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BACKGROUND: Erythrocyte deformability is impaired in sickle cell disease (SCD). The regulation of cytoskeletal protein organization plays a key role in erythrocyte deformability. The activation of adenylyl cyclase (AC)/cAMP/Protein kinase A (PKA) signaling pathway was associated with increased deformability in healthy erythrocytes, however the role of this pathway in SCD is unknown. OBJECTIVE: We evaluated mechanical responses of sickle red blood cells under physiological levels of shear stress and the possible link between their deformability and AC/cAMP/PKA signaling pathway. METHODS: The shearing of sickle red blood cells at physiological level (5 Pa) and the measurement of deformability were performed by a laser assisted optical rotational cell analyzer (LORRCA). RESULTS: Red blood cell deformability increased of 2.5-6.5% by blocking the activity of phosphodiesterase with Pentoxifylline (10 M) (p < 0.05). The inhibition of AC with SQ22536 (100 M) produced more significant rise in deformability (+4.8-12%, p < 0.01). No significant change was observed by the inhibition of PKA with H89 (10 M). CONCLUSION: Pentoxifylline and SQ22536 increased the deformability of sickle red blood cells under fluid shear stress. Modulation of the AC/cAMP/PKA pathway could have the potential to be an effective therapeutic approach for SCD through shear-induced improvements of RBC deformability.

Purpose: To evaluate the 36 months changes in posterior corneal surface parameters in keratoconic eyes after accelerated corneal cross-linking and to compare the data with uncross-linked progressive and non-progressive keratoconic eyes. Methods: Thirty five cross-linked, 30 uncross-linked progressive, and 30 uncross-linked non-progressive keratoconic eyes were included. Maximum keratometry (Kmax), thinnest pachymetry, minimum radius of curvature back (Rminback), asphericity back, posterior elevation and corneal densitometry, back corneal higher order aberrations (HOAs), back surface deviation (Db), final D, posterior radius of curvature (PRC) and ‘B’ unit values were recorded at baseline and at the 12, 24, 36 months follow-up. Data were analyzed with repeated measures ANOVA and paired t-tests.Results: Kmax and thinnest pachymetry were significantly changed in the cross-linked and progressive uncross-linked groups. Rminback, asphericity back, and HOAs did not change in either group. Total posterior corneal densitometry improved; posterior elevation, Db and B unit worsened in the cross-linked group and did not change in the uncross-linked groups. PRC and final D worsened in the cross-linked and progressive uncross-linked groups, and did not change in the non-progressive group. Conclusion: Despite a decreased Kmax, the posterior corneal surface parameters, posterior elevation values were determined to have significantly worsened in the cross-linked group and this increase was higher than in progressive uncross-linked eyes.

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