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After damage to the central nervous system (CNS) the body is protected by an adaptive immune response which is directed against myelin-associated proteins. Active immunization with nonpathogenic derivatives of CNS-associated peptides (DCAP) reduces the degeneration of neurons and promotes motor recovery after spinal cord injury (SCI) in rats. In order to improve even more the neurological outcome obtained with this therapy, either a combination of DCAP immunization plus glutathione monoethyl ester (GSHE) or a double DCAP immunization were performed. GSHE is a cell-permeant derivative of glutathione, a potent antioxidant agent that significantly inhibits lipid peroxidation after SCI. After a contusive or compressive SCI, the combination of GSHE + DCAP immunization, induced better motor recovery, a higher number of myelinated axons and better rubrospinal neuron survival than immunization alone. On the other hand, double-DCAP immunization counteracted the protective effect of DCAP therapy. Motor recovery and neuronal survival of double-immunized rats were similar to those observed in control animals (PBS-treated). Further studies revealed that double immunization was not encephalitogenic but inhibited the proliferative response of T-cells specific to the DCAP-immunized peptide. This clonal dysfunction was probably secondary to anergy. GSHE improves the protective effect induced by DCAP immunization while double immunization, reverts it.

1 The aim of the present study was to determine the eect of nitric oxide (NO) on angiotensinconverting enzyme (ACE) activity. 2 A biochemical study was performed in order to analyse the eect of the NO-donors, SIN-1 and diethylamine/NO (DEA/NO), and of an aqueous solution of nitric oxide on the ACE activity in plasma from 3-month old male Sprague-Dawley rats and on ACE puri®ed from rabbit lung. SIN-1 signi®cantly inhibited the activity of both enzymes in a concentration-dependent way between 1 and 100 mM. DEA/ NO inhibited the activity of puri®ed ACE from 0.1 mM to 10 mM and plasma ACE, with a lower potency, between 1 and 100 mM. An aqueous solution of NO (100 and 150 mM) also inhibited signi®cantly the activity of both enzymes. Lineweaver-Burk plots indicated an apparent competitive inhibition of HipHis-Leu hydrolysis by NO-donors. 3 Modulation of ACE activity by NO was also assessed in the rat carotid artery by comparing contractions elicited by angiotensin I (AI) and AII. Concentration-response curves to both peptides were performed in arteries with endothelium in the presence of the guanylyl cyclase inhibitor, ODQ (10 mM), and the inhibitor of NO formation, L-NAME (0.1 mM). NO, which is still released from endothelium in the presence of 10 mM ODQ, elicited a signi®cant inhibition of AI contractions at low concentrations (1 and 5 nM). In the absence of endothelium, 1 mM SIN-1 plus 10 mM ODQ, as well as 10 mM DEA/NO plus 10 mM ODQ induced a signi®cant inhibition on AI-induced contractions at 1 and 5 nM and at 1 ± 100 nM, respectively. 4 In conclusion, we demonstrated that (i) NO and NO-releasing compounds inhibit ACE activity in a concentration-dependent and competitive way and that (ii) NO release from endothelium physiologically reduces conversion of AI to AII.

Like other tissues of the central nervous system, the retina is susceptible to damage by oxidative processes that result in several neurodegenerative disease such as age-related macular degeneration, diabetic retinopathy, glaucoma, ischaemic retinal disease, retinal disease produced by light oxidation, and detached retina, among other diseases. The use of antioxidant substances is a solution to some health problems caused by oxidative stress, because they regulate redox homeostasis and reduce oxidative stress. This is important for neurodegeneration linked to oxidation processes. In line with this, Ginkgo biloba is a medicinal plant with excellent antioxidant properties whose effects have been demonstrated in several degenerative processes, including retinal diseases associated with neurodegeneration. This review describes the current literature on the role of ginkgo in retinal diseases associated with neurodegeneration. The information leads to the conclusion that G. biloba extracts might be a good option to improve certain neurodegenerative retinal diseases, but more research is needed to determine the safety and efficacy of G. biloba in these retinal degenerative processes.