Solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine for enhanced bioavailability of highly lipophilic bioactive carotenoid lutein

The objectives of this study was to prepare solid self-nanoemulsifying drug delivery system (S-SNEDDS) containing phosphatidylcholine (PC), an endogenous phospholipid with excellent in vivo solubilization capacity, as oil phase for the delivery of bioactive carotenoid lutein, by spray drying the SNEDDS (liquid system) containing PC using colloidal silica (Aerosil® 200 VV Pharma) as the inert solid carrier, and to evaluate the enhanced bioavailability (BA) of lutein from S-SNEDDS. The droplet size analyses revealed droplet size of less than 100 nm. The solid state characterization of S-SNEDDS by SEM, DSC, and XRPD revealed the absence of crystalline lutein in the S-SNEDDS. The bioavailability study performed in rabbits resulted in enhanced values of C_max and AUC for S-SNEDDS. The enhancement of C_max for S-SNEDDS was about 21-folds and 8-folds compared with lutein powder (LP) and commercial product (CP), respectively. The relative BA of S-SNEDDS compared with CP or LP was 2.74-folds or 11.79-folds, respectively. These results demonstrated excellent ability of S-SNEDDS containing PC as oil phase to enhance the BA of lutein in rabbits. Thus, S-SNEDDS containing PC as oil phase could be a useful lipid drug delivery system for enhancing the BA of lutein in vivo.     

Left Ventricular Lateral Annulus and Left Atrial Free‐Wall Velocity Time Integral Indicate Thromboembolism in Patients with Rheumatic Atrial Fibrillation

Background: Low wall motion and stasis increase the likelihood of clot formation. We hypothesized that tissue Doppler indices of left atrial (LA) motion are reduced in the presence of LA thrombi and may be predictive for clot formation in patients with atrial fibrillation (AF). Methods: We did an observational study for 3 years in 118 patients with rheumatic mitral valve disease in chronic AF who had not received anticoagulation, with (Group 1, n = 36) and without (Group 2, n = 82) thromboembolism. Pulsed tissue Doppler systolic velocities and velocity time integrals (VTIs) were measured in all four chambers. A mean LA VTI was calculated. LA strain during ventricular systole was calculated using VTI and distance between two LA locations. Results: Logistic regression analysis showed that, after adjusting for age, gender, diabetes, hypertension, LA size, and left ventricular (LV) ejection fraction, mean LA VTI [Odds ratio (OR) 0.69, 95%CI (0.56–0.86, P = 0.03)] and lateral mitral annulus VTI [OR 0.15 (0.04–0.56, P = 0.03)] were associated with clot formation. The addition of these two parameters to the conventional risk factors increased the ability to predict thromboembolism (Nagelkerke R²= 0.32–0.50, P = 0.01; area under the curve 0.83 by receiver operating characteristic analysis, P = 0.01). LA strain also had potential to indicate clot formation (0.9 ± 13.8 vs. ?8.2 ± 15.1%, group 1 vs. 2, respectively, P = 0.01). Conclusion: Patients with chronic AF and thromboembolism have reduced LA and LV motion independently of LA size and LV ejection fraction. Tissue Doppler parameters may have potential to predict clot formation in these patients. (Echocardiography 2010;27:1038‐1048)     

Corneal topography and Schirmer testing in eyes with the Hudson-Stahli line

PURPOSE: To evaluate corneal topographic features and tear secretion in eyes with the Hudson-Stahli line. METHODS: Keratometry, computerized videokeratography and Schirmer testing were performed in 50 cases with bilateral Hudson-Stahli line, and 55 controls without the Hudson-Stahli line. Similar tests were performed in 21 subjects with unilateral Hudson-Stahli line. RESULTS: Corneal topographic features and keratometry in the horizontal meridian were similar in cases and controls, and in fellow eyes of subjects with unilateral Hudson-Stahli line. Keratometry in the vertical meridian in cases (43.01 +/- 2.01) was significantly lesser than in controls (43.94 +/- 1.77) (P = 0.01). This value was not different in fellow eyes of patients with unilateral Hudson-Stahli line. Schirmer testing revealed significantly greater tear secretion in cases (16.72 +/- 4.99 mm) compared to controls (12.57 +/- 3.62 mm) (P < 0.01). In subjects with unilateral Hudson-Stahli line, mean Schirmer values in the eye with the line (17.52 +/- 6.86 mm) were significantly greater than in eyes without (13.67 +/- 4.64 mm) (P = 0.04). CONCLUSION: Formation of the Hudson-Stahli line may be dependent on the presence of normal tear secretion in the eye.     

Bilateral macular hemorrhage caused by azathioprine-induced aplastic anemia in a corneal graft recipient

PURPOSE: To report the occurrence of bilateral macular hemorrhage following the use of azathioprine for immunosuppression in a corneal transplant recipient. METHODS: The patient underwent therapeutic penetrating keratoplasty for progressive fungal keratitis in his left eye. Although the infection did not recur, the graft failed with vascularization of the cornea in three quadrants. He underwent repeat penetrating keratoplasty 2 years later and was treated with azathioprine (100 mg daily) to enhance graft survival. Four months after instituting azathioprine therapy, he developed aplastic anemia and macular hemorrhage in both eyes. RESULTS: Fluorescein angiography revealed a preretinal location of the macular hemorrhage. After cessation of azathioprine therapy and treatment with blood component replacement, hematological parameters improved and the macular hemorrhage cleared with good visual recovery during the next 2 months. CONCLUSION: This report highlights the serious ocular and systemic complications that can occur following the use of systemic immunosuppressants after ophthalmic surgery.     

Routine blood counts in children with acute lymphoblastic leukaemia after completion of therapy: are they necessary?

Children who have completed treatment for acute lymphoblastic leukaemia (ALL) are commonly followed up for the first 5 years with regular full blood counts (FBCs) to monitor for relapse of disease. There is little evidence to suggest that this practice improves the detection rate of unexpected relapse. Surveillance FBCs, performed on 43 children with relapsed ALL between 1990 and 1999, were analysed. Of the 42 relapses in children off therapy, only two were detected by an abnormal FBC. Routine FBCs in asymptomatic children off therapy lacks specificity in detecting unexpected relapses and maybe safely discontinued.     

PABP2 polyalanine tract expansion causes intranuclear inclusions in oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy is caused by expansion of a (GCG)n trinucleotide repeat in the poly(A) binding protein 2 (PABP2) gene. The pathological hallmark of oculopharyngeal muscular dystrophy is the accumulation of intranuclear inclusions in muscle fibers. To test whether the polyalanine expansion of PABP2 directly leads to the formation of the nuclear aggregates, both normal and expanded PABP2 cDNAs were expressed in COS-7 cells. We find that expression of mutated PABP2 protein is sufficient for its accumulation as intranuclear inclusions.