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Biomedical subjects

S Makki

Publications and source records attributed to S Makki.

At least 19 recordsLinked to original sources
PubMed2001

Methicillin-resistant Staphylococcus aureus: profiles oceans apart--Canadian and Saudi Arabian experiences.

Methicillin-resistant Staphylococcus aureus (MRSA), a pathogen which has increased over the past three decades, is responsible for nosocomial infections and adverse patient outcomes. It is a pathogen of global importance. Rates of patient colonization or infection vary greatly internationally. Lower rates have been observed in Canada and Saudi Arabia compared to the United States and United Kingdom. Although these lower rates may appear reassuring, the trend in MRSA observed in two capital cities, Winnipeg, Canada and Riyadh, Saudi Arabia are consistent with a widespread global increase in MRSA.

Canada↗
PubMed2001

Iron concentrations in human dermis assessed by microdialysis associated with atomic absorption spectrometry.

Until recently, the determination of metallic elements concentrations in normal skin, in vivo, was rare due to the lack of non-invasive techniques. Microdialysis has the advantage of being slightly invasive when applied to the collection in vivo of endogenous or exogenous substances from the skin. Iron is an active element in different cutaneous disorders. The aim of this work was to assess iron by atomic absorption spectrometry (AAS) after the collection of samples by microdialysis from human dermis. A first essential step, before determining the in vivo iron concentration in human dermis, was to establish an experimental protocol applicable to ex vivo as well as in vivo conditions. For this reason, this work deals only with the assessment of iron in ex vivo human dermis. A skin microdialysis technique and a calibration method, the No Net Flux, were used to quantify basal iron concentrations in human dermis and the same method was also used to determine in vitro and ex vivo iron recoveries. No differences were detected between in vitro and ex vivo recoveries. Ex vivo basal iron dermis concentrations ranged from 3.6 to 7.7 microg/l. This study shows that non-invasive microdialysis is an efficient method for sampling iron from human skin. A sensitive and accurate AAS technique was able to assess low iron concentrations in human dermis. The strategy adopted for this work was efficient and appropriate for the determination of iron in human skin and experiments will be carried out in vivo.

Dermis↗
PubMed1997

High-performance thin-layer chromatographic determination of 5-methoxypsoralen in serum from patients.

A simple and rapid high-performance thin-layer chromatographic (HPTLC) determination of 5-methoxypsoralen in serum is necessary for the therapeutic survey of patients treated with Puvatherapy (psoralen+UVA). The assay for this biological fluid involves an extraction with heptane-dichloromethane (4:1, v/v). The analytical method is linear from 50 to 250 ng/ml. This assay range is adequate for analysing human serum, as it corresponds to psoralen concentrations measured in serum from patients treated with psoralen and UVA against psoriasis and vitiligo. The limit of detection is 15 ng/ml. The coefficient of variation was less than 7%.

5-Methoxypsoralen↗
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↗
PubMed1996

Lipophilicity determination of psoralens used in therapy through solubility and partitioning: comparison of theoretical and experimental approaches.

The aim of this study was to determine and to compare experimental and theoretical solubilities (S) as well as partition coefficients (PC) in an octanol/water system of psoralen (P), 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP). For each psoralen, experimental results were performed in triplicate with a spectrofluorimetric technique. The measurements were achieved 10 times for each solution. The obtained order of the solubilities in pure octanol was 5-MOP approximately TMP > P > 8-MOP, while in water-saturated octanol it was expressed as follows: TMP approximately 5-MOP > P > 8-MOP. However, the following order was found for hydrophobicity: TMP > 5-MOP > 8-MOP > P. The solubility ratios (SR) in pure octanol and water were assessed (mean +/- SD): 3.13 +/- 0.01 (P), 2.60 +/- 0.01 (8-MOP), 3.75 +/- 0.01 (5-MOP), and 5.11 +/- 0.01 (TMP). In saturated phases, they were 3.27 +/- 0.01, 2.63 +/- 0.01, 3.85 +/- 0.01, and 5.32 +/- 0.01, respectively. The PCs were determined with low concentrations according to the Dearden and Bresnen32 method and they were 1.67 +/- 0.01, 1.93 +/- 0.01, 2.00 +/- 0.01, and 3.14 +/- 0.01, respectively. Solubility parameters (delta), in Hildebrand unit (H) or in (cal/cm3)1/2, were evaluated. They confirmed the polarity of psoralens, previously expressed through the PC, although the positional isomers (5-MOP and 8-MOP) revealed no difference. Hildebrand's approach to the solubility of regular solutions and Yalkowsky's concept of the solubility of nonelectrolytes and weak electrolytes in an octanol/water system permitted a comparison of the theoretical and experimental results. The perspective of this work is to use the physicochemical properties of the psoralens in practice for insuring convenient experimental assays and the prediction, in vitro, of the percutaneous absorption of these compounds.

5-Methoxypsoralen↗
PubMed1994

Treatment of psoriasis with a new micronized 5-methoxypsoralen tablet and UVA radiation.

Since 1974, phototherapy with psoralen and ultraviolet A (UVA) has been used successfully for the treatment of psoriasis. However, undesirable side effects, including phototoxicity, nausea, stomach pain and headaches, have led investigators to develop new psoralen compounds. 5-Methoxypsoralen (5-MOP) has thus been introduced as an alternative to 8-MOP because of its less pronounced side effects. Since the absorption kinetics and bioactivity of 5-MOP are known to be variable, a new micronized tablet form (5-MOPm) has been developed. In an open randomized study, oral treatments with 5-MOP or 5-MOPm plus UVA radiation were compared in 22 psoriatic patients. Skin type and initial psoriasis area severity index did not differ significantly between treatment groups. Serum concentrations were significantly higher (320 vs 85.82 ng/ml) and occurred earlier (51.8 vs 229.09 min) with 5-MOPm. In addition, a reduction in PASI of more than 90% was achieved sooner (10.63 vs 17.27 treatments) and with a lower cumulative UVA dose (145.89 vs 232.11 J/cm2), in the group treated with 5-MOPm. No side effects were observed with 5-MOPm. Our data indicate that 5-MOPm has a higher bioavailability, clinical efficacy and tolerability than the commonly used 5-MOP.

5-Methoxypsoralen↗
PubMed1993

Serum free 5-methoxypsoralen fraction in health and psoriasis: relationship with human serum albumin concentration.

Human serum albumin is known to be the main carrier of 5-methoxypsoralen (5-MOP) in serum. As hypoalbuminaemia may occur in psoriasis with inflammatory syndrome, variability of the free 5-MOP fraction in serum can be expected. The free 5-MOP fraction was determined by equilibrium dialysis in serum samples obtained from 18 psoriatic patients and 18 control subjects. The median free 5-MOP fraction was not significantly different in the psoriatic group (fu = 4.75%) than in the control group (fu = 5%). However, there was a significantly larger variability of the free fraction in the psoriatic group (2.7 to 8.6%) than in the healthy group (3.2 to 6.8%) (p = 0.002). The binding index of 5-MOP (ratio of bound to free concentrations) was correlated with human serum albumin level (r = 0.784). This work confirms that the 5-MOP fraction in human serum is principally serum albumin dependent, as has been described with in vitro models. Free drug monitoring of 5-MOP is discussed.

5-Methoxypsoralen↗
PubMed1993

Binding of 5-methoxypsoralen to blood fractions. Influence of albumin and free fatty acids: an in vitro study.

The binding of 5-methoxypsoralen (5-MOP) to human serum and blood fractions was studied by equilibrium dialysis associated to high-performance liquid chromatography. 5-MOP serum binding was 95% and kept constant in the range of therapeutic concentrations. Albumin was the main binding protein with one class of binding sites (n = 2.05) and with a moderate affinity constant (Ka = 10,270 M-1). Free fatty acids (FFA) enhanced 5-MOP binding to albumin. Binding to other proteins, alpha 1-acid glycoprotein, gamma-globulins and lipoproteins (LDL, HDL, VLDL) also occurred, but was negligible. 5-MOP bound to red blood cells (RBCs) with a binding index (ratio of intra- to extra-globular 5-MOP concentrations) of 3.84 and 1.48 in buffer and plasma, respectively. 5-MOP distribution in blood was simulated. The free fraction of 5-MOP in blood could be increased in hypoalbuminemia, unchanged in acute inflammation, and decreased by FFA.

5-Methoxypsoralen↗
PubMed1992

A new micronized 5-methoxypsoralen preparation. Higher bioavailability and lower UVA dose requirement.

A new tablet of micronized 5-methoxypsoralen (5-MOP) and a commonly used tablet in therapy (Psoraderm 5) were compared in 12 healthy subjects. Each subject ingested 1.2 mg/kg body weight of each formulation on different days. Bioavailability and phototoxicity of 5-MOP were compared. The results showed that serum and suction blister concentrations were significantly higher and occurred earlier after the oral intake of the micronized preparation. A series of graduated UVA doses were administered, one dose each time the concentration serum peaked, in order to determine the minimum phototoxic dose for each formulation. The micronized preparation induced greater photosensitivity than the unmicronized one. The micronized 5-MOP tablet may thus allow lower doses of UVA to achieve therapeutic results in photochemotherapy and a shortened waiting period following ingestion of drug.

5-Methoxypsoralen↗
PubMed1991

Simple equilibrium dialysis-high-performance liquid chromatographic method for the in vitro assessment of 5-methoxypsoralen bound to human albumin.

Increasingly used in therapeutics, 5-methoxypsoralen (5-MOP), a linear furocoumarin, associated with UVA irradiation (PUVA), is now an established treatment for skin diseases such as vitiligo, mycosis funcoides and particularly psoriasis. Successful PUVA therapy depends on a sufficiently high peak 5-MOP plasma concentration coinciding with the UVA irradiation. However, as with most drugs, only the free plasma fraction is able to enter the target cells and has a pharmacological effect. In this work, the binding of 5-MOP to human albumin was studied in vitro, using a dialysis chamber. Bound and free 5-MOP fractions were quantified by a modification of Stolk's high-performance liquid chromatographic method. Dialysis was performed at 37 degrees C and pH 7.4 for 2 h, against a 4% albumin solution in phosphate buffer. The 5-MOP concentrations used were from 5 x 10(-5) to 5 x 10(-2) g/l in 1 x 10(-1) g/l steps. The 5-MOP bound strongly to human albumin in an unsaturable way. The mean 5-MOP binding to albumin was 95.3%. These results are in accordance with those published by Artuc et al. and not with those of Veronese et al., who found a lower saturable fixation (91%). These two research groups used tritiated 5-MOP. The technique used in this work is simple and inexpensive. It can be employed easily in vivo, e.g., for the assessment of 5-MOP free fractions in different therapeutic conditions.

5-Methoxypsoralen↗
PubMed1991

High-performance liquid chromatographic determination of citropten and bergapten in suction blister fluid after solar product application in humans.

Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a tanning cosmetic product. The aim of this study was to quantify, using high-performance liquid chromatography, the amount of citropten and bergapten in the skin after suntan products application (an emulsion and an oil formulation). A suction blister technique performed of the anterior aspect of the forearm permitted the collection of these two accumulated molecules. Fluorometric and ultraviolet detections were used for citropten and bergapten determinations, respectively.

5-Methoxypsoralen↗
PubMed1991

Peak blistering point: influence on fluid levels of 5-MOP in human skin in vivo after systemic administration.

The concentration of 5-methoxypsoralen (5-MOP) in suction blister fluid (SBF) after oral intake was determined in relation to the peak blistering point. Interstitial fluid was obtained from nine healthy male volunteers by applying mild suction (300-350 mmHg) to the skin of the volar aspect of the forearm. Blisters were raised at three different times: 18 h prior to drug administration (group I); 2 h prior to drug administration (group II); and during drug ingestion (group III). SBF levels of 5-MOP were determined in each group of blisters 2 h after oral administration of 1.2 mg/kg micronized 5-MOP. The results showed a statistically significant difference in the concentrations of 5-MOP between each group of blisters. The highest concentration of 5-MOP in the SBF was found in group III and the lowest in group II blisters. These findings suggest that the point of peak blistering in relation to drug administration needs to be known in each pharmacological study using suction blisters.

5-Methoxypsoralen↗
PubMed1991

Citropten and bergapten suction blister fluid concentrations after solar product application in man.

Citropten (5,7-dimethoxycoumarin) and bergapten (5-methoxypsoralen) are present in bergamot oil which is used as a cosmetic tanning product. The aim of this study was to quantify, using HPLC, the amount of citropten and bergapten in the skin after the application of suntan products (emulsion and oil formulations). A suction blister technique, performed on the volar aspect of the forearm, permitted the collection of these two molecules. The blister fluid concentrations were 37 and 51 ng/ml (emulsion) and 26 and 23 ng/ml (oil), respectively, for citropten and bergapten. Our results show that the suction blister technique could be used for comparing transepidermal penetration of several compounds in vivo in man.

5-Methoxypsoralen↗
PubMed1990

Chronopharmacokinetics of 5-methoxypsoralen.

Diurnal variations in drug pharmacokinetics are a well known phenomenon. Chronopharmacology studies now appear to be attracting increasing interest with a view to establishing an optimum therapeutic prescription. In order to determine possible chronobiological variations of 5-methoxypsoralen (5-MOP) pharmacokinetic, 5-MOP blood concentrations were quantified in 8 healthy subjects after drug ingestion at different times during the day. Stolk's High Performance Liquid Chromatography technique was used to assess the 5-MOP serum concentrations. Each subject underwent three pharmacokinetic studies after oral ingestion of 5-MOP (1.2 mg/kg), in conjunction with a standardized low-lipid meal. The first pharmacokinetic study was started in the morning, the second in the afternoon and the third in the evening. Drug intake was at intervals of 2 days, to avoid drug accumulation. The results showed that the evening intake of the drug induced a higher 5-MOP maximum concentration and a higher 'area under curve' than morning or afternoon ingestion. This study suggests an optimized PUVA therapy, when performed in the evening.

5-Methoxypsoralen↗