AMPA glutamate receptors mediate the antidepressant-like effects of N-acetylcysteine in the mouse tail suspension test.

The aim of this study was to investigate the involvement of noradrenaline, serotonin, and subtypes of glutamate receptors in the antidepressant-like effects of N-acetylcysteine (NAC). The tail suspension test was used with male CF1 albino mice. D,L-α-methyl-ρ-tyrosine and ρ-chlorophenylalanine methyl ester hydrochloride were used as synthesis inhibitors of noradrenaline and serotonin, respectively. N-methyl-D-aspartate (NMDA) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione were used as an NMDA receptor agonist and an α-amino acid-3-hydroxy-5-methyl-4-isoxazol propionic acid (AMPA) receptor antagonist, respectively. NAC (10, 25, and 50 mg/kg intraperitoneally) significantly (P<0.05) decreased tail suspension test immobility time, whereas pretreatment with D,L-α-methyl-ρ-tyrosine, ρ-chlorophenylalanine methyl ester hydrochloride, and NMDA partially prevented (P<0.05) the effects of NAC (25 mg/kg), and pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione completely abolished (P<0.01) this effect. The study corroborates the antidepressant-like effects of NAC in the TST, a model with a well-established predictive value. The results point to the key role of AMPA receptors in the mechanism of the antidepressant-like action of NAC. Like other AMPA potentiators, NAC indirectly modulates noradrenaline and serotonin pathways. It is suggested that the value of NAC as an antidepressant arises from combined and intertwined effects on a variety of pathways.

Bioreactive self-assembled monolayers on hydrogen-passivated Si(111) as a new class of atomically flat substrates for biological scanning probe microscopy.

This is the first report of bioreactive self-assembled monolayers, covalently bound to atomically flat silicon surfaces and capable of binding biomolecules for investigation by scanning probe microscopy and other surface-related assays and sensing devices. These monolayers are stable under a wide range of conditions and allow tailor-made functionalization for many purposes. We describe the substrate preparation and present an STM and SFM characterization, partly performed with multiwalled carbon nanotubes as tapping-mode supertips. Furthermore, we present two strategies of introducing in situ reactive headgroup functionalities. One method entails a free radical chlorosulfonation process with subsequent sulfonamide formation. A second method employs singlet carbenemediated hydrogen-carbon insertion of a heterobifunctional, amino-reactive trifluoromethyl-diazirinyl crosslinker. We believe that this new substrate is advantageous to others, because it (i) is atomically flat over large areas and can be prepared in a few hours with standard equipment, (ii) is stable under most conditions, (iii) can be modified to adjust a certain degree of reactivity and hydrophobicity, which allows physical adsorption or covalent crosslinking of the biological specimen, (iv) builds the bridge between semiconductor microfabrication and organic/biological molecular systems, and (v) is accessible to nanopatterning and applications requiring conductive substrates.

Treatment of alopecia areata with squaric acid dibutylester.

BACKGROUND: Among contact allergens that are frequently used in the treatment of alopecia areata (AA), squaric acid dibutylester (SADBE) stands out for its good tolerability and its mild side effects. METHODS: One hundred and forty-four patients with AA of varying degrees were treated with SADBE. Of these, 71 had AA affecting less than 50% of the scalp, and 73 had a severe form, including 13 patients with alopecia totalis (AT) and two with alopecia universalis (AU). The patients were treated using both traditional and nontraditional methods. RESULTS: In the less severe form, we obtained a 80% rate of regrowth, compared to the 49% of the more severe form including 13 cases of AT and the two of AU. The failure rate was higher for patients with the more severe form (29%) compared to a 7% rate only for patients with mild AA. We also observed four cases of initial regrowth on the side of the scalp opposite to the site of application ('castling phenomenon'). Among those patients who were treated with application of SADBE on the right side of the back, three displayed regrowth on the left side of the scalp, (i.e., on the opposite side) and in an area distant from the site of application; for two patients the regrowth began on the right side of the scalp and one of them also displayed growth of fine hairs in the right dorsal region, the site of application of the compound. CONCLUSIONS: Our data further support the hypothesis of a systemic action of SADBE; however, further confirmation on a larger sample of cases is needed.