"Toxic" facelifts.

The catalytic activity of the highly potent botulinum neurotoxins are confined to their N-terminal light chains ( approximately 50kDa). A full-length light chain for the type E neurotoxin with a C-terminal 6x His-tag, BoNT/E-LC, has been cloned in a pET-9c vector and over-expressed in BL21 (DE3) cells. BoNT/E-LC was purified to homogeneity by affinity chromatography on Ni-NTA agarose followed by exclusion chromatography using a Superdex-75 sizing column. The purified protein has very good solubility and can be stored stably at -20 degrees C; however, it seems to undergo auto-proteolysis when stored at temperature #10878;4-10 degrees C. BoNT/E-LC is active on its natural substrate, the synaptosomal associated 25kDa protein, SNAP-25, indicating that it retains a native-like conformation and therefore can be considered as a useful tool in studying the structure/function of the catalytic light chain. Recombinant BoNT/E-LC has been crystallized under five different conditions and at various pHs. Crystals diffract to better than 2.1A.

Botulinum Toxins↗

PubMed2004

Botulinum neurotoxin type B and physical therapy in the treatment of piriformis syndrome: a dose-finding study.

OBJECTIVE: To measure dosage effects of botulinum neurotoxin type B with physical therapy in piriformis syndrome. DESIGN: Prospective study of consecutive patients complaining of buttock pain and sciatica, measuring serial H-reflex tests in flexion, adduction, and internal rotation; visual analog scale; and adverse effects at 0, 2, 4, 8, and 12 wks. We used an electrophysiologic criterion for piriformis syndrome: a 1.86-msec prolongation of the H-reflex with the flexion, adduction, and internal rotation test. Four piriformis syndrome groups were identified. Serial groups were injected once with either 5000, 7500, 10,000, or 12,500 units of botulinum neurotoxin type B in successive months under electromyographic guidance in four separate locations of the affected piriformis muscle, with a 1-mo safety observation period between groups. Patients received physical therapy twice weekly for 3 mos. RESULTS: The flexion, adduction, and internal rotation test and visual analog scale declined significantly, correlating at 72% sensitivity and 77% specificity. A total of 24 of 27 study patients had >/=50% pain relief. Mean visual analog scale score declined from 6.7 to 2.3. A volume of 12,500 units of botulinum neurotoxin type B was superior to 10,000 units at 2 wks postinjection. The most severe adverse effects were dry mouth and dysphagia, approaching 50% of patients at 2 and 4 wks. CONCLUSION: Physical therapy and 12,500 units of botulinum neurotoxin type B seem to be safe and effective treatment for piriformis syndrome. In addition, the flexion, adduction, and internal rotation test seems to be an effective means of diagnosing piriformis syndrome and assessing its clinical improvement. Injection may benefit patients for >3 mos.

Botulinum Toxins↗