Strabismus and postural control: a systematic review.

The primary aim of this systematic review is to evaluate how postural balance and visual system are related in cross-eyed patients. The secondary goal is to assess the benefits of eye realignment on motor skills and body balance. Analyzing two different approaches: surgical or conservative, a systematic literature search was conducted using PubMed-Medline, Google Scholar and Cochrane Central in order to identify randomized controlled trials, case series and case-control studies which contained clinical evaluation of balance in strabismic patients as well as re-evaluation after surgery or conservative treatments via posturography to evaluate surface, length and mean speed of the center of pressure (CoP). A total of 11 studies were included in this review. The MINORS score is used to assess the methodological quality of the included studies, and its mean value was 12.8 for non-comparative studies and 17.5 for comparative studies. The postural balance was lower in strabismic patients compared with the control group, with statically higher value (p < 0.05) of surface, length and mean speed of the CoP in the study group. All patients show improvement in stability after surgery, as surface, length and mean speed of the CoP decreased after surgery in all the studies with statistical significance (p < 0.05).

Amniotic membrane transplantation associated with conjunctival peritomy in the management of Mooren's ulcer: a case report.

PURPOSE: To report the association of conjunctival peritomy with amniotic membrane transplantation (AMT) at the limbus with the exclusion of the central cornea in order to preserve visual function in one case of bilateral Mooren's ulcer. METHODS: A 36-year-old man with bilateral Mooren's ulcer was unresponsive to conventional therapy. Surgical procedure was performed on his right eye, at impending risk of corneal perforation. A 20 x 20 mm piece of amniotic membrane (AM) was prepared by performing a central hole of 7.5 mm diameter with a manual trephine. A 360 degrees conjunctival peritomy was performed and the AM was placed with the epithelium side facing up and the central hole was sutured on the paracentral cornea. RESULTS: Two weeks after surgery, while the right eye showed improvement of signs and symptoms and unchanged best-corrected visual acuity (BCVA), the left eye showed a peripheral corneal perforation with prolapsed iris that required conjunctival flap. At 7 months of follow-up, the right eye showed no ocular inflammation, a reduction of the lipid-like peripheral corneal infiltrates, an increased stromal thickness, and an unchanged BCVA. The progression of corneal thinning in the left eye led the authors to perform AMT (as described) in the left eye as well. Five months after the AMT in the left eye, neither eye shows signs of disease progression, and neither requires further therapy. CONCLUSIONS: Conjunctival peritomy associated with AMT may be an alternative surgical approach in the management of Mooren's ulcers to control the inflammation and the progression of disease.

Vernal keratoconjunctivitis.

Vernal keratoconjunctivitis (VKC) is an allergic eye disease that especially affects young boys. The most common symptoms are itching, photophobia, burning, and tearing. The most common signs are giant papillae, superficial keratitis, and conjunctival hyperaemia. Patients with VKC frequently have a family or medical history of atopic diseases, such as asthma, rhinitis, and eczema. However, VKC is not associated with a positive skin test or RAST in 42-47% of patients, confirming that it is not solely an IgE-mediated disease. On the basis of challenge studies as well as immunohistochemical and mediator studies, a Th2-driven mechanism with the involvement of mast cells, eosinophils, and lymphocytes has been suggested. Th2 lymphocytes are responsible for both hyperproduction of IgE (interleukin 4, IL-4) and for differentiation and activation of mast cells (IL-3) and eosinophils (IL-5). Other studies have demonstrated the involvement of neural factors such as substance P and NGF in the pathogenesis of VKC, and the overexpression of oestrogen and progesterone receptors in the conjunctiva of VKC patients has introduced the possible involvement of sex hormones. Thus, the pathogenesis of VKC is probably multifactorial, with the interaction of the immune, nervous, and endocrine systems. The clinical management of VKC requires a swift diagnosis, correct therapy, and evaluation of the prognosis. The diagnosis is generally based on the signs and symptoms of the disease, but in difficult cases can be aided by conjunctival scraping, demonstrating the presence of infiltrating eosinophils. Therapeutic options are many, in most cases topical, and should be chosen on the basis of the severity of the disease. The most effective drugs, steroids, should however be carefully administered, and only for brief periods, to avoid secondary development of glaucoma.A 2% solution of cyclosporine in olive oil or in castor oil should be considered as an alternative. The long-term prognosis of patients is generally good; however 6% of patients develop corneal damage, cataract, or glaucoma.

Diacylglycerol mediates the thrombin-induced, protein kinase C and Ca2+ independent activation of the Na+/H+ exchanger in platelets.

Treatment of aspirinated platelets with the electroneutral K+/H+ exchanger nigericin induces a decrease in intraplatelet pH as measured with the intracellular fluorescent indicator BCECF. Under these conditions, the proton permeability of the plasma membrane is unaffected. The addition of thrombin induces a rapid partial recovery of pH(i), which is completely abolished by the Na+/H+ exchanger inhibitor NHA. The effect is also evident in the presence of the PKC inhibitors GF 109203X or staurosporine and in the absence of both external (EGTA-chelated) and internal (BAPTA-chelated) Ca2+. This makes the thrombin-induced activation of the exchanger independent of the involvement of the hitherto described activators, namely PKC and the increase in [Ca2+]i, as well of the recently reported activator arachidonic acid [Cavallini, L., Coassin, M., Borean, A., and Alexandre, A. (1996) Biochem. J. 319, 567-574], whose production requires a high [Ca2+]i. The thrombin-dependent recovery of pH(i) is prevented by the phospholipase C inhibitor ET 18 O-CH3 and is mimicked by the addition of the permeable diglyceride dioctanoyl glycerol (DiC8) exogenously supplied. The effect of thrombin and DiC8 is unaffected by inhibition of diacylglycerol lipase and diacylglycerol kinase. These experiments identify diglyceride as a novel activator of the Na+/H+ exchanger in platelets.

Arachidonic acid activates a proton conductance pathway and the Na+/H+ exchanger in platelets.

The treatment of aspirinated platelets with the endomembrane Ca(2+)-ATPase inhibitor thapsigargin (Tg) induces a large increase in cytosolic pH (pH1), as measured with the intracellular fluorescent indicator 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein. In contrast, Tg induces a decrease in pH1 in the presence of the Na+/H+ exchanger inhibitor 5-(N,N-hexamethylene)-amiloride (NHA). Both effects are inhibited if the cytosolic free Ca2+ concentration ([Ca2+]1) is chelated by loading with bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetra-acetoxymethyl ester (BAPTA-AM). Without BAPTA, the pH effects are inhibited in the presence of BSA or the phospholipase A2 inhibitor oleoyloxyethylphosphocholine. These observations are consistent with the Tg-induced pH effects being mediated at least in part by the release of arachidonic acid (ArA) on activation of phospholipase A2 by the increased [Ca2+]1. Exogenous ArA promotes a rapid decrease in pH1 in platelets suspended in a high-[Na+] medium, and an increase in pH1 if platelets are depolarized by suspension in a high-[K+] medium in the presence of valinomycin and the external pH is increased to 7.9. The protonophore carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) behaves like ArA, although ArA is not a protonophore. It is concluded that ArA activates a proton conductance across the plasma membrane. The latter is inhibited by La3+. In high-[Na+] media, the pH1 previously decreased by ArA recovers rapidly on removal of ArA with BSA. The effect is prevented by NHA. The recovery after BSA is much slower if FCCP rather than ArA is used to decrease pH1, but it is fast again with both ArA and FCCP. Furthermore, pH1 previously decreased by ArA also recovers readily on inhibition of the ArA-activated H+ conductance with La3+, and the effect is NHA-sensitive. When pH1 is decreased with the K+/H+ ionophore nigericin, a rapid recovery is activated by ArA followed by BSA (but not by BSA alone). The effect is independent of Ca2+ and protein kinase C. It is concluded that ArA, besides activating the H+ conductance, also acts as an activator of the Na+/H+ exchanger.

Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-trisphosphate receptor and promote its phosphorylation.

Prostaglandin I2 (PGI2) and sodium nitroprusside (SNP) induce a rapid decay of the thrombin-promoted increase of [Ca2+]i in aspirin-treated platelets incubated in the absence of external Ca2+. The mechanism of their effect was studied with a new method which utilizes ionomycin to increase [Ca2+]i, followed by bovine serum albumin (BSA) to remove the Ca2+ ionophore. The rapid decay of [Ca2+]i after BSA is mostly due to the reuptake into the stores, since it is strongly inhibited by the endomembrane Ca2+-ATPase inhibitor thapsigargin. PGI2 and SNP are without effect on the BSA-promoted decay both with and without thapsigargin, showing that they do not affect the activity of the Ca2+-ATPases. The fast decay of [Ca2+]i after BSA is decreased by thrombin which produces the Ca2+ releaser inositol 1,4,5-trisphosphate (InsP3), thus counteracting the activity of the endomembrane Ca2+ pump. When added after thrombin, PGI2 and SNP accelerate the BSA-activated decay of [Ca2+]i. However, under the same conditions, they do not decrease the concentration of InsP3. In saponin-permeabilized platelets, cAMP and cGMP counteract the Ca2+ release induced by exogenous InsP3. Their inhibitory effect disappears at high InsP3 concentrations. This demonstrates that PGI2 and SNP potentiate Ca2+ reuptake by inhibiting the InsP3 receptor. Two bands of approximately 260 kDa are recognized by a monoclonal antibody recognizing the C-terminal region of the InsP3 receptor. Both are phosphorylated rapidly, the heavier more intensely, in the presence of PGI2 and SNP. The phosphorylation of the InsP3 receptor is fast enough to be compatible with its involvement in the inhibition of the receptor by cyclic nucleotides.

Two classes of agonist-sensitive Ca2+ stores in platelets, as identified by their differential sensitivity to 2,5-di-(tert-butyl)-1,4-benzohydroquinone and thapsigargin.

In the absence of extracellular Ca2+, extensive Ca2+ release from the platelet intracellular stores [monitored as an increase of intracellular Ca2+ concentration ([Ca2+]i)] is produced by the combined action of the endomembrane Ca(2+)-ATPase inhibitor thapsigargin and 2 nM ionomycin. The titration of Ca2+ unloading with thapsigargin (plus ionomycin) shows that a substantial fraction of the store-associated Ca2+ is released by 8-10 nM thapsigargin, but that 100-200 nM thapsigargin is required for the complete release. The store depletion obtained in similar conditions with a different endomembrane Ca(2+)-ATPase inhibitor, 2,5-di-(tert-butyl)-1,4-benzohydroquinone (TBHQ), is always incomplete. It is completed by thrombin or by 10 nM thapsigargin. We conclude that two different types of Ca2+ pumps exist in platelets, one sensitive to TBHQ and to high thapsigargin, the other insensitive to TBHQ and sensitive to low thapsigargin. They are distributed separately in discrete subpopulations of the agonist-sensitive stores. The influx of external Ca2+ is maximal when both types of stores are Ca(2+)-depleted, either by high thapsigargin or by the combined action of low thapsigargin and TBHQ.

Antioxidant effect of manganese.

The antioxidant effects of manganese and other transition metals were studied as the inhibition of microsomal lipid peroxidation and crocin bleaching by peroxyl radicals. The peroxyl radical scavenging capacity was measured by competition kinetics analysis. While Zn(II), Ni(II), and Fe(II) were almost completely ineffective, Mn(II) and Co(II) showed a free radical scavenging capacity, exhibiting relative rate constant ratios respectively of 0.513 and 0.287. This indicates that Mn(II) is by far the most active. Therefore, the chain-breaking antioxidant capacity of Mn(II) seems to be related to the rapid quenching of peroxyl radicals according to the reaction R-OO. + Mn(II) + H(+)-->ROOH+Mn(III). The antioxidant mechanism is discussed considering the different reduction potentials of the examined cations.

Effect of hydrogen peroxide on calcium homeostasis in smooth muscle cells.

One of the major biological targets of free radical oxidations, prone, for anatomical reasons, to oxidative challenges, is the cardiovascular system. In the present paper the effect of hydrogen peroxide on intracellular ionized calcium ([Ca2+]i) homeostasis in smooth muscle cells (SMC) is studied, the major aim of the study being a better understanding of the protective effect of antioxidants and Ca2+ channel blockers. The exposure of SMC to 300 microM H2O2 induced a rapid increase of [Ca2+]i, followed by a decrease to a new constant level, higher than the basal before the oxidative challenge. When incubation medium was Ca2+ free, the pattern of [Ca2+]i change was different. The rapid increase was still observed, but it was followed by a rapid decrease to a level only slightly above the basal before the oxidative challenge. The involvement of intracellular Ca2+ stores was tested by using vasopressin, a hormone able to induce discharge of inositol 1,4,5-triphosphate-sensitive Ca2+ stores. When H2O2 was added after vasopressin no [Ca2+]i increase was observed. Treatment of cells, in which the stable increase of [Ca2+]i was induced by H2O2, with disulfide reducing compounds, induced a progressive decrease of [Ca2+]i toward the level observed before the oxidative challenge. Calcium channel blockers and antioxidants, on the other hand, effectively prevented the stabilization of [Ca2+]i at the high steady-state, after the internal Ca2+ release phase. Dihydropyridine Ca2+ channel blockers were by far more active than verapamil and among those the most active was lacidipine. Also the antioxidants trolox and N,N'-diphenyl-1,4-phenylenediamine both prevented the [Ca2+]i unbalance. These results suggest that Ca+ channel blockers and antioxidants, although inactive on oxidative stress-induced Ca2+ release from intracellular stores, prevent the increased influx apparently related to a membrane thiol oxidation.

Enzymatic recycling of oxidized ascorbate in pig heart: one-electron vs two-electron pathway.

Enzymatic systems able to reduce either dehydroascorbate or ascorbyl radical back to ascorbate by "recycling" vitamin C may contribute to lowering the nutritional requirement of it and to increase tissue antioxidant capacity. The activities of two enzymatic activities, GSH-dehydroascorbate reductase (two-electron reduction pathway) and NADH-semidehydroascorbate reductase (one-electron reduction pathway) in pig tissues, have been investigated. The activity of glutathione-dependent reduction of dehydroascorbate, although measurable, appeared negligible taking into consideration the low physiological substrate concentration. On the other hand, the one-electron reduction of ascorbyl radical resulted fast enough to slow down the consumption of the antioxidant vitamin.

Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase.

The role of vitamin E in the protection against iron dependent lipid peroxidation was studied in rat liver microsomes and Triton-dispersed microsomal lipid micelles. In these systems, an antioxidant effect of vitamin E at a physiological ratio to phospholipids could be observed only in the presence of phospholipid hydroperoxide glutathione peroxidase (PHGPX) and glutathione. The rationale of this cooperation is discussed on the basis of the hydroperoxyl radical scavenging capacity of vitamin E and the reduction of membrane hydroperoxides by PHGPX. The scavenging of lipid hydroperoxyl radicals by vitamin E, although inhibiting propagation of the peroxidative chain, produces lipid hydroperoxides from which ferrous iron generates alkoxyl radicals that react with vitamin E almost as fast as with fatty acids. Therefore, only if membrane hydroperoxides are continuously reduced by this specific peroxidase does the scavenging of hydroperoxyl radicals by vitamin E lead to an effective inhibition of lipid peroxidation.

Increased ultra weak chemiluminescence emission from rat heart at postischemic reoxygenation: protective role of vitamin E.

Aim of this study was to confirm an increased free radical generation rate during ischemia-reoxygenation, by ultra-weak chemiluminescence detection at the surface of perfused rat heart. We observed that reoxygenation following 30 min global ischemia, induces an increase of ultraweak chemiluminescence emission in isolated perfused heart only if partial depletion of vitamin E is induced by dietary manipulation. Moreover, in normal diet fed rats, vitamin E is partially consumed during global ischemia, but not during reoxygenation. Since chemiluminescence increases during post-ischemic reperfusion, when vitamin E myocardial content is lowered, the most probable free radicals involved are the hydroperoxyl radical derivatives of lipids. These radicals, indeed, are known both to produce photoemission by disproportion and to react with vitamin E. On the other hand, the nature of the reaction that consumes vitamin E during ischemia is still obscure. Accordingly, the basal level of vitamin E myocardial content seems to be a key factor for protecting the heart against reoxygenation injury and its consumption during ischemia could be a determinant of myocardial sensitivity to oxidative stress during reperfusion.

Antioxidant defences of rabbit alveolar lining fluid.

In the lower respiratory tract, alveolar cells are exposed to an oxidative challenge related to the exposure to both high levels of molecular oxygen and oxidants generated by activated phagocytes. The antioxidant defence system of alveolar cells has been thoroughly investigated, but some reports also suggest the presence of antioxidants in the layer of fluid lining the alveoli. In this report we present our studies on the antioxidant activities present in the bronchoalveolar lavage of adult rabbits. We studied total radical-trapping antioxidant capacity of surfactant and the activity of antiperoxidant enzymes. Although previous reports suggested the presence of radical scavengers, we did not find any antioxidant activity in purified surfactant. On the other hand the alveolar-lining fluid seems to contain superoxide dismutase, catalase and glutathione peroxidase, but not appreciable amounts of ferroxidase activity, as previously suggested. These enzymes could protect alveolar cells by catalyzing the dismutation of superoxide and hydrogen peroxide. The presence of glutathione peroxidase in the alveolar space seems to be physiologically relevant since the alveolar lining fluid also contains millimolar amounts of glutathione. Our studies support the concept that the alveolar lining fluid contains an active defence system against products of partial reduction of oxygen, but not chain-breaker antioxidants.

Kinetic mechanism and substrate specificity of glutathione peroxidase activity of ebselen (PZ51).

The glutathione peroxidase activity of ebselen (PZ51) was studied using different hydroperoxidic substrates. The single progression curves obtained in the spectrophotometric test were processed by a computer to fit the integrated rate equation that describes the ping pong reaction of the Se glutathione peroxidase. Ebselen catalyzes the GSH peroxidase reaction with a mechanism that appears kinetically identical to the mechanism of the enzymes. The inactivation of the catalytic properties of ebselen by iodoacetate suggests that a selenol moiety is involved. Among the substrates tested, the best hydroperoxidic substrates are the hydroperoxy derivatives of phosphatidyl choline. Ebselen is active also on membrane hydroperoxides as does phospholipid hydroperoxide glutathione peroxidase but not glutathione peroxidase.

Modification of the xanthine-converting enzyme of perfused rat heart during ischemia and oxidative stress.

The reversible and irreversible conversion of xanthine dehydrogenase to xanthine oxidase during ischemia/reperfusion and oxidative stress induced by hydrogen peroxide or diamide and its relationship with glutathione and protein SH groups were studied. The direct spectrophotometric measurement of the various forms of the xanthine-converting enzyme indicates that, in the fresh rat heart or after normoxic perfusion, there always is a basal level of 80% xanthine dehydrogenase and 20% of xanthine oxidase (15% irreversible and 5% reversible) that could contribute to the background production of free radicals. There is no significant increase of irreversible xanthine oxidase during ischemia nor during reperfusion. After global ischemia the reversible oxidase shows almost no increase while, when ischemia is followed by reperfusion, there is a limited increase (less then 9%) of the reversible xanthine oxidase. In the latter conditions there is a decrease of glutathione and of SH groups of about 70% and 25%, respectively. Perfusion for 1 h with oxidizing agents like hydrogen peroxide (60 microM) or diamide (100 microM) determines a marked conversion of xanthine dehydrogenase to reversible xanthine oxidase of about 40% and 60%, respectively; this oxidase activity partially reconverts to the dehydrogenase after withdrawing the oxidizing agents from the perfusion medium. The level of irreversible xanthine oxidase remains unchanged in all the conditions tested. Both hydrogen peroxide and diamide induce a strong decrease in SH groups and depletion of glutathione. The xanthine dehydrogenase----xanthine oxidase conversion thus appears to be sensitive to the redox state of thiol groups.