Mihail Lucian Pascu

EEG/MEG source imaging: methods, challenges, and open issues

We present the four key areas of research—preprocessing, the volume conductor, the forward problem, and the inverse problem—that affect the performance of EEG and MEG source imaging. In each key area we identify prominent approaches and methodologies that have open issues warranting further investigation within the community, challenges associated with certain techniques, and algorithms necessitating clarification of their implications. More than providing definitive answers we aim to identify important open issues in the quest of source localization.

Quinazoline derivatives are efficient chemosensitizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa resistant strains

Amongst the three series of quinazoline derivatives synthesised and studied in this work, some molecules increase the antibiotic susceptibility of Gram-negative bacteria presenting multidrug-resistant phenotypes. N-alkyl compounds induced an increase in the activity of chloramphenicol, nalidixic acid and sparfloxacin, which are substrates of the AcrAB-TolC and MexAB-OprM efflux pumps in clinical isolates. These molecules are able to increase the intracellular concentration of chloramphenicol in efflux pump-overproducing strains. Their activity depends on the antibiotic structure, suggesting that different sites may be involved for the recognition of substrates by a given efflux pump. Quinazoline molecules exhibiting a nitro functional group are more active, and structure-activity relationship studies may be undertaken to identify the pharmacophoric group involved in the AcrB and MexB affinity sites.

Exposure of Chlorpromazine to 266 nm Laser Beam Generates New Species with Antibacterial Properties: Contributions to Development of a New Process for Drug Discovery

Introduction Phenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser. Methods Varying concentrations of Chlorpromazine Hydrochloride (CPZ) (2–20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1–24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200–1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC) - Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923. Results CPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified. Conclusions Exposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is “clean” and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives.

Direct modification of bioactive phenothiazines by exposure to laser radiation

Whereas exposure of combinations of a phenothiazine and bacterium to incoherent UV increases the activity of the phenothiazine, exposure of the phenothiazine alone does not yield an increase of its activity. Because the laser beam energy is greater than that produced by the incoherent UV sources, exposure of phenothiazines to specific lasers may yield molecules with altered activities over that of the unexposed parent. Chlorpromazine, thioridazine and promethazine active against bacteria were exposed to two distinct lasers for varying periods of time. Absorption and fluorescence spectra were conducted prior to and post-exposure and the products of laser exposure evaluated for activity against a Staphylococcus aureus ATCC strain via a disk susceptibility assay. Exposure to lasers alters the absorption/fluorescence spectra of the phenothiazines; reduces the activity of thioridazine against the test bacterium; produces a highly active chlorpromazine compound against the test organism. Exposure of phenothiazines to lasers alters their structure that results in altered activity against a bacterium. This is the first report that lasers can alter the physico-chemico characteristics to the extent that altered bioactivity results. Exposure to lasers is expected to yield compounds that are difficult to make via chemical manipulation methods. A survey of selected patents of interest, even co-lateral for the subject of this article is shortly made.

Characterization of mixtures of compounds produced in chlorpromazine aqueous solutions by ultraviolet laser irradiation: their applications in antimicrobial assays

Abstract. The study reports an investigation of the photoproducts obtained by exposure of chlorpromazine hydrochloride in ultrapure water (concentration 2  mg/mL) to a 266-nm laser beam obtained by fourth harmonic generation from a Nd:YAG laser (6-ns full time width at half maximum, 10-Hz pulse repetition rate). The photoproducts were analyzed by steady-state UV-Vis absorption, laser-induced fluorescence, Fourier transform infrared spectroscopy, and liquid chromatography–tandem time-of-flight mass spectroscopy. Two figures showing pathways that take place during irradiation for obtaining the final products are shown. The quantum yield of singlet oxygen generation by chlorpromazine (CPZ) was determined relative to standard Zn-phthalocyanine in dimethyl sulfoxide. To outline the role of fluorescence in photoproducts formation rates, fluorescence quantum yield of CPZ during exposure to 355-nm radiation (third harmonic of the fundamental beam of Nd:YAG laser) was investigated relative to standard Coumarin 1 in ethanol. The CPZ solutions exposed 60 and 240 min to 266-nm laser beam, respectively, were tested against Staphylococcus aureus ATCC 25923 strain. For 25  μL of CPZ samples irradiated 240 min, a higher diameter of inhibition has obtained against the tested strain than for the 60-min exposed ones.

Properties of polidocanol foam in view of its use in sclerotherapy

Foam sclerotherapy is a widely used method to treat varicose veins disease. It is easy to use and apply, affordable, and has high efficiency that depends on foam stability upon injection. Since sclerotherapy is usually applied in a medical doctors office, one of the most employed methods to generate foam is based on the Tessari technique which uses pumping cycles of liquid and air in-and-out of a double syringe system. Finally, the produced foam exits through a small orifice (∼2mm) at the output of a three-way valve. The present work shows results regarding the factors that may influence foam stability (liquid to air ratio, type of connector, syringe diameter, number of pumping cycles, etc.) of a commonly used sclerosing agent (polidocanol). Furthermore, an effort is made to evaluate the effect of adding different substances on the stability of polidocanol foams (0.5% w/w) by altering the surface tension or/and the bulk and interfacial rheological properties of the fluids. It is shown that adding small concentrations of nonionic surfactants can increase foam stability with just a very small variation of the mean bubbles size.

Spectrophotometric characterization of useful dyes in laser photodynamic therapy

This paper present the physico-chemical properties of some synthetic porphyrin dyes obtained at ZECASIN SA. We have measured the absorption, excitation and fluorescence spectra of these dyes in different solvents. From them we have concluded that the most reliable due for our studies concerning the photodynamic therapy with UV lasers is Zn II- tetrakis-sulfonatophenyl porphyrin.

1064 nm Nd:YAG long pulse laser after polidocanol microfoam injection dramatically improves the result of leg vein treatment: A randomized controlled trial on 517 legs with a three-year follow-up

Objective To assess the efficacy and safety of a new method of clearing varicose veins in the long term. It consists of applying the long-pulsed Nd:YAG laser following the injection of polidocanol microfoam, in two consecutive sessions, treating both legs in full in each session. Method Randomized, Polidocanol-controlled, blind evaluation clinical trial comparing the results between 79 legs treated with Polidocanol and 517 treated with Polidocanol + Laser. Photographs were taken preoperatively and at three months, two years and three years after treatment, as well as patient self-assessments. Results Polidocanol + Laser is much more effective than polidocanol microfoam in clearing venulectasias with a diameter under 4 mm (p < 0.001). After three years, clearing percentages of 89% (Class I veins), 94% (Class II veins) and 95% (Class III veins) are observed, in comparison to 15%, 18% and 17%, respectively when only polidocanol was applied. No unexpected adverse effects were found and 86% of patients stated they were Satisfied or Very Satisfied. Conclusion The method leads to safe, fast and apparently permanent results. The treatment session lasts less than 1 h, and could become a first-choice treatment for the removal of all types of varicose veins with a diameter under 4 mm.

Biological Evaluation of Products Formed from the Irradiation of Chlorpromazine with a 266 nm Laser Beam

Varying concentrations of Chlorpromazine Hydrochloride (CPZ) were exposed to a 266 nm laser beam for varying periods of time ranging from 4 to 24 hrs and the products of irradiation were evaluated for activity against a panel of bacteria that consisted of representatives of Gram-positives and Gram-negatives that expressed different degrees of efflux pump activity, and compared to the parental unexposed compound with prolonged irradiation, whereas the antibacterial activity of the product against Staphylococcus aureus and Escherichia coli strains was many folds greater, no activity against their efflux pumps was noted. The activity of the products of irradiation against Salmonella enterica serovar Enteritidis was slight. However, the products of prolonged irradiation of CPZ produced increasingly significant concentration dependent inhibition of efflux by the Salmonella strains.

Interaction of solutions containing phenothiazines exposed to laser radiation with materials surfaces, in view of biomedical applications

Phenothiazine drugs - chlorpromazine (CPZ), promazine (PZ) and promethazine (PMZ) - were exposed to 266 nm (fourth harmonic of the Nd:YAG pulsed laser radiation) in order to be modified at molecular level and to produce an enhancement of their antibacterial activity. The irradiated samples were analysed by several methods: pH and surface tension measurements, UV-vis-NIR absorption spectroscopy, laser induced fluorescence and thin layer chromatography. The purpose of these investigations was to study and describe the modified properties of the medicines to further investigate their specific interactions with materials such as cotton, polyester and Parafilm M as a model smooth surface. The textile materials may be impregnated with phenothiazines drug solutions exposed to laser radiation in order to be used in treatments applied on the surface of the organism. Some of the phenothiazines solutions exposed prolonged time intervals to laser radiation have much better activity against several bacteria. Therefore, in the paper, it is reported the wetting behaviour of CPZ, PZ and PMZ solutions, irradiated for time intervals between 1 and 240 min, on the surfaces of the three textures in order to draw a conclusion about their wettability as a function of time.