Recent Advances in Malaria Chemotherapy

A short review of the currently used antimalarial drugs is reported. The molecular aspects of the different possible mechanisms of action of artemisinin is documented, including recent data on heme alkylation. The preparation and the in vitro antimalarial activity of new modular molecules named “trioxaquines” is also presented.     

Review of the basic methods for characterizing integrated-optic waveguides

This article presents a short review of the various methods of characterizing integrated-optic waveguides. It is intended to acquaint researchers, particularly beginners in this field, with the principles of some of the widely used techniques of characterizing one-dimensional (planar) and two-dimensional (such as channel or rib) waueguides.     

Beam-propagation method based on the Wigner transform: a new formulation

A new formulation of the classical scalar beam-propagation method is derived by use of the Wigner transform. The new method is faster than the classical beam-propagation method because no Fourier transform must be computed. An example given to illustrate the proposed method shows additional advantages.     

Porphyrin-aminoquinoline conjugates as telomerase inhibitors

A series of metalloporphyrins was prepared in order to target the G-quadruplex structure of telomeric DNA for the design of antitelomerase compounds. The initial cationic tetramethylpyridiniumyl porphyrin was modified by the replacement of one or two methylpyridiniumyl groups by one or two 4-aminoquinoline moieties, at the meso position, in order to increase the cell penetration and the quadruplex affinity. The porphyrins were either metallated by manganese or by nickel. The degradation of quadruplex DNA was assayed in vitro with the manganese redox-active derivatives. All porphyrins complexes were capable of inhibiting the telomerase enzyme with IC50 values in the micromolar range (TRAP assay).     

Molecular responses to stress induced in normal human caucasian melanocytes in culture by exposure to simulated solar UV

Melanocytes play a central role in the response of skin to sunlight exposure. They are directly involved in UV-induced pigmentation as a defense mechanism. However, their alteration can lead to melanoma, a process where the role of sun overexposure is highly probable. The transformation process whereby UV damage may result in melanoma initiation is poorly understood, especially in terms of UV-induced genotoxicity in pigmented cells, where melanin can act either as a sunscreen or as a photosensitizer. The aim of this study was to analyze the behavior of melanocytes from fair skin under irradiation mimicking environmental sunlight in terms of spectral power distribution. To do this, normal human Caucasian melanocytes in culture were exposed to simulated solar UV (SSUV, 300-400 nm). Even at relatively high doses (until 20 min exposure, corresponding to 12 kJ/m2 UV-B and 110 kJ/m2 UV-A), cell death was limited, as shown by cell viability and low occurrence of apoptosis (caspase-3 activation). Moreover, p53 accumulation was three times lower in melanocytes than in unpigmented cells such as fibroblasts after SSUV exposure. However, an important fraction of melanocyte population was arrested in G2-M phase, and this correlated well with a high induction level of the gene GADD45, 4 h after exposure. Among the genes involved in DNA repair, gene XPC was the most inducible because its expression increased more than two-fold 15 h after a 20 min exposure, whereas expression of P48 was only slightly increased. In addition, an early induction of Heme Oxygenase 1 (HO1) gene, a typical response to oxidative stress, was also observed for the first time in melanocytes. Interestingly, this induction remained significant when melanocytes were exposed to UV-A radiation only (320-400 nm), and stimulation of melanogenesis before irradiation further increased HO1 induction. These results were obtained with normal human cells after exposure to SSUV radiation, which mimicked natural sunlight. They provide new data related to gene expression and suggest that melanin in light skin could contribute to sunlight-induced genotoxicity and maybe to melanocyte transformation.     

Immobilization as a tool for the stabilization of lignin peroxidase produced byPhanerochaete chrysosporium INA-12

Lignin peroxidase immobilization was achieved by covalent coupling on CNBr-Sepharose 4B. Protein immobilization yield was around 80%. For veratryl alcohol oxidation, in the presence of hydrogen peroxide, both soluble and bound enzymes exhibited the same pH profile with an optimum near 2.5. Catalytic parameters (kc andK _m ) were seriously affected by immobilization. On the other hand, immobilization provided a noticeable stabilization of the enzyme against acidic pH and high temperatures. A 15–20 increase in the half-inactivation times at pH 2.2 and 2.7, respectively, could be observed. Bound enzyme was also much more thermostable than soluble.