen pathogenic skin fungal and sixteen skin bacterial strains, these two flavonic compounds were known principally as the biosubstances of a traditional Chinese medicinal plant: Scutellaria baicalensis. In agar media, the baicalein possessed potent specific activity against the pathogenic yeasts with MICs of 70-100 micrograms/ml; But in the same condition, no inhibitory effect was observed upon dermatophytes and filamentous imperfect fungi for baicalein, and upon all used strains for baicalin. According to the antibacterial test of baicalein, a high efficacy was achieved against certain causative specie of axillary and foot's odour such as Micrococcus sedentarius, Staphylococcus epidermidis, S. hominis and C. xerosis with a MICs inferior to 250 micrograms/ml. The good inhibitory activity of baicalein could be linked to the group hydroxyl (-OH) in position seven of the molecule.

Anti-Infective Agents, Local↗
PubMed1999

Chromatographic approach to study beta-cyclodextrin as a promoter of the penetration of bifonazole into keratinic tissue.

A high-performance liquid chromatographic method for the determination of bifonazole in dimethyl sulfoxide solvent was developed to study its penetration into sheephoof. The analytical method was linear over the concentration range studied, i.e., from 0.1 mg/ml to 1 mg/ml. The relative standard deviation was less than 2%. The data obtained showed that complex forming with beta-cyclodextrin greatly improved the penetration of bifonazole.

Animals↗
PubMed1999

A first order experimental design to assess soluble proteins released by a new keratinase from Doratomyces microsporus on human substrates.

The influence of temperature, pH, keratinase concentration, substrate concentration and incubation time on the soluble proteins released by a new keratinase from Doratomyces microsporus was studied with an experimental design assisted by a simplex method. Only 16 spectrophotometric analyses were required. This study was carried out by measuring, according to Smith's method, the concentration of soluble proteins released by the enzyme on two human substrates: stratum corneum and nails. Results give optimum conditions for the keratinase to release the soluble proteins: Temperature, 28 degrees C; pH, 9.5; keratinase concentration, 0.94% (weight of keratinase lyophilisat/final volume), substrate concentration, 4.9% (weight of skin powder/final volume); and a 5 h 50 min incubation for the stratum corneum. Temperature, 37 degrees C; pH, 9.2, keratinase concentration, 0.11% (weight of keratinase lyophilisat/final volume); substrate concentration, 4.9% (weight of nail powder/final volume) and a 6 h 10 min incubation time for nails.

Algorithms↗
PubMed1999

[The activation patterns during atrial fibrillation in an experimental model].

INTRODUCTION AND OBJECTIVES: In atrial fibrillation, along with the mechanisms of complete reentry and random activation focal activation patterns have been described which have been attributed both to propagation from the endocardium and to the existence of zones with automatic activity. The objectives of present study are to analyze and quantify the atrial activation patterns in an experimental model of atrial fibrillation. MATERIAL AND METHODS: In 11 Langendorff-perfused rabbit hearts atrial fibrillation was induced by atrial burst pacing after right atrial dilatation with an intra-atrial balloon. A multiple electrode consisting of 121 electrodes and positioned in the right atrial free wall was used to construct the activation maps corresponding to 10 segments of 100 ms in 11 different episodes of sustained atrial fibrillation (one per experiment). RESULTS: Of the 110 segments analyzed, 44 (40%) corresponded to random activation patterns. Fifteen segments (14%) corresponded to complete reentry, and in these cases the number of consecutive rotations ranged from 1 to 2.25 (mean 1.4 +/- 0.4). In 49 segments (44%) a single activation front was seen to pass through the recording area without block; alternatively, two simultaneous fronts were recorded that did not re-excite the zone activated by the other. In two segments (2%) there was a focal activation pattern without evidence of propagation from the epicardium surrounding the activated zone. CONCLUSIONS: a) in the experimental atrial fibrillation model used, random activation patterns are more frequent than complete reentry patterns; b) complete reentry can occur in areas smaller than 1 cm2, and c) focal activation during atrial fibrillation is rare.

Analysis of Variance↗
PubMed1999

Antithrombotic and anticoagulant activities of a low molecular weight fucoidan by the subcutaneous route.

Fucoidans (high-molecular-weight sulfated polysaccharides extracted from brown seaweeds) have anticoagulant and antithrombotic effects. They inhibit thrombin by catalyzing both serpins (antithrombin and heparin cofactor II) according to their chemical structures and origins. In this study, a low-molecular-weight (LMW) fucoidan of 8 kDa was obtained by chemical degradation of a high-molecular-weight fraction. The antithrombotic and anticoagulant activities of this new compound were compared to those of a low-molecular-weight heparin (LMWH), dalteparin, following subcutaneous administration to rabbits. This LMW fucoidan exhibited dose-related venous antithrombotic activity, with an ED80 of about 20 mg/kg, 2 h after a single subcutaneous injection. Its activity was comparable to that of dalteparin (close to 200 anti-Xa IU/kg) and was maximal 30 min after a single subcutaneous injection. The activity remained stable (about 70%) from 1 to 4 h after injection, but disappeared by 8 h. The antithrombotic activity was not associated with either a prolongation of the thrombin clotting time (TCT) or an increase in anti-Xa activity, contrary to dalteparin. A slight prolongation of APTT occurred with both compounds. This venous antithrombotic activity was associated with a decrease in ex vivo thrombin generation and with a significant increase in the lag phase in a thrombin generation test. LMW fucoidan thus has potent antithrombotic activity and a potentially weaker haemorrhagic effect (i.e. a smaller effect on coagulation tests and a smaller prolongation of the bleeding time) than dalteparin.

Animals↗
PubMed1999

Further studies on the mechanism for the antithrombotic effects of naroparcil, an orally active thiozyloside compound.

The antithrombotic beta-D-xyloside, naroparcil, has previously been shown to induce a dose-related increase of circulating glycosaminoglycans (GAGs) together with an antithrombin activity (anti-IIa) via heparin cofactor II (HCII) in the rabbit. In order to go further in the mechanisms, the relationship between the antithrombotic activity, the HCII-mediated anti-IIa activity and the plasma GAG content was investigated. We showed that the in vitro specific activity on the inhibition of thrombin by HCII of the plasma GAG extract from naroparcil-treated rabbits was increased by a factor of 60 when compared to controls. In addition, the fractionation of the plasma GAG extract by affinity chromatography on immobilized HCII led to a more potent material whereas the low-affinity fraction was shown to be inactive in thrombin inhibition by HCII. The qualitative analysis of GAGs showed the presence of the deltaDi-4S DS disaccharide, undetectable in control, which accounted for 22% in the unfractionated GAG extract and for 60% in the high affinity fraction. In vitro experiments using immuno-depleted plasma in antithrombin III (ATIII), HCII or both, indicated that the anti-IIa activity of the plasma GAG extract from naroparcil-treated rabbits was mainly due to HCII potentialisation. The unfractionated GAG extract and the high affinity fraction were shown to be antithrombotic in a Wessler-based model in the rat, giving ED80 values of 610 UA/kg and 56 UA/kg respectively whereas the low-affinity fraction was devoid of any antithrombotic activity. These results show that the antithrombotic activity of naroparcil is dependent on modification in the plasma GAG profile which inactivates thrombin via the HCII.

Administration, Oral↗
PubMed1998

Carbaxylosides of 4-ethyl-2-oxo-2H-benzopyran-7-yl as non-hydrolyzable, orally active venous antithrombotic agents.

A (-)-conduritol F derivative was condensed with 4-ethyl-7-hydroxy-2H-1-benzopyran-2-one and converted into (+)-4-ethyl-7-[(1'R,2'S,3'S,4'R)-2',3',4'- trihydroxycyclohexyloxy]-2H-1-benzopyran-2-one ((+)-2). Enantiomer (-)-2 was obtained from a (+)-conduritol F derivative. The carbaxyloside (-)-2 with the L-xylose configuration was more active than (+)-2 in the Wessler's model.

Administration, Oral↗
PubMed1997

Psoralens percutaneous permeation across the human whole skin and the epidermis in respect to their polarity (in vitro study).

8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP) are commonly used in PUVA therapy [psoralen (P) + ultraviolet light A (UVA) irradiation] to treat skin diseases such as psoriasis and vitiligo. In order to predict the choice of the suitable drug(s) for topical applications, with appropriate dosage, percutaneous permeation of the psoralens, in connection with their solubilities and partition coefficients in an octanol/water system, were investigated. The percutaneous penetration experiments were accomplished by the deposit of ethanolic psoralen solution onto human skin and epidermis fragments mounted on Franz cells. Six cells were employed for each psoralen solution and for the whole skin layer as well as for the epidermis. The diffused psoralens in the receptor solution (1.4%, of human serum albumin) were quantified by using high performance liquid chromatography. The solubilities and the partition coefficients (PC) were carried out in an octanol/water system, in triplicate by using spectrofluorimetry. The results demonstrated that cumulated permeated quantities (ng/cm2) over 24 h, across the whole skin and the epidermis were in the following order for the three psoralens: 8-MOP > 5-MOP > TMP. The lipophilicity, expressed via the log PC, was as follows: 1.93 +/- 0.01 (8-MOP), 2.00 +/- 0.01 (5-MOP) and 3.14 +/- 0.01 (TMP). It was inversely correlated with cumulated penetrated amounts over 24 h in both whole skin and epidermis. From these results, TMP could be predicted as the most convenient psoralen for topical applications, because of its weak penetrability. Considering the relationship between psoralens lipophilicity and permeation, only 5-MOP and 8-MOP could be used, topically or orally, especially in the case of generalised skin disorders.

5-Methoxypsoralen↗
PubMed1997

Spectrofluorimetric determination of 5-methoxypsoralen pharmacokinetic in patients' serum.

In medicine, psoriasis and vitiligo are most often treated with PUVA therapy (psoralen plus ultraviolet A). The determination of psoralen in patients' blood is necessary, as it is admitted that the therapeutic efficiency depends on drug concentration in patients' serum. The amount of UVA to administer is inversely proportional to serum peak concentration. High-performance liquid chromatography (HPLC) and gas chromatography are the most employed methods for determining psoralens in patients' serum. The 2 techniques are precise and very sensitive, but time consuming. The aim of this paper is to propose a suitable method which is rapid and simple. It is a spectrofluorimetric technique for 5-methoxypsoralen (5-MOP) determination in the serum of patients treated with PUVA therapy. 5-MOP extraction was carried out with an heptane/dichloromethane mixture (4/1; v/v), according to the Stolk method (1980). A calibration curve (CC) was plotted from 5-MOP concentrations (range 50, 100, 200, 300, 400, 500 ng/ml). The CC was linear with a good coefficient of correlation: r = 0.9971, and a suitable coefficient of variation (CV) of 7.0%. The recovery of the method ranged from 85.3 +/- 4.2 to 108 +/- 4.1%. The assay precision gave a CV ranging from 0.10 to 6.90%, with an error inferior to +/-10%. The method did not reveal any interference from serum components on the 5-MOP emission wavelength. The limit of detection of 5-MOP was 15 ng/ml. The proposed procedure was proved to be appropriate for a rapid determination of 5-MOP in patients' serum. This technique could also be employed for other psoralens used in PUVA therapy (e.g., 8-methoxypsoralen).

5-Methoxypsoralen↗