Nocturnal haemoglobin oxygen desaturation in urban and rural East African paediatric cohorts with and without sickle cell anaemia: a cross-sectional study.

Low haemoglobin oxygen saturation (SpO2) predicts complications in children with sickle cell anaemia (SCA) in the North but there are few data from Africa, where the majority of the patients reside. We measured daytime and overnight SpO2 in children with SCA in routine follow-up clinic, and controls without symptoms of SCA, comparing rural (Kilifi, Kenya) and urban (Dar-es-Salaam, Tanzania) cohorts. Daytime SpO2 was lower in 65 Tanzanian children with SCA (TS; median 97 (IQR 94-100)%); p<0.

Development of improved SNAP25 endopeptidase immuno-assays for botulinum type A and E toxins.

Botulinum neurotoxins contain proteases that cleave specific intra-neural proteins essential for neurotransmitter release. Toxin types A, E and C1 intra-cellularly cleave SNAP25 resulting in a flaccid paralysis. As a consequence, various different endopeptidase assays have been developed to specifically detect the toxins enzymatic activity, however, many of these suffer from variability, low sensitivity or unwanted interference exerted by product specific excipients.

Application of an in vitro endopeptidase assay for detection of residual toxin activity in tetanus toxoids.

Tetanus vaccine is composed of chemically denatured tetanus toxin (TeNT), thus safety testing requires confirmation of freedom from residual and reversible toxicity. Currently, TeNT activity is estimated using in vivo assay models. Information that TeNT acts by selectively inactivating protein leading to the blocking of release of neurotransmitters has provided the opportunity to develop in vitro biochemical assay for toxin activity.

Recombinant SNAP-25 is an effective substrate for Clostridium botulinum type A toxin endopeptidase activity in vitro.

Bacterial neurotoxins are now being used routinely for the treatment of neuromuscular conditions. Alternative assays to replace or to complement in vivo bioassay methods for assessment of the safety and potency of these botulinum neurotoxin-based therapeutic products are urgently needed. Advances made in understanding the mode of action of clostridial neurotoxins have provided the basis for the development of alternative mechanism-based assay methods.

Therapeutic botulinum type A toxin: factors affecting potency.

The type A neurotoxin produced by Clostridium botulinum is a potent neuromuscular blocking agent which causes paralysis by preventing the release of neurotransmitter from motor neurons. This property has resulted in the use of the toxin in the treatment of a number of neuromuscular diseases involving muscle spasms. At present, the only recognised assay to estimate accurately the potency of botulinum toxin in clinical preparations is bioassay, in which lethality is used as the endpoint.