Acute neurological visual loss in young adults: causes, diagnosis and management.

Visual loss in the young adult can be caused by demyelinating diseases, inflammatory and autoimmune processes, infections, ischaemic events, and compressive lesions of the optic nerve. Diagnosis of the aetiologies of visual loss is reached by combining data from radiological studies, electrophysiological tests, and blood and cerebrospinal fluid analysis. Treatment is primarily aimed at decreasing the insult on the optic nerve and eventually controlling the primary disorder. The literature discusses separately the different aetiologies of visual loss. We present a review of the clinical characteristics of visual loss in the young adult, the different diagnostic measures, and the latest therapeutic strategies. The aim of this work is to summarise this entity in a practical way to guide clinicians in the diagnosis and management of this disorder.

Cyclic nucleotides augment the phasic action of tetraethylammonium on guinea-pig trachealis.

It is known that after exposure to (3 mM) tetraethylammonium (TEA), guinea-pig isolated trachealis generates tonic spasm followed by phasic tension changes. We found that 8-Br-cAMP or 8-Br-cGMP (10(-6)-5 x 10(-4) M) suppressed tonic spasm secondary to TEA and induced rapid mechanical oscillations. NaN3, forskolin, aminophylline, and isoprenaline had effects similar to those of the cyclic nucleotides. Tetrodotoxin, atropine, diphenhydramine, and cimetidine were without effect on the rapid oscillations. KCl (16 mM) stimulated the oscillations in tissue treated with TEA or TEA plus 8-Br-cGMP. Diltiazem abolished all rhythmic activity in TEA plus 8-Br-cGMP-treated tissues. We conclude: (A) The rapid oscillations are a result of increased cytoplasmic calcium flux with K+ affecting the contractile arm by increasing Ca2+ entry and cyclic nucleotides affecting the relaxant arm by reducing cytosolic free Ca2+. (B) The cyclic nucleotide effect is direct. (C) Cyclic nucleotides may enhance the rate of contraction and relaxation in the presence of some forms of phasic activity.

The role of mitochondrial matrix enzymes in the metabolism and toxicity of cysteine conjugates.

The submitochondrial localization and identity of enzymes which metabolize cysteine conjugates were investigated. Glutamine transaminase K was purified from rat kidney mitochondrial soluble fraction and was shown to be a cysteine conjugate beta-lyase. The purified mitochondrial enzyme is similar to the cytosolic glutamine transaminase K whose beta-lyase activity with S-(1,2-dichlorovinyl)-L-cysteine (DCVC) is regulated by concurrent transamination (Stevens, J. L., Robbins, J. D., and Byrd, R. A. (1986) J. Biol. Chem. 261, 15529-15537). However, beta-lyase activity in whole mitochondria is largely independent of regulation by cosubstrates for transamination suggesting that factors present in mitochondria are able to support the beta-lyase activity in the absence of added alpha-keto acid. Fractionation of mitochondria results in a loss of the independent beta-lyase activity. However, the majority of the beta-lyase activity can be recovered in the matrix if it is stimulated by the addition of alpha-keto-gamma-methiolbutyrate. The data suggest that the regulation of beta-elimination by the competing transamination pathway is different for each substrate and that multiple beta-lyases may exist in rat kidney. S-(2-Benzothiazolyl)-L-cysteine (BTC) is a poor substrate for purified glutamine transaminase K from mitochondria and cytosol, but BTC is as active as DCVC in crude mitochondrial matrix suggesting that other enzymes may be present. In contrast to DCVC, with BTC as substrate, the beta-lyase activity of the purified enzyme and enzyme(s) in the mitochondrial matrix is largely alpha-keto acid-independent. The existence of multiple enzymes is also supported by the observation that alpha-keto acids which are not substrates for purified glutamine transaminase K from mitochondria and cytosol do stimulate beta-lyase activity in the mitochondrial matrix fraction. Mitoplasts were found to be sensitive to DCVC toxicity consistent with the matrix localization of beta-lyase activity. The possible role in cysteine conjugate toxicity of matrix enzyme regulation by alpha-keto acids is discussed.