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Biomedical subjects

J Blais

Publications and source records attributed to J Blais.

54 records · Page 3Linked to original sources
PubMed1990

Formation of cyclobutane thymine dimers photosensitized by pyridopsoralens: a triplet-triplet energy transfer mechanism.

The 365 nm irradiation of thymine thin films in the presence of pyridopsoralens is shown to induce the formation of cyclobutane thymine dimers, in contrast to other compounds such as 8- and 5-methoxypsoralen. In order to elucidate the mechanism of such a photosensitized reaction, we have determined the energy of the lowest triplet state (T1) of these compounds, using phosphorescence spectroscopy and CNDO/S quantum chemistry calculations. The T1 energy values were found to be significantly higher for pyridopsoralens--up to 0.3 eV--than for 8- and 5-methoxypsoralen (approximately 2.8 eV), which are not able to photoinduce cyclobutane thymine dimers. The determination of the relative efficiency of cyclobutane thymine dimer formation was performed using chromatographic analysis. A good correlation was found between the energy of the T1 state of the psoralen derivatives and the related cyclobutane thymine dimer formation. Moreover, the photosensitized cyclobutane thymine dimer formation appeared to be temperature-dependent. Our results are consistent with a mechanism involving a triplet energy transfer from the pyridopsoralen to thymine.

Energy Transfer↗
PubMed1988

Relative affinity of 5-methoxypsoralen and 8-methoxypsoralen towards beta-cyclodextrin: a fluorescence, circular dichroism and chromatographic study.

The relative affinity of 5-methoxypsoralen (5-MOP) and 8-methoxypsoralen (8-MOP) towards beta-cyclodextrin, a good model for the study of lipophilic interactions in biological systems and a potential drug carrier, has been investigated using spectroscopic and chromatographic methods. The fluorescence emission of 5-MOP in aqueous solution containing beta-cyclodextrin (10(-2) M) is found to be markedly blue shifted and enhanced by a factor of 6 whereas no significant changes are observed for 8-MOP. The existence of an induced circular dichroism is evidence for the formation of a 1:1 inclusion complex (association constant K = 400 +/- 50 M-1). Moreover, chromatographic results obtained with a beta-cyclodextrin linked stationary phase are consistent with our spectroscopic results and might have interesting analytical implications. These results clearly demonstrate that, in contrast to 8-MOP, 5-MOP exhibits a strong affinity for hydrophobic medium. Interesting pharmacological and analytical applications may result from the possible inclusion of psoralen derivatives into beta-cyclodextrin.

5-Methoxypsoralen↗
PubMed1984

The metabolism of 8-methoxypsoralen by Saccharomyces cerevisiae. Evidence for an inducing effect of ethanol.

The metabolism of 8-methoxypsoralen (8-MOP) by the yeast Saccharomyces cerevisiae has been investigated in order to determine if this cell system could provide a simple model to study the metabolism of new photosensitizing drugs in vitro. 8-MOP was found to be rapidly metabolized by S. cerevisiae in non growing conditions. A metabolite was detected which exhibits a structure similar to that of a metabolite previously isolated in dog and man. Ethanol showed a strong inducing effect on 8-MOP metabolization.

Biotransformation↗
PubMed1983

Photobiological activity of suction blister fluid from patients treated with 8-methoxypsoralen.

Suction blister fluid was collected from normal human volunteers before (SBF) and 2 h after (SBF 8-MOP) oral 8-methoxypsoralen (0.6 mg/kg) ingestion without irradiation. In SBF 8-MOP the concentration of 8-MOP was 150 ng/ml, and fluorescent metabolites were also present. The toxicity of SBF 8-MOP was then determined with and without UV-A irradiation in the diploid strain D7 of the yeast Saccharomyces cerevisiae which is suitable for the detection of lethal, mutagenic and recombinogenic events. It was compared with that of SBF, SBF with 8-MOP added in vitro (150 ng/ml) and 8-MOP (150 ng/ml) in water. SBF showed no effect with UV-A doses up to 360 kJ m-2; SBF 8-MOP showed a slight decrease in survival and a dose-dependent increase in nuclear mutations, mitotic gene conversion and crossing over; SBF with 8-MOP added in vitro showed increased photobiological activity compared with SBF 8-MOP. This photobiological activity was increased by a factor of six when using 8-MOP in water. These results indicate a different bioavailability of 8-MOP in water and in interstitial fluid containing proteins. The metabolites of 8-MOP in human skin did not increase the photobiological activity of the drug. We conclude that the 8-MOP present in human skin during PUVA therapy is mutagenic and recombinogenic for eukaryotic cells.

Biological Availability↗
PubMed1982

[Serum angiotensin converting enzyme activity in sarcoidosis. A review of seventy cases].

The serum angiotensin converting enzyme (ACE) activity was assayed in seventy untreated patients with sarcoïdosis. Results were considered abnormal if they exceeded 34,5 U/ml. (SEM + 250). Increased ACE activity was found in 55,7% of the patients. Most of these patients had either Stage II or disseminated disease. Significant decreases in ACE activity always occurred during remission, whether spontaneous or induced by corticosteroids. In most patients with persistant roentgenologic features ACE activity was still high six months after onset. No correlations were found between serum ACE activities and lymphocytosis in bronchial washing samples. We conclude that, while serum ACE activity assays are not of significant diagnostic utility in patients with sarcoidosis, they are helpful for monitoring the course of the disease.

Adult↗
PubMed1982

[Echogenic gallbladder sludge: ultrasonographic study and pathological significance in 74 cases (author's transl)].

Correlations between ultrasonographic and clinical and histological findings were studied in 74 patients presenting with echogenic gallbladder sludge. The majority of patients in whom bile examinations had been performed had either pus, blood, biliary sediment, or microcalculi in the bile, but precise identification of the nature of the sludge does not appear to be possible on ultrasonography. Calculi were present in the gallbladder in 39 p. cent of these patients, only 9 p. cent demonstrating the presence of sludge without established liver or biliary lesions. This ultrasonographic image appears, therefore, to be a clinically significant valid finding.

Adult↗
PubMed1980

[Exclusive parenteral nutrition. Results in 45 acute exacerbations of Crohn's disease (author's transl)].

Exclusive parenteral nutrition (EPN) was used in severe acute exacerbations of Crohn's disease, on 36 occasions for an acute episode during the course on the disease, in 8 in preparation for surgery and twice for digestive fistulae. The mean duration of EPN was of 33 days. Calorie intake was 65 to 74 cal/kg/d, the nitrogen part varying from 9 to 17 g/d. Lipids accounted for 40 to 60% of the total carbohydrate-lipid calorie intake in order to avoid fatty infiltration of the liver. Complications which occur, above all at the beginning of treatment, and due in part to insertion of the catheter and secondly to metabolic problems, have since been corrected. There was a weight gain of 5.78 +/- 1.1 kg, an increase in plasma albumin of 6.1 +/- 1.5 g/l and a return to normal in the number and weight of stools. In terms of the course of the disease, EPN offered excellent preparation for surgery and remission or stabilisation of acute exacerbations in young forms of the disease, in particularly with colonic involvement.

Crohn Disease↗
PubMed1975

[Treatment of an old temporomandibular joint luxation].

The authors present a case of longstanding luxation of the left temporo-mandibular joint, leading to prognathism with lateral deviation. The functional and aesthetic problems due to this deformity were advantageously corrected by saggital cleavage of the ascending left ramus, after previous orthodontic treatment and study on Chateau's articulator.

Adult↗
PubMedDate not supplied

Importance of the ionization states of m-THPC for its HPLC fluorescence detection.

An original, rapid and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the detection of 5, 10, 15, 20 tetra-meso-hydroxyphenylchlorine (m-THPC), a photosensitizer used in the photodynamic therapy (PDT) of cancers. Chromatographic separation was carried out on a C(8) Zorbax column (80 x 4 mm, 5 microm). The mobile phase was an ethanol/aqueous sulphuric acid, pH 2.0 (65/35 v/v), in an isocratic mode yielding to rapid analysis (3.1 min) with narrow peaks. As the fluorescence intensity was found to be highly pH-dependent and to increase with pH values, a post-column device prior to the fluorescence detection (lambda(exc) = 423 nm, lambda(em) = 650 nm) was used to allow the addition of a 0.05 mol/L Na(2)HPO(4) solution to the mobile phase. Compared to standard conditions, a 300% increase of the fluorescence intensity was obtained for optimized operating conditions using experimental design. The validation of this analytical method showed that the response function was linear for concentrations up to 1000 microg/L (1.47 x 10(-6) mol/L) with a detection limit of 188 pg (S/N = 3).

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Photochemotherapy using pyridopsoralens.

Aiming to decrease the acute side effects and genotoxic hazards of PUVA, pyrido (3,4-C) psoralen (PP) and 7-methyl pyrido (3,4-C) psoralen (MPP) were synthesized and studied. Their UVA maximum absorption lies at 325 and 330 nm, respectively. Their photostability is comparable to that of 8-MOP. They complex to DNA in the dark, and, in the presence of UVA, produce only monoadditions to DNA, as shown by fluorescence and DNA denaturation-renaturation studies. In diploid eukaryotic yeast they are more effective than 8-MOP for the induction of lethal effects and mitochondrial damage. Their mutagenic activity per unit dose of UVA is in the same range as that of 8-MOP. However, per viable cell they are clearly less mutagenic than 8-MOP. This difference is also observed for recombinogenic activity. No oxygen effect is observed. In mammalian cells the following ranges of effectiveness are found: inhibition of DNA synthesis in human fibroblasts: MPP greater than PP greater than 8-MOP; mutagenic activity in V79 Chinese hamster cells: MPP greater than PP greater than 8-MOP; cell transforming ability in C3H embryonic mouse cells: MPP greater than 8-MOP greater than PP as a function of UVA dose, and: 8-MOP greater than MPP greater than PP as a function of survival; induction of sister chromatic exchanges (SCE) per unit dose: MPP greater than PP greater than 8-MOP in the linear part of the induction curve, and : 8-MOP greater than PP greater than MPP at the maximum level of SCE obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxypsoralen↗
PubMedDate not supplied

A comparative study of the cellular uptake, localization and phototoxicity of meta-tetra(hydroxyphenyl) chlorin encapsulated in surface-modified submicronic oil/water carriers in HT29 tumor cells.

The poor selectivity of photosensitizers for tumor tissue remains a drawback in photodynamic therapy (PDT) and could be improved by adapted formulations. The cellular uptake, localization and phototoxicity of meta-tetra(hydroxyphenyl)chlorin (mTHPC) encapsulated in submicronic colloidal carriers have been studied in macrophage-like J774 cells and HT 29 human adenocarcinoma cells. Nanocapsules with an external layer made of poly(D,L lactic acid) (PLA NCs), PLA grafted with polyethylene glycol (PLA-PEG NCs), PLA coated with poloxamer 188 (polox PLA NCs) and oil/water nanoemulsion (NE) have been examined. The cellular uptake by J774, as determined by microspectroflorimetry, is reduced with mTHPC encapsulated into surface-modified NCs--PLA-PEG and polox PLA--compared with naked PLA, indicating a possible limitation of the clearance of such carriers by the reticuloendothelial system. Encapsulation also modifies the interaction between mTHPC and HT29 cells. Compared with the manufacturer's solution (PEG, ethanol, water), the cellular uptake is strongly reduced. However, the HT29 phototoxicity is much less affected and a protecting effect against plasma proteins is observed. Fluorescence microscopy reveals a specific punctate fluorescence pattern with PLA-PEG and polox PLA NCs in contrast to a more diffuse distribution with NE and solution, indicating that photodamage targeting could be different. These findings suggest that photosensitizers encapsulated into surface-modified nanocapsules could be a promising approach for improving PDT efficacy and this has to be confirmed in vivo.

Animals↗