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991.
In Vivo Fluence Rate Effect in Photodynamic Therapy of Early Cancers with Tetra(m-hydroxyphenyl)chlorin 总被引:1,自引:0,他引:1
Snezana Andrejevic Blant Alain Woodtli Georges Wagnières Charlotte Fontolliet Hubert van den Bergh Philippe Monnier 《Photochemistry and photobiology》1996,64(6):963-968
Abstract— Several parameters affect clinical trials in photodynamic therapy and influence the therapeutic outcome. Beside drug dose, light dose, drug-light interval and other variables, the fluence rate is a parameter that can influence the therapeutic results. In this study we have evaluated the fluence rate effect with a second-generation photosensitizer, tetra( m -hydroxyphenyl)chlorin (mTHPC) using a 7,12-dimethylbenz(a)anthracene induced early squamous cell carcinoma of the Syrian hamster cheek pouch as a tumor model. Following injection of 0.5 mg/kg of mTHPC, irradiation tests were performed at two drug-light intervals, 4 and 8 days. Wavelength and light dose were adapted from those applied routinely in clinical trials. Irradiations at 652 nm were carried out with fluences ranging from 8 to 20 J/cm2 delivered at fluence rates of 15 and 150 mW/cm2 . Similar tests were also performed at 514 nm with a fluence of 80 J/cm2 delivered at fluence rates ranging from 25 to 125 mW/cm2 . At both wavelengths and drug-light intervals for a given fluence, the higher fluence rates resulted in less tissue damage in tumor and healthy mucosae. However, the lower fluence rates yielded slightly less therapeutic selectivity. This study confirms that the fluence rate is of major importance in clinical PDT. 相似文献
992.
Quantitative liquid chromatographic determination of cefatrizine in serum and urine by fluorescence detection after post-column derivatization 总被引:1,自引:0,他引:1
E Crombez G Van der Weken W Van den Bossche P De Moerloose 《Journal of chromatography. A》1979,177(2):323-332
A fast, specific and sensitive high-performance liquid chromatographic procedure for the determination of cefatrizine, an orally active cephalosporin, in serum and urine is proposed. The drug is determined by the internal standard method, using cephradine as the internal standard. The separation is carried out on a reversed-phase column, filled with octadecylsilane chemically bonded microparticles. The eluent is a mixture of acetonitrile with 0.025 M sodium phosphate buffer (pH 7). Quantitation is effected by fluorescence detection of the fluorophores formed after post-column derivatization with fluorescamine in a packed-bed reactor. The chromatographic conditions and the conditions for the post-column derivatization are discussed. The method has been applied to serum and urine samples, which were analysed after deproteinization with trichloroacetic acid and injection of the clear supernatant. The accuracy and reproducibility of the procedure were investigated by the determination of the cefatrizine content in spiked serum and urine samples. 相似文献
993.
Alexey A. Goryunkov Igor V. Kuvychko Donald L. Dick Steven H. Strauss Olga V. Boltalina 《Journal of fluorine chemistry》2003,124(1):61-64
The high temperature reaction of C60 with silver(I) trifluoroacetate followed by 500 °C sublimation and subsequent HPLC purification has led to the isolation of the five trifluoromethyl[60]fullerenes C60(CF3)n (n=2, 4, 6, 8, 10). Four of them have >90% compositional purity. Two of the compounds, C60(CF3)4 and C60(CF3)6, were obtained as C1-symmetry isomers with >90% isomeric purity, and a sample of C60(CF3)2 also contained ca. 15-20% of a Cs-symmetry isomer of C60(CF3)4. The new compounds were characterized by IR and EI mass spectrometry (all five compounds), NMR spectroscopy (C60(CF3)2, C60(CF3)4, and C60(CF3)6), and 2D COSY NMR spectroscopy (C60(CF3)4 and C60(CF3)6). Calculations at the AM1 and DFT levels of theory have led to the prediction of the most likely structures for C60(CF3)2, C1-C60(CF3)4, Cs-C60(CF3)4, and the two most likely structures of C1-C60(CF3)6. 相似文献
994.
Pharmacokinetics of Tetra (m-hydroxyphenyl)chlorin in Human Plasma and Individualized Light Dosimetry in Photodynamic Therapy 总被引:2,自引:0,他引:2
Thomas Glanzmann Christophe Hadjur Matthieu Zellweger Pierre Grosjean Martin Forrer Jean-Pierre Ballini Philippe Monnier Hubert van den Bergh Chang Kee Lim Georges Wagnières 《Photochemistry and photobiology》1998,67(5):596-602
The pharmacokinetics of the photosensitizer 5,10,15,20-tetra( m -hydroxyphenyl) chlorin(mTHPC) was investigated in the plasma of 20 patients by absorption and fluorescence spectroscopy. The temporal behavior was characterized by a rapid decrease in concentration during the first minutes after intravenous injection of 0.15 mg/kg mTHPC. A minimum concentration in the plasma was reached after about 45 min. The drug concentration then increased again, attaining a maximum after about 10 h, after which it decreased again with a halflife of about 30 h. Irradiation tests in the oral cavity at different time intervals after the injection revealed that the tissue re-action was only partially correlated with the mTHPC plasma level. The tissue response was stronger at later drug-light intervals (1–4 days) than during the first hours after injection even though the mTHPC plasma concentration was higher at the shorter times. Relative mTHPC concentrations were also measured in the mucosae of the oral cavity, the esophagus and the bronchi of 27 patients by light-induced fluorescence spectroscopy using an optical fiber-based spectrometer. These measurements were performed prior to photodynamic therapy (PDT), 4 days after injection of the photosensitizer. Highly significant linear correlations were found between the relative mTHPC concentrations in the mucosae of these three organs. Likewise, the plasma levels of mTHPC measured just before PDT were significantly correlated with the mTHPC concentrations in the three types of mucosae mentioned above. These results indicate that mTHPC plasma levels measured just before PDT can be used for PDT light dosimetry. 相似文献
995.
The coalescence frequency in emulsions containing droplets with a low viscosity (viscosity ratio approximately 0.005) in simple shear flow has been investigated experimentally at several volume fractions of the dispersed phase (2%-14%) and several values of the shear rate (0.1-10 s(-1)). The evolution of the size distribution was monitored to determine the average coalescence probability from the decay of the total number of droplets. Theoretically models for two-droplet coalescence are considered, where the probability is given by P(c)=exp(-tau(dr)tau(int)). Since the drainage time tau(dr) depends on the size of the two colliding droplets, and the collision time tau(int) depends on the initial orientation of the colliding droplets, the calculated coalescence probability was averaged over the initial orientation distribution and the experimental size distribution. This averaged probability was compared to the experimentally obtained coalescence frequency. The experimental results indicate that (1) to predict the average coalescence probability one has to take into account the full size distribution of the droplets; (2) the coalescence process is best described by the "partially mobile deformable interface" model or the "fully immobile deformable interface" model of Chesters [A. K. Chesters, Chem. Eng. Res. Des. 69, 259 (1991)]; and (3) independent of the models used it was concluded that the ratio tau(dr)tau(int) scales with the coalescence radius to a power (2+/-1) and with the rate of shear to a power (1.5+/-1). The critical coalescence radius R(o), above which hardly any coalescence occurs is about 10 microm. 相似文献
996.
Glanzmann T Forrer M Blant SA Woodtli A Grosjean P Braichotte D van den Bergh H Monnier P Wagnières G 《Journal of photochemistry and photobiology. B, Biology》2000,57(1):22-32
The pharmacokinetics (PK) of the photosensitizer tetra(m-hydroxyphenyl)chlorin (mTHPC) was measured by optical fiber-based light-induced fluorescence spectroscopy (LIFS) in the normal and tumoral cheek pouch mucosa of 29 Golden Syrian hamsters with chemically induced squamous cell carcinoma. Similar measurements were carried out on the normal oral cavity mucosa of five patients up to 30 days after injection. The drug doses were between 0.15 and 0.3 mg per kg of body weight (mg/kg), and the mTHPC fluorescence in the tissue was excited at 420 nm. The PK in both human and hamster exhibited similar behavior although the PK in the hamster mucosa was slightly delayed in comparison with that of its human counterpart. The mTHPC fluorescence signal of the hamster mucosa was smaller than that of the human mucosa by a factor of about 3 for the same injected drug dose. A linear correlation was found between the fluorescence signal and the mTHPC dose in the range from 0.075 to 0.5 mg/kg at times between 8 and 96 h after injection. No significant selectivity in mTHPC fluorescence between the tumoral and normal mucosa of the hamsters was found at any of the applied conditions. The sensitivity of the normal and tumoral hamster cheek pouch mucosa to mTHPC photodynamic therapy as a function of the light dose was determined by light irradiation at 650 nm and 150 mW/cm2, 4 days after the injection of a drug dose of 0.15 mg/kg. These results were compared with irradiations of the normal oral and normal and tumoral bronchial mucosa of 37 patients under the same conditions. The reaction to PDT of both types of human mucosae was considerably stronger than that of the hamster cheek pouch mucosa. The sensitivity to PDT became comparable between hamster and human mucosa when the drug dose for the hamster was increased to 0.5 mg/kg. A significant therapeutic selectivity between the normal and neoplastic hamster cheek pouch was observed. Less selectivity was found following irradiations of normal mucosa and early carcinomas in the human bronchi. The pharmacodynamic behavior of mTHPC was determined by test irradiations of the normal mucosa of hamsters and patients between 6 h and 8 days after injection of 0.5 and 0.15 mg/kg in the hamsters and the patients, respectively. The normal hamster cheek pouch showed a maximum response to irradiation 6 h after injection and then decreased continuously to no observable reaction at 8 days after injection. The reaction of the normal human oral mucosa, however, showed an increasing sensitivity to the applied light between 6 h and 4 days after mTHPC injection and then decreased again at 8 days. The hamster model with the chemically induced early squamous cell cancer in the cheek pouch thus showed some similarity to the early squamous cell cancer of the human oral mucosa considering the PK. However, a quantitative difference in fluorescence signal for identical mTHPC doses as well as a significant difference in pharmacodynamic behavior were also observed. The suitability of this animal model for the optimization of PDT parameters in the clinic is therefore limited. Hence great care must be taken in screening new dyes for PDT of early squamous cell cancer of the upper aerodigestive tract based upon observables in the hamster cheek pouch model. 相似文献
997.
G. den Boef und A. Daalder 《Fresenius' Journal of Analytical Chemistry》1960,172(5):360-362
Zusammenfassung Quantitative Bestimmungen von geringen Mengen Chrom(III) können durch Oxydation mit Kaliummanganat durchgeführt werden. Da die 2 CrIII + 3 MnVI 2 CrVI + 3 MnVI nur langsam verläuft, soll man der alkalischen CrIII-Lösung einen Überschuß Manganat zusetzen und diesen Überschuß nach einiger Zeit mit AsIII-Lösung zurücktitrieren.III. Mitteilung: diese Z. 167, 430 (1959).Herrn F. Heyting danken wir für die Durchführung einiger Versuche während dieser Arbeit. 相似文献
998.
van Loo B Spelberg JH Kingma J Sonke T Wubbolts MG Janssen DB 《Chemistry & biology》2004,11(7):981-990
The enantioselectivity of epoxide hydrolase from Agrobacterium radiobacter (EchA) was improved using error-prone PCR and DNA shuffling. An agar plate assay was used to screen the mutant libraries for activity. Screening for improved enantioselectivity was subsequently done by spectrophotometric progress curve analysis of the conversion of para-nitrophenyl glycidyl ether (pNPGE). Kinetic resolutions showed that eight mutants were obtained with up to 13-fold improved enantioselectivity toward pNPGE and at least three other epoxides. The large enhancements in enantioselectivity toward epichlorohydrin and 1,2-epoxyhexane indicated that pNPGE acts as an epoxyalkane mimic. Active site mutations were found in all shuffled mutants, which can be explained by an interaction of the affected amino acid with the epoxide oxygen or the hydrophobic moiety of the substrate. Several mutations in the shuffled mutants had additive effects. 相似文献
999.
Vanhees I Van den Bergh V Schildermans R De Boer R Compernolle F Vinckier C 《Journal of chromatography. A》2001,915(1-2):75-83
In this paper a method is described for determining and quantifying the degradation products of the reaction of alpha-pinene with hydroxyl radicals. The study is carried out in a fast-flow reactor equipped with a specially designed microwave cavity (type Surfatron) allowing to operate at pressures up to 100 Torr (1 Torr=133.322 Pa). The semi-volatile products are collected on a liquid nitrogen trap (LN2 trap) coated with a 2,4-dinitrophenylhydrazine (2,4-DNPH) solution and the batch samples are subsequently analyzed by HPLC. In order to perform quantitative measurements the batch samples contained two internal standards: benzaldehyde-2,4-DNPH and tolualdehyde-2,4-DNPH. In the experiments carried out at 50 Torr and 100 Torr, HPLC measurements showed that the semi-volatile products formaldehyde, acetaldehyde, acetone, campholenealdehyde and pinonaldehyde could be quantified as oxidation products for the alpha-pinene/OH reaction, with pinonaldehyde being the main product. Assuming that all these five oxidation products have the same collection efficiency on the LN2 trap, one arrives at the following relative product yields (expressed in mol %) at 50 and 100 Torr, respectively: 9.7+/-0.7 and 6+/-5 for formaldehyde; 1.1+/-0.1 and 0.9+/-0.5 for acetaldehyde; 16+/-1 and 6+/-2 for acetone; 11+/-2 and 5.5+/-0.7 for campholenealdehyde; 63+/-3 and 82+/-7 for pinonaldehyde. 相似文献
1000.
Catalina MI van den Heuvel RH van Duijn E Heck AJ 《Chemistry (Weinheim an der Bergstrasse, Germany)》2005,11(3):960-968
Electrospray ionization mass spectrometry (ESI-MS) is a valuable tool in structural biology for investigating globular proteins and their biomolecular interactions. During the electrospray ionization process, proteins become desolvated and multiply charged, which may influence their structure. Reducing the net charge obtained during the electrospray process may be relevant for studying globular proteins. In this report we demonstrate the effect of a series of inorganic and organic gas-phase bases on the number of charges that proteins and protein complexes attain. Solution additives with very strong gas-phase basicities (GB) were identified among the so-called "proton sponges". The gas-phase proton affinities (PA) of the compounds that were added to the aqueous protein solutions ranged from 700 to 1050 kJ mol(-1). Circular dichroism studies showed that in these solutions the proteins retain their globular structures. The size of the proteins investigated ranged from the 14.3 kDa lysozyme up to the 800 kDa tetradecameric chaperone complex GroEL. Decharging of the proteins in the electrospray process by up to 60 % could be achieved by adding the most basic compounds rather than the more commonly used ammonium acetate additive. This decharging process probably results from proton competition events between the multiply protonated protein ions and the basic additives just prior to the final desolvation. We hypothesize that such globular protein species, which attain relatively few charges during the ionization event, obtain a gas-phase structure that more closely resembles their solution-phase structure. Thus, these basic additives can be useful in the study of the biologically relevant properties of globular proteins by using mass spectrometry. 相似文献