Tetanus neurotoxin (TeNT) is among the most poisonous substances on Earth and a major cause of neonatal death in nonvaccinated areas. TeNT targets the neuromuscular junction (NMJ) with high affinity, yet the nature of the TeNT receptor complex remains unknown. Here, we show that the presence of nidogens (also known as entactins) at the NMJ is the main determinant for TeNT binding. Inhibition of the TeNT-nidogen interaction by using small nidogen-derived peptides or genetic ablation of nidogens prevented the binding of TeNT to neurons and protected mice from TeNT-induced spastic paralysis. Our findings demonstrate the direct involvement of an extracellular matrix protein as a receptor for TeNT at the NMJ, paving the way for the development of therapeutics for the prevention of tetanus by targeting this protein-protein interaction.

The purpose of this study was to determine the effect of a 48-month preventive dental program on the incidence of root caries in an urban, geriatric, noninstitutionalized population residing in an optimally fluoridated area. The 466 participants were randomly assigned to one of three groups at baseline. Group A (control): 171 subjects using a placebo mouthrinse daily; group B: 147 subjects receiving semiannual applications of a topical APF gel (1.2% F-) with the daily use of a placebo mouthrinse; group C: 148 subjects using a fluoridated mouthrinse daily, ACT (0.05% F-). At baseline, the numbers of surfaces at risk, and decayed and filled surfaces were recorded. After 48 months, in addition, the number of reversed and new lesions were determined, and the incremental DMFS calculated. The data were analyzed by ANCOVA. The incremental DMFS were: A = 0.91, B = 0.27, C = 0.26. The incremental DMFS in groups B and C were significantly lower than in group A (P < .05). The number of reversed lesions in group C (1.53 +/- 2.03) was significantly greater than in group A (1.11 +/- 1.74) and group B (1.01 +/- 1.86) (P < .05). The number of new lesions in group B (1.36 +/- 2.00) was significantly less than in group A (1.99 +/- 2.65) (P < .05). The daily use of the fluoride mouthrinse significantly increased the number of reversed lesions.

This study determined whether an acute alcohol dose could inhibit the refeeding response in starved muscle. Rats starved for 24 h were pretreated with alcohol or saline before refeeding by intragastric or intravenous infusion of enteral diet (ENT), total parenteral nutrition (TPN), or saline. Refeeding by TPN or ENT stimulated increases in the fractional rate of protein synthesis ( k s) in skeletal muscle. Alcohol prevented the increase in k s when refeeding occurred intragastrically (TPN or ENT) ( P < 0.001) but not intravenously (TPN). Upon intragastric refeeding, alcohol inhibited the increase in both eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and p70 S6 kinase (p70S6K) phosphorylation in plantaris but caused only partial inhibition in soleus muscle (ENT only). When rats were refed intravenously, alcohol had no effect on the increased 4E-BP1 or p70S6Kphosphorylation in either muscle. Plasma insulin levels were augmented by alcohol. Alcohol-related changes in plasma amino acid concentrations were similar irrespective of the route of feeding, whereas IGF-I levels showed differential changes. This is the first study to demonstrate that acute alcohol ingestion impedes the starved-to-fed response in skeletal muscle.

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