INVOLVEMENT OF SINGLET OXYGEN IN THE PHOTOTOXICITY MECHANISM FOR A METABOLITE OF PIROXICAM

It has been previously shown that a metabolite of piroxicam but not piroxicam itself causes phototoxicity to cells in vitro after exposure to UVA (320–400 nm) radiation. The phototoxicity mechanism for this metabolite, 2-methyl-4-oxo-2H-l,2-benzothiazine-l,l-dioxide (Compound I), was investigated. In vitro phototoxicity to human mononuclear cells was assayed using 0.5 m M Compound I and UVA radiation. The UVA fluence required for phototoxicity of Compound I was lower by a factor of 2-3 in D₂O buffer compared to H₂O buffer. Superoxide dismutase and mannitol, which remove O₂^- and OH", respectively, do not decrease the phototoxicity. The photodecomposition of Compound I was inhibited by sodium azide, enhanced by human serum albumin and unaffected by mannitol. Stable photoproducts of Compound I were not toxic to the cells. The quantum yield of singlet oxygen based on its emission at 1270 nm was 0.19 and 0.35 for Compound I and s2 ± 10^-3 and 10^-2 for piroxicam in D₂O and C₆H₆, respectively. While the extremely low quantum yield for singlet oxygen from piroxicam appears to account for its lack of phototoxicity, the phototoxicity mechanism for its metabolite, Compound I, most likely does involve singlet oxygen.     

Ab initio calculations and vibrational energy level fits for the lower singlet potential-energy surfaces of C3

Ab initio multireference configuration interaction potential energy surfaces are computed for the eight lowest singlet surfaces of C(3). These reveal several important features, including several conical intersections in linear, nonlinear, and equilateral triangle geometries. These intersections are important because, particularly for the excited A (1)Pi(u) state, reasonable ab initio results could only be obtained by including nearby, near degenerate, (1)Sigma(u) (-) and (1)Delta(u) states that cross the A (1)Pi(u) state around 4500 cm(-1) above the equilibrium geometry, and a (1)Pi(g) state whose potential in turn crosses the other states about 2000 cm(-1) further up. These states are probably responsible for the complexity of the shorter wavelength UV absorption spectrum of C(3). The computed potential energy surface for the ground, X (1)Sigma(g) (+), state and for the lowest two excited singlet surfaces (which both correlate with the A (1)Pi(u) state in a collinear geometry) are fitted to analytic functional forms. Vibrational energy levels are calculated for both states, taking account of the Renner-Teller coupling in the excited A (1)Pi(u) state. The potential parameters for both states are then least-squares fitted to experimental data. The ground-state fit covers a range of approximately 8500 cm(-1) above the lowest level, and reproduces 100 observed vibrational levels with an average error of 2.8 cm(-1). The A (1)Pi(u) state surfaces cover a range of 3250 cm(-1) above the zero-point level, and reproduce the 44 observed levels in this range with an average error of 2.8 cm(-1).     

Narrow band quantitative and multivariate electroencephalogram analysis of peri-adolescent period

ABSTRACT: BACKGROUND: The peri-adolescent period is a crucial developmental moment of transition from childhood to emergent adulthood. The present report analyses the differences in Power Spectrum (PS) of the Electroencephalogram (EEG) between late childhood (24 children between 8 and 13 years old) and young adulthood (24 young adults between 18 and 23 years old). RESULTS: The narrow band analysis of the Electroencephalogram was computed in the frequency range of 0--20 Hz. The analysis of mean and variance suggested that six frequency ranges presented a different rate of maturation at these ages, namely: low delta, delta-theta, low alpha, high alpha, low beta and high beta. For most of these bands the maturation seems to occur later in anterior sites than posterior sites. Correlational analysis showed a lower pattern of correlation between different frequencies in children than in young adults, suggesting a certain asynchrony in the maturation of different rhythms. The topographical analysis revealed similar topographies of the different rhythms in children and young adults. Principal Component Analysis (PCA) demonstrated the same internal structure for the Electroencephalogram of both age groups. Principal Component Analysis allowed to separate four subcomponents in the alpha range. All these subcomponents peaked at a lower frequency in children than in young adults. CONCLUSIONS: The present approaches complement and solve some of the incertitudes when the classical brain broad rhythm analysis is applied. Children have a higher absolute power than young adults for frequency ranges between 0-20 Hz, the correlation of Power Spectrum (PS) with age and the variance age comparison showed that there are six ranges of frequencies that can distinguish the level of EEG maturation in children and adults. The establishment of maturational order of different frequencies and its possible maturational interdependence would require a complete series including all the different ages.     

Copper and iron interactions with angiotensin-converting enzyme inhibitors. A study by fast-atom bombardment tandem mass spectrometry

Fast atom bombardment, combined with high-energy collision-induced tandem mass spectrometry, has been used to investigate gas-phase metal-ion interactions with captopril, enalaprilat and lisinopril, all angiotensin-converting enzyme inhibitors.Suggestions for the location of metal-binding sites are presented. For captopril, metal binding occurs most likely at both the sulphur and the nitrogen atom. For enalaprilat and lisinopril, binding preferably occurs at the amine nitrogen. Copyright 1999 John Wiley & Sons, Ltd.     

Integral equation formulation for buoyancy-driven convection problems

An integral equation formulation for buoyancy-driven convection problems is developed and illustrated. Buoyancy-driven convection in a bounded cylindrical geometry with a free surface is studied for a range of aspect ratios and Nusselt numbers. The critical Rayleigh number, the nature of the cellular motion, and the heat transfer enhancement are computed using linear theory. Green's functions are used to convert the linear problem into linear Fredholm integral equations. Theorems are proved which establish the properties of the eigenvalues and eigenfunctions of the linear integral operator which appears in these equations.     

Intracellular localization of sulfonated meso-tetraphenylporphines in a human carcinoma cell line

The intracellular localization of meso-tetraphenylporphines sulfonated to different degrees (TPPSn), in a human cervix carcinoma cell line (NHIK 3025), was studied by fluorescence microscopy and fluorescence spectroscopy. After an 18 h incubation, TPPS4, TPPS2a and TPPS2o were localized in extranuclear granules. Studies of cells stained with both TPPS4, and acridine orange, which is known to fluoresce red in lysosomes, indicated that these granules were lysosomes. In addition, a fraction of the cellbound TPPS4, TPPS2a and TPPS2o seems to be associated with the plasma membrane. Fluorescence quenching studies of cells doublestained with acridine orange and TPPS4 indicated that TPPS4 is also localized in the nucleus and in the extralysosomal cytoplasm. The intracellular location of TPPS1 differed from that of the other TPPSns studied: In 6 out of 9 experiments fluorescing extranuclear granules were found. A diffuse fluorescence extending from the perinuclear area was also observed.     

Modelling of multi-bodies in close proximity under water waves——Fluid resonance in narrow gaps

Viscous fluid model and potential flow model with and without artificial damping force(f=-μV,μ the damping coefficient and V the local averaging flow velocity) are employed in this work to investigate the phenomenon of fluid resonance in narrow gaps between multi-bodies in close proximity under water waves.The numerical results are compared with experimental data available in the literature.The comparison demonstrates that both the viscous fluid model and the potential flow model are able to predict the res...     

ERYTHROPOIETIC PROTOPORPHYRIA: PHOTODYNAMIC TRANSFER OF PROTOPORPHYRIN FROM INTACT ERYTHROCYTES TO OTHER CELLS

Erythrocytes in patients with erythropoietic protoporphyria (EPP) contain large amounts of protoporphyrin and are regarded as the main source of protoporphyrin in this disease. Cells in the skin of EPP patients accumulate protoporphyrin released from the erythrocytes and upon sun exposure endothelial cells are photodamaged. In the present study a light-induced transfer of protoporphyrin directly from EPP erythrocytes to cultured cells is demonstrated. Erythrocytes were layered upon cultured cells and irradiated. The nearness of erythrocyte and cultured cell membranes potentiated the transfer of protoporphyrin between these cells. This transfer was rapid and preceded the release of protoporphyrin to proteins in the medium. Further irradiation of the protoporphyrin-enriched cultured cells, after removal of the erythrocytes, caused severe photodamage to the cells and survival was dependent on both the amount of protoporphyrin transferred and on the light fluence. Clinical observations and the results of this study indicate that light energy may be involved in two steps in the pathophysiology of EPP: (A) light-induced release of protoporphyrin from erythrocytes to endothelial cells and (B) photodynamic damage to protoporphyrin-enriched endothelial cells.