Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab

Pharmacological inhibition of VEGF-A has proven to be effective in inhibiting angiogenesis and vascular leak associated with cancers and various eye diseases. However, little information is currently available on the binding kinetics and relative biological activity of various VEGF inhibitors. Therefore, we have evaluated the binding kinetics of two anti-VEGF antibodies, ranibizumab and bevacizumab, and VEGF Trap (also known as aflibercept), a novel type of soluble decoy receptor, with substantially higher affinity than conventional soluble VEGF receptors. VEGF Trap bound to all isoforms of human VEGF-A tested with subpicomolar affinity. Ranibizumab and bevacizumab also bound human VEGF-A, but with markedly lower affinity. The association rate for VEGF Trap binding to VEGF-A was orders of magnitude faster than that measured for bevacizumab and ranibizumab. Similarly, in cell-based bioassays, VEGF Trap inhibited the activation of VEGFR1 and VEGFR2, as well as VEGF-A induced calcium mobilization and migration in human endothelial cells more potently than ranibizumab or bevacizumab. Only VEGF Trap bound human PlGF and VEGF-B, and inhibited VEGFR1 activation and HUVEC migration induced by PlGF. These data differentiate VEGF Trap from ranibizumab and bevacizumab in terms of its markedly higher affinity for VEGF-A, as well as its ability to bind VEGF-B and PlGF.     

Thalidomide for Treatment of Bleeding Angiodysplasias during Hemodialysis

Renal transplant patients are more prone to tuberculosis infection due to the underlying intense immunosuppression, with an incidence 20–74 times higher than that in the general population. It is associated with graft dysfunction and increased mortality rates. It can be frequently pulmonary but extra-pulmonary involvement is not rare, and in the latter case, it may be misinterpreted as genital malignancies. In this case report, we discuss a renal transplant patient with pelvic pain and fever, who was later diagnosed as having abdominopelvic tuberculosis.     

Effects of Strength vs. Ballistic-Power Training on Throwing Performance

The purpose of the present study was to investigate the effects of 6 weeks strength vs. ballistic-power (Power) training on shot put throwing performance in novice throwers. Seventeen novice male shot-put throwers were divided into Strength (N = 9) and Power (n = 8) groups. The following measurements were performed before and after the training period: shot put throws, jumping performance (CMJ), Wingate anaerobic performance, 1RM strength, ballistic throws and evaluation of architectural and morphological characteristics of vastus lateralis. Throwing performance increased significantly but similarly after Strength and Power training (7.0-13.5% vs. 6.0-11.5%, respectively). Muscular strength in leg press increased more after Strength than after Power training (43% vs. 21%, respectively), while Power training induced an 8.5% increase in CMJ performance and 9.0 - 25.8% in ballistic throws. Peak power during the Wingate test increased similarly after Strength and Power training. Muscle thickness increased only after Strength training (10%, p < 0.05). Muscle fibre Cross Sectional Area (fCSA) increased in all fibre types after Strength training by 19-26% (p < 0.05), while only type IIx fibres hypertrophied significantly after Power training. Type IIx fibres (%) decreased after Strength but not after Power training. These results suggest that shot put throwing performance can be increased similarly after six weeks of either strength or ballistic power training in novice throwers, but with dissimilar muscular adaptations.

Key points

• Ballistic-power training with 30% of 1RM is equally effective in increasing shot put performance as strength training, in novice throwers, during a short training cycle of six weeks.
• In novice shot putters with relatively low initial muscle strength/mass, short-term strength training might be more important since it can increase both muscle strength and shot put performance.
• The ballistic type of power training resulted in a significant increase of the mass of type IIx muscle fibres and no change in their proportion. Thus, this type of training might be used effectively during the last weeks before competition, when the strength training load is usually reduced, in order to increase muscle power and shot put performance in novice shot putters.

Key words: Shot put, muscle fibres, ultrasound, ballistic training, muscle mass.     

Orbitopalpebral repair after 835 excisions of malignant tumours

Repair of any defect in the eyelid depends on its size and position and the state of the surrounding tissues. Basal cell carcinoma (BCC) is the most common malignant tumour of the eyelids, and squamous cell carcinoma (SCC), mixed carcinomas or basosquamous cell carcinomas (BSC), and cutaneous melanomas (CM), also invade the eyelids and periocular zones. Reconstruction of the eyelids and associated orbital structures after resection requires a complete understanding of the anatomy. The adequacy of the reconstruction is judged by the quality of functional restoration and the aesthetic appearance. The purpose of this study was to document various, simple or complex reconstructive procedures that may be used after excision of malignant tumours of the eyelids and to assess the outcome of surgical treatment.     

Understanding macrographia in children with autism spectrum disorders

It has been consistently reported that children with autism spectrum disorders (ASD) show considerable handwriting difficulties, specifically relating to accurate and consistent letter formation, and maintaining appropriate letter size. The aim of this study was to investigate the underlying factors that contribute to these difficulties, specifically relating to motor control. We examined the integrity of fundamental handwriting movements and contributions of neuromotor noise in 26 children with ASD aged 8–13 years (IQ > 75), and 17 typically developing controls. Children wrote a series of four cursive letter l's using a graphics tablet and stylus. Children with ASD had significantly larger stroke height and width, more variable movement trajectory, and higher movement velocities. The absolute level of neuromotor noise in the velocity profiles, as measured by power spectral density analysis, was significantly higher in children with ASD; relatively higher neuromotor noise was found in bands >3 Hz. Our findings suggest that significant instability of fundamental handwriting movements, in combination with atypical biomechanical strategies, contribute to larger and less consistent handwriting in children with ASD.