SummaryCynomolgus monkeys were anaesthetized with either intramuscular ketamine (10 mg/kg or intramuscular ketamine 2 mg/kg and medetomidine 50 Ilg/kg. Various physiological measurements were made once the animals were safe to handle and again 10 min later. Cardiovascular and respiratory function were well maintained with both regimens but the heart rate was lower and arterial-alveolar carbon dioxide gradient was higher in the animals that received medetomidine. In those animals that received medetomidine, atipamezole was given to reverse the medetomidine but there was no difference in recovery times between the two regimens. Anaesthesia was not entirely reliable with medetomidine/ketamine and we recommend caution when using this mixture.

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Background: Cynomolgus monkeys have a natural hypersensitivity to Ascaris suum antigen. Inhalation of antigen produces immediate and delayed allergic reactions and an influx of inflammatory cells into the lungs. This study investigated the production of nitric oxide (NO) and the chemokine eotaxin during this allergic response. The effect of bronchoscopy alone on lung inflammatory cells was also investigated along with the time course of the eosinophil influx into the lung. Methods: Allergic cynomolgus monkeys were challenged with antigen. Bronchoalveolar lavage (BAL) was performed before and after challenge, and end–tidal NO was measured before and 24 h after challenge. Eotaxin was measured in the BAL fluid 6, 24 and 72 h after challenge. One group of animals was treated with dexamethasone before challenge to block the influx of cells into the lung. Results: BLA alone induced an influx of neutrophils, but not eosinophils, into the lung 24 h later. A single antigen challenge produced a marked increase in BAL eosinophils that was apparent at 6 h but increased at 72 h after challenge. The increase at 6 h was largely blocked by dexamethasone. Three antigen challenges produced elevated BAL eosinophil levels that persisted for at least 8 weeks. Eotaxin levels rose dramatically 6 h after challenge and remained the same after 24 h. By 72 h, the eotaxin levels had returned to baseline. The increase in eotaxin at 6 h was nonsignificantly reduced by dexamethasone. Exhaled NO levels doubled 24 h after challenge and were not affected by dexamethasone. Conclusions: Eotaxin and NO production were increased after airway challenge in allergic monkeys. The rise in NO was not blocked by dexamethasone. The effects of bronchoscopy on the BAL can be avoided by using alternate lungs on consecutive occasions. Eosinophils persist in the BAL for many weeks after antigen challenge.

Runt pigs grow more slowly and never reach the same body weight as age-matched littermates. We hypothesized that IGF-I would be reduced in the runts and that postnatal nutrition would alter IGF-I concentration and tissue expression. Runt and control littermates were removed from 20 crossbred sows 20 to 28 h after birth. Tissues were collected from a baseline group (n = 4). The remaining pigs were fed porcine milk replacer at either 70 or 120 g/kg BW for 14 d (n = 8). Feed intake and body weight were measured daily, with plasma samples collected by jugular venipuncture throughout the experiment. Expression of IGF-I mRNA was measured in the liver and gastrocnemius with an RNase protection assay. At d 0, runts were significantly smaller than controls in all measurements, except brain weight. During the 14 d, the relative rate of growth was significantly faster and more efficient in runts than in controls; however, runts never attained the same absolute body weight as controls. Circulating IGF-I was significantly reduced at d 0 but was similar to that in controls by d 2 of feeding. The IGF-I mRNA expression in liver or gastrocnemius muscle was not different between control and runts at d 0 or 14 and was not affected by dietary intake. This study has shown that runt pigs grow in a compensatory manner for at least the first 2 wk of life. However, this growth response does not seem to be mediated by IGF-I.

Background The human repeated insult patch test (HRIPT) has a history of use in the fragrance industry as a component of safety evaluation, exclusively to confirm the absence of skin sensitization at a defined dose. Objective The aim of the study was to document the accumulated experience from more than 30 years of conducting HRIPTs. Methods A retrospective collation of HRIPT studies carried out to a consistent protocol was undertaken, with each study comprising a minimum of 100 volunteers. Conclusions The HRIPT outcomes from 154 studies on 134 substances using 16,512 volunteers were obtained. Most studies confirmed that at the selected induction/challenge dose, sensitization was not induced. In 0.12% of subjects (n = 20), there was induction of allergy. However, in the last 11 years, only 3 (0.03%) of 9854 subjects became sensitized, perhaps because of improved definition of a safe HRIPT dose from the local lymph node assay and other skin sensitization methodologies, as well as more rigorous application of the standard protocol after publication in 2008. This experience with HRIPTs demonstrates that de novo sensitization induction is rare and becoming rarer, but it plays an important role as an indicator that toxicological predictions from nonhuman test methods (in vivo and in vitro methods) can be imperfect.