Engineering Clustered Ligand Binding Into Nonviral Vectors: ��v��3 Targeting as an Example

The development of techniques to efficiently deliver genes using nonviral approaches can broaden the application of gene delivery in medical applications without the safety concerns associated with viral vectors. Here, we designed a clustered integrin-binding platform to enhance the efficiency and targetability of nonviral gene transfer to HeLa cells with low and high densities of α_vβ₃ integrin receptors. Arg-Gly-Asp (RGD) nanoclusters were formed using gold nanoparticles functionalized with RGD peptides and used to modify the surface of DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes with attached RGD nanoclusters resulted in either 5.4- or 35-fold increase in gene transfer efficiency over unmodified polyplexes for HeLa cells with low- or high-integrin surface density, respectively. The transfection efficiency obtained with the commercially available vector jetPEI-RGD was used for comparison as a vector without clustered binding. JetPEI-RGD exhibited a 1.2-fold enhancement compared to unmodified jetPEI in cells with high densities of α_vβ₃ integrin receptors. The data presented here emphasize the importance of the RGD conformational arrangement on the surface of the polyplex to achieve efficient targeting and gene transfer, and provide an approach to introduce clustering to a wide variety of nanoparticles for gene delivery.     

PREPARING THE MALE URETHRA FOR TRANSURETHRAL PROCEDURES

SUMMARY The antiseptic and analgesic effectiveness of different preparations of lignocaine gel used prior to flexible cystoscopy were studied in patients recruited over a 12-month period. This random study involved 106 patients in four groups. There appeared to be no difference in bacterial colonisation of the urethra between the groups. Urethral analgesia was improved when higher volumes of gel were used. It was concluded that high-volume gel preparations (>20 ml) with no antiseptic provided optimal conditions for flexible cystoscopy.     

Strategy for urinary protein analysis

SUMMARY: Recent studies have highlighted the intrinsic toxicity of filtered proteins and their contribution to deterioration of renal function. In-depth analysis of proteinuria may assess the degree of glomerular and/or tubular involvement and help in the prognostication of an individual patient. One should consider not only the quantity but also the quality of the urinary protein. Apart from quantitating the total urinary protein, assessment of the quality of the protein may be achieved by performing sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) for an overview assessment follow by automated nephelometry or simple radial immunodiffusion measurement of specific proteins for calculating the selectivity index and detecting tubular dysfunction.     

Peripheral pulmonary lesions: ultrasonography and ultrasonically guided aspiration biopsy

Twenty-five patients, each of whom had peripheral intrathoracic lesions that were smaller than 5.0 X 5.0 cm in size and not diagnosed by conventional methods, underwent real-time sonography and ultrasonically guided aspiration biopsy. The lesions included 18 nodules, two infiltrates, and five cavitary lesions. Sonography showed homogeneous hypoechoic or isoechoic density with well-defined margins in 16 of the nodules, and heterogeneous echogenicity with irregular margins in infiltrates. The cavitary lesions showed a hyperechoic ring with a central sonolucent area. Biopsy specimens were successfully obtained by percutaneous aspiration under ultrasound guidance in 24 (96%) of the patients, and a positive diagnosis was established in 21 (84%) by cytology and/or histology. All 17 malignant lesions were diagnosed by aspiration biopsy, while only four of seven benign lesions were diagnosed by this method. Two patients (8%) experienced minimal pneumothorax after aspiration biopsy. We conclude that real-time sonography, including ultrasonically guided aspiration biopsy, is a useful and safe method for examination of peripheral intrathoracic lesions and has a high diagnostic yield.     

Nail changes in chronic renal failure patients under haemodialysis

Background Chronic renal failure is known to cause various nail pathologies. They may be directly related to the renal condition itself or its complications or to the therapy. Objective To compare nail changes in end‐stage renal failure patients under haemodialysis with healthy persons and to study the potential relationship with various parameters in the patients. Patients and Methods The study comprised 100 patients with chronic renal failure under regular haemodialysis as well as 100 healthy control subjects of matched age and sex. Both groups were subjected to full history taking and thorough general and nail examination. Complete blood picture, liver and kidney function tests and fasting blood glucose level were investigated. Results Nail disorders were more prevalent in patients (76%) than in control group (30%). The half and half nail was the most common finding (20%) followed by – in descending manner – absent lunula, onycholysis, brittle nail, Beau's lines, clubbing, longitudinal ridging, onychomycosis, subungual hyperkeratosis, koilonychias, total leukonychia, splinter hemorrhage, pitting and pincer nail deformity. There was non‐significant correlation between nail changes and age of the patients or duration of haemodialysis. In addition, no evidence of significant relation was found between nail changes and both haemoglobin and albumin levels. Conclusion Frequent nail changes are observed on systematic nail examination of uraemic patients undergoing haemodialysis; however, the cause of them remains obscure and could not be traced to a particular abnormality in the renal condition, medication or the procedure itself and it needs further investigations.