Role of acid-sensing ion channel 3 in sub-acute-phase inflammation

<p>Abstract</p> <p>Background</p> <p>Inflammation-mediated hyperalgesia involves tissue acidosis and sensitization of nociceptors. Many studies have reported increased expression of acid-sensing ion channel 3 (ASIC3) in inflammation and enhanced ASIC3 channel activity with pro-inflammatory mediators. However, the role of ASIC3 in inflammation remains inconclusive because of conflicting results generated from studies of <it>ASIC3 </it>knockout (<it>ASIC3</it>^-/-) or dominant-negative mutant mice, which have shown normal, decreased or increased hyperalgesia during inflammation.</p> <p>Results</p> <p>Here, we tested whether ASIC3 plays an important role in inflammation of subcutaneous tissue of paw and muscle in <it>ASIC3</it>^-/-mice induced by complete Freund's adjuvant (CFA) or carrageenan by investigating behavioral and pathological responses, as well as the expression profile of ion channels. Compared with the <it>ASIC3</it>^+/+controls, <it>ASIC3</it>^-/-mice showed normal thermal and mechanical hyperalgesia with acute (4-h) intraplantar CFA- or carrageenan-induced inflammation, but the hyperalgesic effects in the sub-acute phase (1–2 days) were milder in all paradigms except for thermal hyperalgesia with CFA-induced inflammation. Interestingly, carrageenan-induced primary hyperalgesia was accompanied by an <it>ASIC3</it>-dependent <it>Nav1.9 </it>up-regulation and increase of tetrodotoxin (TTX)-resistant sodium currents. CFA-inflamed muscle did not evoke hyperalgesia in <it>ASIC3</it>^-/-or <it>ASIC3</it>^+/+mice, whereas carrageenan-induced inflammation in muscle abolished mechanical hyperalgesia in <it>ASIC3</it>^-/-mice, as previously described. However, <it>ASIC3</it>^-/-mice showed attenuated pathological features such as less CFA-induced granulomas and milder carrageenan-evoked vasculitis as compared with <it>ASIC3</it>^+/+mice.</p> <p>Conclusion</p> <p>We provide a novel finding that ASIC3 participates in the maintenance of sub-acute-phase primary hyperalgesia in subcutaneous inflammation and mediates the process of granuloma formation and vasculitis in intramuscular inflammation.</p

Comparative morphological trade-offs between pre- and post-copulatory sexual selection in Giant hissing cockroaches (Tribe: Gromphadorhini)

Sperm competition theory predicts that animals face a trade-off between investment in weaponry and investment in ejaculate composition. Within the Madagascan giant hissing cockroaches (Tribe Gromphadorhini) differences in morphology exist that may indicate differing strategies of male-male competition. We compared relative pronotal horn length using high-resolution X-ray CT scanning data, relative testes mass, and male-male agonistic behaviour between two species of hissing cockroaches, Gromphadorhina oblongonota and Aeluropoda insignis. The gross morphology and behaviour of these two species indicated that G. oblongonota is selected for pre-copulatory mate acquisition and that A. insignis is selected for post-copulatory sperm competition. We found evidence for a trade-off when investing in testes mass vs. horn length between the species. The large, aggressive G. oblongonota follows a strategy of greater investment in weapons at the expense of testes mass while the smaller, less-aggressive A. insignis invests in relatively greater testes mass and less in pronotal weapon length. We also found evidence of a trade-off within each species, where individuals invest more heavily in weapon length at the expense of testes mass. These findings support the predictions of pre- and postcopulatory competitive investment trade-offs for a relatively understudied Tribe of cockroaches

An “Electronic Fluorescent Pictograph” Browser for Exploring and Analyzing Large-Scale Biological Data Sets

Background. The exploration of microarray data and data from other high-throughput projects for hypothesis generation has become a vital aspect of post-genomic research. For the non-bioinformatics specialist, however, many of the currently available tools provide overwhelming amounts of data that are presented in a non-intuitive way. Methodology/Principal Findings. In order to facilitate the interpretation and analysis of microarray data and data from other large-scale data sets, we have developed a tool, which we have dubbed the electronic Fluorescent Pictograph – or eFP – Browser, available a

Antinociceptive and Anti-Inflammatory Activities of the Ethanol Extract of Annona muricata L. Leaves in Animal Models

Antinociceptive and anti-inflammatory activities of the ethanol extract from Annona muricata L. leaves were investigated in animal models. The extract delivered per oral route (p.o.) reduced the number of abdominal contortions by 14.42% (at a dose of 200 mg/kg) and 41.41% (400 mg/kg). Doses of 200 and 400 mg/kg (p.o) inhibited both phases of the time paw licking: first phase (23.67% and 45.02%) and the second phase (30.09% and 50.02%), respectively. The extract (p.o.) increased the reaction time on a hot plate at doses of 200 (30.77% and 37.04%) and 400 mg/kg (82.61% and 96.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by the ethanol extract (p.o.) at doses of 200 (23.16% and 29.33%) and 400 mg/kg (29.50% and 37.33%) after 3 to 4 h of application of carrageenan, respectively. Doses of 200 and 400 mg/kg (p.o.), administered 4 h before the carrageenan injection, reduced the exudate volume (29.25 and 45.74%) and leukocyte migration (18.19 and 27.95%) significantly. These results suggest that A. muricata can be an active source of substances with antinociceptive and anti-inflammatory activities

Pharmacological Proprieties of the Ethanol Extract of Muehlenbeckia platyclada (F. Muell.) Meisn. Leaves

Antinociceptive and anti-inflammatory activities of the Muehlenbeckia platyclada leaves’ ethanol extract were investigated in animal models. The extract (p.o.) reduced the number of abdominal contortions induced by acetic acid by 21.57% (400 mg/kg). After intraplantar injection of formalin, a dose of 400 mg/kg (p.o.) inhibited the time spent paw licking in the first phase (26.43%), while the second phase was inhibited by 10.90 and 36.65% at the doses of 200 and 400 mg/kg, respectively. The extract (p.o.) increased the reaction time on a hot plate at a dose of 400 mg/kg (32.68 and 40.30%) after 60 and 90 minutes of treatment, respectively. The paw edema was reduced by extract (p.o.) at doses of 100 (15.46 and 16.67%), 200 (22.68 and 25.64%) and 400 mg/kg (29.50 and 37.33%) after 3 to 4 h of carrageenan application, respectively. Doses of 100, 200 and 400 mg/kg (p.o.), administered 4 h after the carrageenan injection, reduced the exudate volume (11.28, 21.54 and 45.13%), while leukocyte migration was reduced by 21.21 and 29.70% at the doses of 200 and 400 mg/kg, respectively. These results indicate that the ethanol extract from M. platyclada may constitute a potential target for the discovery of new molecules with antinociceptive and anti-inflammatory activities that can be explored for their therapeutic use

Transmission of Aerosolized Seasonal H1N1 Influenza A to Ferrets

Influenza virus is a major cause of morbidity and mortality worldwide, yet little quantitative understanding of transmission is available to guide evidence-based public health practice. Recent studies of influenza non-contact transmission between ferrets and guinea pigs have provided insights into the relative transmission efficiencies of pandemic and seasonal strains, but the infecting dose and subsequent contagion has not been quantified for most strains. In order to measure the aerosol infectious dose for 50% (aID50) of seronegative ferrets, seasonal influenza virus was nebulized into an exposure chamber with controlled airflow limiting inhalation to airborne particles less than 5 µm diameter. Airborne virus was collected by liquid impinger and Teflon filters during nebulization of varying doses of aerosolized virus. Since culturable virus was accurately captured on filters only up to 20 minutes, airborne viral RNA collected during 1-hour exposures was quantified by two assays, a high-throughput RT-PCR/mass spectrometry assay detecting 6 genome segments (Ibis T5000™ Biosensor system) and a standard real time RT-qPCR assay. Using the more sensitive T5000 assay, the aID50 for A/New Caledonia/20/99 (H1N1) was approximately 4 infectious virus particles under the exposure conditions used. Although seroconversion and sustained levels of viral RNA in upper airway secretions suggested established mucosal infection, viral cultures were almost always negative. Thus after inhalation, this seasonal H1N1 virus may replicate less efficiently than H3N2 virus after mucosal deposition and exhibit less contagion after aerosol exposure

Complex conductivity of soils

The complex conductivity of soils remains poorly known despite the growing importance of this method in hydrogeophysics. In order to fill this gap of knowledge, we investigate the complex conductivity of 71 soils samples (including four peat samples) and one clean sand in the frequency range 0.1 Hz to 45 kHz. The soil samples are saturated with six different NaCl brines with conductivities (0.031, 0.53, 1.15, 5.7, 14.7, and 22 S m21, NaCl, 258C) in order to determine their intrinsic formation factor and surface conductivity. This data set is used to test the predictions of the dynamic Stern polarization model of porous media in terms of relationship between the quadrature conductivity and the surface conductivity. We also investigate the relationship between the normalized chargeability (the difference of in-phase conductivity between two frequencies) and the quadrature conductivity at the geometric mean frequency. This data set confirms the relationships between the surface conductivity, the quadrature conductivity, and the normalized chargeability. The normalized chargeability depends linearly on the cation exchange capacity and specific surface area while the chargeability shows no dependence on these parameters. These new data and the dynamic Stern layer polarization model are observed to be mutually consistent. Traditionally, in hydrogeophysics, surface conductivity is neglected in the analysis of resistivity data. The relationships we have developed can be used in field conditions to avoid neglecting surface conductivity in the interpretation of DC resistivity tomograms. We also investigate the effects of temperature and saturation and, here again, the dynamic Stern layer predictions and the experimental observations are mutually consistent

New Approaches to Clarify Antinociceptive and Anti-Inflammatory Effects of the Ethanol Extract from Vernonia condensata Leaves

The present study was aimed at evaluating the antinociceptive and anti-inflammatory effects of the ethanol extract from Vernonia condensata leaves in animal models, in order to afford a better understanding of these properties. The extract reduced the number of abdominal contortions at doses of 100 (51.00 ± 3.00), 200 (42.00 ± 2.98) and 400 mg/kg (39.00 ± 4.00). In formalin tests, a significant reduction in the licking time (p < 0.01) was observed in the first phase by 25.14 (200 mg/kg = 51.50 ± 4.44) and 31.15% (400 mg/kg = 48.00 ± 4.37). The doses of 100 (43.37 ± 5.15), 200 (34.62 ± 4.16) and 400 mg/kg (28.37 ± 3.98) inhibited (p < 0.001) the second phase. After 60 and 90 min of treatment, a dose of 400 mg/kg (10.13 ± 0.39 and 11.14 ± 1.33, respectively) increased the latency time. Doses of 200 and 400 mg/kg potentiated the sleeping time induced by diazepam, pentobarbital and meprobamate. The extracts (100, 200 and 400 mg/kg) showed anti-inflammatory effects by a decrease in paw edema. The extracts also reduced the exudate volume at the doses of 200 and 400 mg/kg. The leukocyte migration had significant effect (p < 0.001) at doses of 100, 200 and 400 mg/kg. The completion of additional experiments in the investigation of the antinociceptive and anti-inflammatory activities of V. condensata allowed a better understanding of the central and peripheral mechanisms involved

Exhaled Aerosol Transmission of Pandemic and Seasonal H1N1 Influenza Viruses in the Ferret

Person-to-person transmission of influenza viruses occurs by contact (direct and fomites) and non-contact (droplet and small particle aerosol) routes, but the quantitative dynamics and relative contributions of these routes are incompletely understood. The transmissibility of influenza strains estimated from secondary attack rates in closed human populations is confounded by large variations in population susceptibilities. An experimental method to phenotype strains for transmissibility in an animal model could provide relative efficiencies of transmission. We developed an experimental method to detect exhaled viral aerosol transmission between unanesthetized infected and susceptible ferrets, measured aerosol particle size and number, and quantified the viral genomic RNA in the exhaled aerosol. During brief 3-hour exposures to exhaled viral aerosols in airflow-controlled chambers, three strains of pandemic 2009 H1N1 strains were frequently transmitted to susceptible ferrets. In contrast one seasonal H1N1 strain was not transmitted in spite of higher levels of viral RNA in the exhaled aerosol. Among three pandemic strains, the two strains causing weight loss and illness in the intranasally infected ‘donor’ ferrets were transmitted less efficiently from the donor than the strain causing no detectable illness, suggesting that the mucosal inflammatory response may attenuate viable exhaled virus. Although exhaled viral RNA remained constant, transmission efficiency diminished from day 1 to day 5 after donor infection. Thus, aerosol transmission between ferrets may be dependent on at least four characteristics of virus-host relationships including the level of exhaled virus, infectious particle size, mucosal inflammation, and viral replication efficiency in susceptible mucosa