RESUMO
The use of pyrogen tests to assess the risk of endotoxin in biological products has increased recently due to concerns of some regulatory authorities about products exhibiting low endotoxin recovery (LER). Manufacturers increasingly seek to reduce the use of animals unless essential to assure patient safety. The current study compares the ability of the monocyte activation test (MAT) and the bacterial endotoxin test (BET) to the rabbit pyrogen test (RPT) to detect endotoxin spikes in samples of products shown to exhibit LER. Product samples or water were spiked with endotoxin and held for three days or tested immediately in the BET, the RPT, and two variations of the MAT at the same time. Results show high sensitivity to endotoxin of both the BET and MAT, and much lower sensitivity of the RPT, indicating that much higher levels of reference standard endotoxin are required to induce pyrogenicity in the RPT than the 5 endotoxin units (EU) per kg common threshold. The results of the BET and MAT correlated well for the detection of endotoxin spike in water. We also show that LER (masking of endotoxin) found in the BET is also seen in the MAT and RPT, suggesting that the products themselves elicit a biological inactivation of spiked endotoxin over time, thereby rendering it less or non-pyrogenic. We conclude that the non-animal MAT option is a suitable replacement for the RPT to measure spiked endotoxin in biopharmaceuticals.
Assuntos
Endotoxinas , Pirogênios , Animais , Coelhos , Endotoxinas/toxicidade , Pirogênios/toxicidade , Alternativas aos Testes com Animais , Monócitos , Bioensaio/métodosRESUMO
BACKGROUND: Walking is a key focus of public health interventions yet is particularly uncommon in rural residents. This study's purpose was to determine whether a multilevel community intervention affected rates of moderate physical activity, in particular walking. METHODS: A quasi-experimental design examined changes in walking in six rural intervention communities in Missouri and six comparison communities in Arkansas and Tennessee in 2003-2004. Interventions were developed with community input and included individually tailored newsletters; interpersonal activities that stressed social support and health provider counseling; and community-wide events such as fun walks. A dose variable estimated exposure to intervention activities. Primary outcomes were rates of walking and moderate physical activity in the past week. RESULTS: At follow-up (n = 1531), the percentage of respondents who met the recommendation for walking was the same across the intervention and comparison areas. Among the dependent variables, walking showed some evidence of a positive linear trend across dose categories (P = 0.090). After adjusting for covariates and baseline rates, intervention participants in the moderate and high dose categories were about three times more likely to meet recommended guidelines for walking. CONCLUSIONS: Some evidence of effectiveness was shown for a multilevel intervention approach to promote walking.