A neonatal piglet model reveals interactions between nasal microbiota and influenza A virus pathogenesis.

While vaccination and therapeutics for prevention/treatment of influenza are available, new strategies are needed to combat influenza disease in susceptible populations, particularly young children and newborns. Host associated microbiota play an important role in modulating the virulence of numerous pathogens, including the influenza A virus. In this study, we examined microbiome-influenza interactions in a neonatal piglet model system. The nasal microbiome of newborn piglets was longitudinally sampled before and after intranasal infection with recombinant viruses expressing hemagglutinins (HAs) derived from distinct zoonotic H1 subtypes. We found that viruses expressing different parental HAs manifested unique patterns of pathogenicity, and varied impacts on microbial community diversity. Despite these virus specific differences, a consistent microbial signature of viral infection was detected. Our results indicate that influenza A virus infection associates with the restructuring of nasal microbiome and such shifts in microbial diversity may contribute to outcomes of viral infection in neonatal piglets.

Comparison of a Minimally Invasive Transthoracic Approach and a Surgical Method for Intrapleural Injection of Tumor Cells in Mice.

Intrapleural injections can be used in mice to deliver therapeutic and diagnostic agents and to model human disease processes (for example, pleural fluid accumulation, malignant pleural disease, and lung cancers). In the context of establishing cancer models, minimally invasive methods of intrapleural injection are desirable because inflammation at the injection site can have a major impact on tumor growth and progression. Common approaches for intrapleural injection include surgical exposure of the thoracic wall or the diaphragm prior to injection; however, these invasive procedures require tissue dissection that triggers an undesirable inflammatory response and increases the risk of pneumothorax. While nonsurgical procedures can minimize this concern, 'blind' injections may lead to off target inoculation. In this study, we hypothesized that a minimally invasive transthoracic approach (MI-TT) would produce a tumor distribution and burden similar to that of a surgical transabdominal approach (SX-TA). Prior to performing the procedures on live mice, surgeons were trained using cadavers and terminal procedures. Then a total of 14 nude mice (female, 4 to 6 wk old) were injected with 50 µL (5 million) A549-Luc2 human cancer cells either using the MI-TT (n = 8) or SX-TA (n = 6) approach under carprofen analgesia and isoflurane anesthesia. Our results indicate that with training, a minimally invasive transthoracic approach for intrapleural injection provides more consistent tumor placement and a greater tumor burden than does the surgical method. However, additional studies are necessary to confirm anatomic placement and characterize tumor profiles.

Comparison of Low- and High-temperature Cagewash Cycles for Sanitation of Rodent Housing Equipment in Research Facilities.

Sanitation guidelines for animal research facilities state that disinfection is achieved by application of high-temperature water (143 to 180 °F [62 to 82 °C]) or detergents and disinfectants. However, these guidelines are based on requirements for pasteurization, which may be unnecessarily stringent for the sanitation of nonfood items and do not address the theoretical sanitation potential of water at temperatures below 143 °F (62 °C). Recent literature indicates that water temperatures below 143 °F (62 °C) can also provide effective sanitation. In this study, we compared cagewash cycles at low (100 °F [38 °C] and 120 °F [49 °C]) and high (standard) (180 °F [82 °C]) temperatures and evaluated sanitation efficacy by using ATP swabs and RODAC plates. Low-temperature loads were washed either with or without prior treatment of a chemical disinfectant (10% bleach). The 100 °F (38 °C) cycle was not sufficient for sanitization without bleach pretreatment. However, the 120 °F (49 °C) cycle effectively sanitized cages without bleach pretreatment. Validation of effective sanitation at a lower water temperature (120 °F [49 °C]) can improve cagewash logistics and reduce costs as compared with standard (180 °F [82 °C]) high-temperature cycles.

Sustained-Release Buprenorphine Improves Postsurgical Clinical Condition but Does Not Alter Survival or Cytokine Levels in a Murine Model of Polymicrobial Sepsis.

Cecal ligation and perforation (CLP) is a common technique for studying sepsis in mice. Because of the invasiveness of the procedure and its effects on clinical condition, many animal care and use committees require the use of analgesics with CLP. However, some analgesics have immunomodulatory effects and thus can hinder the overall research outcomes of a project. Here we sought to determine the effects of buprenorphine hydrochloride (Bup HCl) compared with sustained-release buprenorphine (Bup SR) on clinical condition, plasma concentrations of monocyte chemoattractant protein (MCP) 1 and IL6, and overall mortality in a murine CLP model of sepsis. Male C57/BL6 mice underwent CLP surgery and received Bup HCl or Bup SR as a component of an IACUCapproved analgesic dosing regimen. Mice were observed twice daily for clinical condition scoring by the same blinded investigator for the duration of the study. MCP1 and IL6 levels and mortality did not differ significantly between the 2 groups. Scoring of clinical condition revealed a significant decrease in behaviors associated with perceived pain at 12 and 24 h postoperatively in mice in the Bup SR group compared with the Bup HCl group. Because of the lack of significant effect on MCP1 and IL6 levels and mortality and the superior analgesic effects of Bup SR, we recommend the use of Bup SR for analgesia during the murine CLP model of sepsis.