A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection.

Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM. Small-molecule inhibition of Bax/Bak oligomerization allowed cells to evade apoptotic stimuli and rescued neurons from death after excitotoxicity, demonstrating that oligomerization of Bax is essential for MOMP. Our discovery of small-molecule Bax/Bak inhibitors provides novel tools for the investigation of the mechanisms leading to MOMP and will ultimately facilitate development of compounds inhibiting Bax/Bak in acute and chronic degenerative diseases.

Percutaneous plating of lower limb long bone fractures.

We conducted a study on indirect reduction and percutaneous plating in the treatment of 22 cases (mean age 50.3, S.D. 18.5, range 18-88) of non-diaphyseal fractures of long bones of the lower limb mainly using the lateral tibial head buttress plate. All cases achieved radiological union and full weight bearing walking. No major malalignment resulted and only one Gustilo III-b compound fracture required bone grafting. None required revision surgery from problem with union. One case required revision in the early learning phase and another patient suffered wound complication from self-herbal application which required local flap surgery. The satisfactory functional results and the lack of soft tissue complications suggest that this method should be considered in metaphyseal fractures where intramedullary nails are not applicable.

Gross motor function measure for children with cerebral palsy.

The aim of this study was to compare the pattern of motor dysfunction in Hong Kong Chinese children with spastic diplegic and the athetoid type of cerebral palsy (CP) by the Gross Motor Function Measure (GMFM). The GMFM was first tested on its content validity in differentiating the items suitable for testing on upper and lower limb function, followed by test-retest and inter-rater reliability studies, before it was used in a within-subject experiment comparing upper and lower gross motor function in two types of CP, respectively. Children with spastic diplegia (n=18) and with athetosis (n=19) were recruited from three pre-school centres, schools for physically handicapped children and centres of the Hong Kong Spastic Association in Hong Kong. The GMFM, a standardized outcome measure of the motor function in children with CP, was used in comparing mean scores of motor tasks involving upper limbs and those not involving upper limbs in the athetoid and spastic cerebral palsied children. The scores were significantly higher for the children in the spastic diplegic group, but there was no significant difference in the performance of static and dynamic motor tasks of the GMFM between the children in the two groups.