Targeted drug delivery systems have distinct advantages over conventional dosage forms. In the present ap-proach, flexible liposomal drug carriers (transferosomes) were formulated and their physicochemical properties were studied compared with conventional liposomal and niosomal formulae. Lipid vesicles composed of lecithin, cholesterol, span 60, and sodium deoxycholate (SDC) were prepared by thin film hydration method. Photodynamic treatment of subcutaneous Ehrlich tumor using prepared and pharmaceutically studied hydrogel containing 1% hydrophilic toluidine blue (TB) loaded transferosomes was evaluated. The results showed that transferosomes containing both span 60 and SDC were of the highest entrapment efficiency (> 82%), particle size (1.36 ?m) and released 52% of its content within 2 hours. The in vivo study on BALB/C mice showed that there was a marked increase in the survival time and decrease in the tumor size in mice group treated with transferosomal (span 60 and SDC) hydrogel for 1h followed by irradiation with 90J/cm2 from 650 nm diode laser twice weekly compared with animals treated with free TB and irradiated only. Furthermore, there was a marked deep necrosis of tumor cells, which may be attributed to the deep penetration of TB through skin layers. These findings suggest the use of TB loaded transferosomes in topical targeted photodynamic treatment of skin tumors.

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Achieving dry weight after hemodialysis (HD) is critical as chronic fluid over-load can result in left ventricular hypertrophy, while small fluid shifts may result in intra-dialytic morbid events (IME). In the pediatric population, estimating dry weight can be difficult due to growth while on dialysis. Continuous non-invasive monitoring of the hematocrit (NIVM) has been proposed as a more accurate method of estimating dry weight. Fifteen pediatric patients on chronic HD (6 males and 9 females; mean age 11.4 ± 2.28 years) were included in an uncontrolled prospective study involving three phases. In phase 1, patients were observed for one month for their dry weight and frequency of IME. Phase 2 consisted of using NIVM-guided ultrafiltration algorithm for rate of blood volume (BV) reduction and post-dialysis refill, recommending an intra-dialytic reduction in BV of 8% in the first hour and <4% per hour thereafter and without significant post-dialytic vascular refill. Phase 3 comprised a one month period for comparing the results. IME decreased from 33 episodes per 180 sessions in phase 1 to 4 per 180 sessions during phase 3 (P = 0.04), without a significant difference in pre-systolic or post-systolic or mean BP before and after the intervention (all P >0.1). In phase 1, 40% of patients experienced no IME, 33% experienced one or two IME while 27% experienced more than two IME; during phase 3, 80% experienced no IME, 20% experienced one or two IME while no one experienced more than two IME. NIVM can serve as an objective method for determining dry weight as well as predicting and preventing IME in the pediatric population on maintenance HD.

Primary hyperoxaluria type 1 (PH1) is a rare disease that is challenged by the overproduced oxalate and commonly presented with radiopaque renal stones or obstructive uropathy. This study aimed to report clinical presentations, renal replacement therapy (RRT), and outcome of PH1 in end stage kidney disease (ESKD) children. This is an observational cohort study. Data of 22 patients with ESKD due to PH1 were analyzed at Pediatric Nephrology Unit, Faculty of Medicine Cairo University. Infantile onset patients (n = 10) had worst renal outcome (80% with ESRD at presentation, p = 0.019) and worse patient outcome (mortality 40%, p = 0.016) than juvenile (n = 9) and late onset (PH1 n = 3) patients. RRT modalities include peritoneal dialysis (PD) in 7 (31.8%), hemodialysis (HD) in 11 (50%), and combined liver kidney transplantation (CLKT) in 4 (18.2%) patients. Infectious complications were encountered in 42.8% of PD patients. Better HD adequacy was observed with frequent HD (n = 6) and/or HD via arteriovenous fistula (AVF) than with infrequent dialysis (n = 5) and/or via central venous line (CVL) (p = 0.0001 and 0.0047, respectively). Morbidity and mortality (infection related) rates of the whole cohort were 63.6% and 31.8%, respectively. Clinical presentation of PH1 varies according to the age of onset (infantile onset being the most aggressive form). Aggressive HD (better through AVF) is needed to achieve acceptable HD adequacy, PD was challenged by infection. Infection found to be the main cause of mortality even after successful CLKT.

Vascular access represents a lifeline for children undergoing hemodialysis. A failure of vascular access among patients receiving regular hemodialysis is associated with increased morbidity, mortality and costs. We assessed the possibility of using soluble adhesion molecules as reliable predictors of vascular access failure in children on hemodialysis. Moreover, we evaluated whether there is an association among the different studied adhesion molecules in hemodialysis patients with thrombosed and non-thrombosed arteriovenous fistula fistulas (AVFs). This study included 55 hemodialysis children, 36 with good access and 19 with access failure, and 20 healthy volunteers. Forty-four patients had native AVFs and 11 patients had tunneled permanent catheter (11with thrombosed and 33 with non-thrombosed AVFs). Serum-soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) were measured using ELISA technique. A significant increase was found in the levels of sVCAM-1, sICAM-1, sE-selectin and sP-selectin versus controls and all hemodialysis patients, hemodialysis patients with good access and hemodialysis patients with access failure (P=0.001 for sVCAM-1 and sICAM-1 and P=0.0001 for sE-selectin and sP-selectin). A significant increase was found in the levels of sVCAM-1, sE-selectin and sP-selectin in both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs versus controls (P=0.0001 for all parameters). There was significant difference between both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs as regard to sVCAM-1 (54.64±30.82 versus 25.69±27.96ng/ml, P=0.04). Both sICAM-1 and sP-selectin were positively correlated with the erythropoietin (EPO) dose in hemodialysis children (r=0.31, P=0.04 and r=0.32, P=0.04, respectively). A significant positive association was found between E-selectin and sP-selectin in hemodialysis patients with thrombosed AVFs (r=0.83, P=0.04). There was a significant correlation between sVCAM-1 and EPO dose in thrombosed AVF group (r=0.84, P=0.01). The assessment of serum sVCAM-1 might be useful for the identification of the chronic hemodialysis patients at an increased risk for native AVFs thrombosis. The role of EPO in vascular access failure should be taken into consideration. The clinical relevance of these observations warrants further investigations.

BACKGROUND: Renal transplantation (RTx) is the treatment of choice for paediatric end-stage renal disease (ESRD). A major cause of morbidity and mortality after RTx is cardiovascular disease. Independent predictors of cardiovascular events were shown to constitute an endothelial dysfunction (ED). This study aims to evaluate Visfatin serum level in comparison to brachial artery flow-mediated dilatation (FMD) as a marker of endothelial dysfunction in paediatric RTx recipients.

METHODS: Visfatin serum level has been evaluated in 30 patients on regular hemodialysis (HD), 36 patients post-RTx and 30 controls as a measure for ED, and has been compared to brachial artery FMD.

RESULTS: Visfatin level in transplant recipients was significantly lower than the hemodialysis group as well as FMD was better in transplant recipients. In spite of marked improvement of FMD and marked reduction of visfatin in post-RTx no direct statistical correlation was found between serum Visfatin level and flow-mediated dilatation.

CONCLUSION: Pediatric RTx recipients show lower serum Visfatin level and better FMD than those on regular hemodialysis, reflecting less endothelial dysfunction (ED) and less cardiovascular risk. FMD in kidney transplant recipients tends to be less than normal subjects while visfatin level of the same group is similar to controls. Pediatric RTx appears to have a positive impact on the growth development of children with ESRD.

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