Visible light-absorbing cationic water-soluble gallium(III) phthalocyanines (GaPcs) peripherally substituted with four and eight methylpyridyloxy groups were synthesized and investigated as antimicrobial photodynamic sensitizers. The inserted large gallium ion in the phthalocyanine ligand is axially substituted by one hydroxyl group which prevents aggregation of the complexes in aqueous solution. The cellular uptake and the photodynamic activity for the representative strains of the Gram positive bacteria methicillin-resistant Staphylococcus aureus(MRSA) and Enterococcus faecalis, of the Gram negative bacterium Pseudomonas aeruginosa and of the fungus Candida albicans in planktonic phase were studied. The tetra-methylpyridyloxy substituted GaPc1 showed lower cellular uptake compared to the octa-methylpyridyloxy substituted GaPc2. The photodynamic activity of the GaPcs was studied in comparison to methylene blue (MB) and a photodynamically active Zn(II)-phthalocyanine with the same substitution (ZnPcMe). Photodynamic treatment with 3.0 μM GaPc1 at mild light conditions (50 J cm(-2), 60 mW cm(-2)) resulted in a high photoinactivation of the microorganisms in the planktonic phase nevertheless the dark toxicity of GaPc1 towards MRSA and E. faecalis. GaPcs against fungal biofilm grown on polymethylmethacrylate (PMMC) resin showed a complete inactivation at a higher concentration of GaPc2 (6.0 μM) and of the referent sensitizer ZnPcMe. However, the bacterial biofilms were not susceptible to treatment of GaPcs with only 1-2 log reduction of the biofilm. The bacterial biofilm E. faecalis was effectively inactivated only with MB. The water-soluble octa-methylpyridyloxy substituted GaPc2 has a potential value for photodynamic treatment of C. albicans biofilms formed on denture acrylic resin.
Dopamine is the most abundant catecholamine in the vertebrate retina. Despite the description of retinal dopaminergic cells three decades ago, many aspects of their function in the retina remain unclear. There is no consensus among the authors about the stimulus conditions for dopamine release (darkness, steady or flickering light) as well as about its action upon the various types of retinal cells. Many contradictory results exist concerning the dopamine effect on the gross electrical activity of the retina [reflected in electroretinogram (ERG)] and the receptors involved in its action. This review summarized current knowledge about the types of the dopaminergic neurons and receptors in the retina as well as the effects of dopamine receptor agonists and antagonists on the light responses of photoreceptors, horizontal and bipolar cells in both nonmammalian and mammalian retina. Special focus of interest concerns their effects upon the diffuse ERG as a useful tool for assessment of the overall function of the distal retina. An attempt is made to reveal some differences between the dopamine actions upon the activity of the ON versus OFF channel in the distal retina. The author has included her own results demonstrating such differences.
The expression of GABA receptors (GABARs) was studied in frog and turtle retinae. Using immunocytochemical methods, GABA(A)Rs and GABA(C)Rs were preferentially localized to the inner plexiform layer (IPL). Label in the IPL was punctate indicating a synaptic clustering of GABARs. Distinct, but weaker label was also present in the outer plexiform layer. GABA(A)R and GABA(C)R mediated effects were studied by recording electroretinograms (ERGs) and by the application of specific antagonists. Bicuculline, the GABA(A)R antagonist, produced a significant increase of the ERG. Picrotoxin, when co-applied with saturating doses of bicuculline, caused a further increase of the ERG due to blocking of GABA(C)Rs. The putative GABA(C)R antagonist Imidazole-4-acidic acid (I4AA) failed to antagonize GABA(C)R mediated inhibition and, in contrast, appeared rather as an agonist of GABARs.
We assessed the contribution of GABAa and GABAc receptors to GABAergic effects on b- and d-wave in frog ERG in a wide range of light stimulation conditions. The amplitude of both b- and d-wave was increased during GABAa receptor blockade by bicuculline as well as during additional GABAc receptor blockade by picrotoxin. The effects of GABAa receptor blockade were more pronounced in light adaptation conditions. They strongly depended on stimulus intensity and showed considerable ON/OFF-response asymmetry. The effects of GABAc receptor blockade were more pronounced in dark adaptation conditions. They didn't vary much with stimulus intensity and showed little ON/OFF-response asymmetry.
In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells in distal retina. The activity of large populations of ON and OFF bipolar cells is reflected in the b- and d-waves of the diffuse electroretinogram (ERG). The role of gamma-aminobutyric acid (GABA), acting through ionotropic GABA receptors in shaping the ON and OFF responses in distal retina, is a matter of debate. This review summarized current knowledge about the types of the GABAergic neurons and ionotropic GABA receptors in the retina as well as the effects of GABA and specific GABAA and GABAC receptor antagonists on the activity of the ON and OFF bipolar cells in both nonmammalian and mammalian retina. Special emphasis is put on the effects on b- and d-waves of the ERG as a useful tool for assessment of the overall function of distal retinal ON and OFF channels. The role of GABAergic system in establishing the ON-OFF asymmetry concerning the time course and absolute and relative sensitivity of the ERG responses under different conditions of light adaptation in amphibian retina is also discussed.
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