Vitamin E is ineffective for symptomatic relief of knee osteoarthritis: a six month double blind, randomised, placebo controlled study.

OBJECTIVE: There is a putative role for antioxidant treatment in osteoarthritis (OA) based on animal, epidemiological, and human clinical studies. Vitamin E, a fat soluble vitamin, is one of the major dietary antioxidants. Short term clinical studies using vitamin E in the form of alpha-tocopherol suggested a benefit over placebo of similar dimension to that of diclofenac for relief of OA pain. METHODS: A six month, double blind, randomised, placebo controlled study of vitamin E 500 IU/day was carried out. Primary outcome measures were pain, stiffness, and function. Statistical analysis was performed on an intention to treat basis. RESULTS: 77 patients were included in the study. Vitamin E showed no benefit over placebo at one month, three months, or six months for any of the outcome measures. The placebo group had higher pain levels (p=0.15) and body mass index (p=0.03) at baseline, and lower pain levels (p=0.02) at completion of the study. Radiological score, exercise score, age, or antioxidant intake at baseline or six months did not differ between the groups. The reasons for the better performance of the placebo group are uncertain but may relate to the initially higher pain score and subsequent regression to the mean. CONCLUSIONS: Vitamin E shows no benefit for the management of symptomatic knee OA. The role of vitamin E in preventing OA progression is currently under investigation.

Detection of functional PTEN lipid phosphatase protein and enzyme activity in squamous cell carcinomas of the head and neck, despite loss of heterozygosity at this locus.

The human tumour suppressor gene PTEN located at 10q23 is mutated in a variety of tumour types particularly metastatic cases and in the germline of some individuals with Cowdens cancer predisposition syndrome. We have assessed the status of PTEN and associated pathways in cell lines derived from 19 squamous cell carcinomas of the head and neck. Loss of heterozygosity is evident at, or close to the PTEN gene in 5 cases, however there were no mutations in the remaining alleles. Furthermore by Western analysis PTEN protein levels are normal in all of these SCC-HN tumours and cell lines. To assess the possibility that PTEN may be inactivated by another mechanism, we characterized lipid phosphatase levels and from a specific PIP3 biochemical assay it is clear that PTEN is functionally active in all 19 human SCCs. Our data strongly suggest the possibility that a tumour suppressor gene associated with development of SCC-HN, other than PTEN, is located in this chromosomal region. This gene does not appear to be MXI-1, which has been implicated in some other human tumour types. PTEN is an important negative regulator of PI3Kinase, of which subunit alpha is frequently amplified in SCC-HN. To examine the possibility that PI3K is upregulated by amplification in this tumour set we assessed the phosphorylation status of Akt, a downstream target of PI3K. In all cases there is no detectable increase in Akt phosphorylation. Therefore there is no detectable defect in the PI3K pathway in SCC-HN suggesting that the reason for 3q26.3 over-representation may be due to genes other than PI3K110alpha.