Viral Capsid Is a Pathogen-Associated Molecular Pattern in Adenovirus Keratitis

Human adenovirus (HAdV) infection of the human eye, in particular serotypes 8, 19 and 37, induces the formation of corneal subepithelial leukocytic infiltrates. Using a unique mouse model of adenovirus keratitis, we studied the role of various virus-associated molecular patterns in subsequent innate immune responses of resident corneal cells to HAdV-37 infection. We found that neither viral DNA, viral gene expression, or viral replication was necessary for the development of keratitis. In contrast, empty viral capsid induced keratitis and a chemokine profile similar to intact virus. Transfected viral DNA did not induce leukocyte infiltration despite CCL2 expression similar to levels in virus infected corneas. Mice without toll-like receptor 9 (Tlr9) signaling developed clinical keratitis upon HAdV-37 infection similar to wild type mice, although the absolute numbers of activated monocytes in the cornea were less in Tlr9−/− mice. Virus induced leukocytic infiltrates and chemokine expression in mouse cornea could be blocked by treatment with a peptide containing arginine glycine aspartic acid (RGD). These results demonstrate that adenovirus infection of the cornea induces chemokine expression and subsequent infiltration by leukocytes principally through RGD contact between viral capsid and the host cell, possibly through direct interaction between the viral capsid penton base and host cell integrins

A randomised trial of oral versus intravenous opioids for treatment of pain after cardiac surgery

Background: Cardiac surgery and sternotomy are procedures accompanied by substantial postoperative pain which is challenging to treat. In general, intravenous (IV) opioids are used in the immediate postoperative phase, followed by oral opioids. Oral opioids are easier to use and generally less expensive. Our goal was thus to determine whether a new opioid preparation provides adequate analgesia after sternotomy. In particular, we tested the primary hypothesis that total opioid use (in morphine equivalents) is not greater with oral opioid compared with patient-controlled IV morphine. Our secondary hypothesis was that analgesic efficacy is similar with oral and IV opioids. Methods: A total of 51 patients having elective cardiac surgery were enrolled in this study. After rapid postoperative respiratory weaning, the patients were randomised into one of two groups receiving different types of analgesia: oral Targin (a combination of oxycodone–hydrochloride and the opioid antagonist naloxone hydrochloride-dihydrate) or patient-controlled IV morphine. Pain score (visual analogue scale), sedation (Ramsey score), respiratory rate and side effects were assessed at 3, 5, 7, 9 and 11 h after surgery, and every 6 h throughout the third postoperative evening. Results: The total opioid dose in morphine equivalent doses was significantly lower with oral opioid than with IV morphine (adjusted geometric means [95 % confidence interval]: 34 [29; 38] vs. 69 [61; 78] mg, respectively). Pain scores were similar in each group. Conclusions: Analgesic quality was comparable with oral and IV opioids, suggesting that postoperative pain even after very painful procedures can be sufficiently managed with oral opioids