Thrombocytopenia caused by platelet consumption in thrombi is a major manifestation of hemolytic uremic syndrome (HUS) associated with Shiga toxin (Stx) producing Escherichia coli. Platelets have glycosphingolipid receptors capable of binding Stx, but a direct interaction between the toxin and platelets, leading to platelet activation, has not been reported. In this study, it is shown that Stx1 and its B (binding) subunit (Stx1B), at 10 pg/mL to 10 ng/mL, bound to platelets. IntroductionShiga toxin (Stx)-producing Escherichia coli (STEC) have been associated with cases of hemolytic uremic syndrome (HUS). Microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia characterize this syndrome. Stx has been specifically implicated as a causal factor 1 of HUS because cases of the disease have been associated with Stx-producing strains, 2 the toxin has been identified in the kidney of a patient with HUS, 3 and the toxin has been found to be cytotoxic for renal endothelial and epithelial cells. [4][5][6][7][8] In addition, animal models have reproduced aspects of HUS using wild-type bacteria that produce the toxin 9,10 or purified toxin. 11 The toxin is composed of 5 B, or binding, subunits and 1 enzymatically active A subunit. 12 The molecular weight of the A subunit is 33 000 kd, and that of the pentameric B subunit is approximately 35 000 kd. 13 The B subunit (StxB) binds to a glycosphingolipid receptor on cell membranes, globotriaosyl ceramide (Gb3), containing the terminal disaccharide galactose ␣(1-4) galactose ␤. 14 A recent study showed that Stx could bind to platelets through Gb3 and a novel platelet glycosphingolipid termed band 0.03. 15 Other studies have not been able to reproduce these results. 16,17 Binding to the cell mediates endocytosis of the holotoxin. Intracellularly the A subunit is proteolytically nicked, binds to 60S ribosomes, and thereby inhibits protein synthesis leading to cell death. 18 Thrombocytopenia is an important feature of HUS. Platelets are consumed in small thrombi, and these thrombi may compromise the blood supply to various organs, particularly the kidney. The mechanism by which these thrombi are formed is unclear, and platelet activation has been suggested. Studies performed on platelets from patients with HUS showed impaired aggregating responses 19,20 and reduced ␤-thromboglobulin (␤-TG) content. 19 Platelet-derived products such as ␤-TG, platelet factor 4, 21 and soluble P-selectin 22 were found to be elevated during acute HUS. Furthermore, changes in platelet ultramorphology were noted. 23 Increased platelet-derived microvesicles were found in these patients, 24 indicating platelet activation. Plasma from patients with HUS increased aggregation of normal platelets, but the factor causing this was not determined. 25 Several previous studies have investigated a direct interaction between Stx and platelets. Culture filtrates from Stx-producing E coli were found to induce platelet-aggregating activity, 26 but purified Stx did not increase platelet aggregation 16...

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This complication has not been reported previously and may be an individual hypersensitivity reaction to the riboflavin or UVA light in the anterior stroma.

. Purpose:  To study the effect of intravitreal (IVT) ranibizumab on the retinal arteriolar diameter in patients with neovascular age‐related macular degeneration (AMD). Methods:  Ten eyes of 10 patients with previously untreated neovascular AMD were included. All eyes had three monthly IVT injections of ranibizumab and then were retreated as needed, based on visual acuity and optical coherence tomography (OCT) criteria. The diameter of the retinal arterioles was measured in vivo with a retinal vessel analyser (RVA) before the first IVT injection, 7 and 30 days after the first, the second and the third injection, and at month 12 of follow‐up. Results:  A significant vasoconstriction of the retinal arterioles was observed following each one of the first three IVT injections of ranibizumab. Thirty days following the first, second and third injection, there was a mean decrease of 8.4 ± 3.2%, 11.9 ± 4.5% and 18.5 ± 7.2%, respectively, of the retinal arteriolar diameter compared with baseline (p < 0.01). At month 12, the vasoconstriction was still present with a mean decrease of 19.1 ± 8.3% of the retinal arteriolar diameter compared with baseline (p < 0.01). Median number of ranibizumab injections was 4 (range 3–10). There was no correlation between the number of injections and percentage diameter decrease at month 12 (r = −0.54, p > 0.1). There was no significant change in mean arterial pressure (MAP) during the period of follow‐up (p > 0.05). Conclusions:  These results suggest that IVT ranibizumab induces sustained retinal arteriolar vasoconstriction in eyes with neovascular AMD.

Panretinal photocoagulation has a vasoconstrictive effect on retinal arterioles in patients with severe nonproliferative or proliferative diabetic retinopathy. These results are consistent with an autoregulatory response of the retinal circulation to increased inner retinal oxygen tension after PRP. The retinal vessel analyzer is a fast, accurate, noninvasive, online measuring system for the study of the retinal vascular response to PRP in patients with diabetic retinopathy.