The use of both methods was more informative than the use of only one of these methods. Thus combining CTT and IRT appears to be a valuable tool in the development of measures.”
“ObjectiveThe pathobiology of prostate cancer (PCa)-induced bone pain (PCIBP) has both inflammatory and neuropathic components. Previously, we showed that small molecule angiotensin II type 2 receptor (AT(2)R) antagonists with >1,000-fold selectivity over the angiotensin II type 1 receptor produced dose-dependent analgesia in a rat model of neuropathic pain. Here, we click here assessed the analgesic efficacy and mode of action of the
AT(2)R antagonist, EMA200, in a rat model of PCIBP.
MethodsAt 14-21 days after unilateral intratibial injection of AT3B PCa cells, rats exhibiting hindpaw hypersensitivity received single intravenous bolus doses of EMA200 (0.3-10mg/kg) or vehicle, and analgesic efficacy was assessed. The mode of action was investigated using immunohistochemical, Western blot, and/or molecular biological methods in lumbar dorsal root ganglia (DRGs) removed from drug-naive and EMA200-treated PCIBP rats relative to sham-control rats.
ResultsIntravenous bolus doses of EMA200 produced dose-dependent analgesia in PCIBP rats.
Lumbar DRG levels of angiotensin II, nerve growth factor (NGF), tyrosine kinase A (TrkA), phospho-p38 mitogen-activated protein Selleckchem NCT-501 kinase (MAPK), and phospho-p44/p42 MAPK, but not the AT(2)R, were increased significantly (P<0.05) in PCIBP rats, c.f. the corresponding levels for sham controls. EMA200 produced
analgesia in PCIBP rats by reducing elevated angiotensin II levels in the lumbar DRGs to attenuate augmented angiotensin II/AT(2)R signaling. This in turn reduced augmented BI 6727 nmr NGF/TrkA signaling in the lumbar DRGs. The net result was inhibition of p38 MAPK and p44/p42 MAPK activation.
ConclusionSmall molecule AT(2)R antagonists are worthy of further investigation as novel analgesics for relief of intractable PCIBP and other pain types where hyperalgesia worsens symptoms.”
“Aedes albopictus, a mosquito originally from Southeast Asia, is considered to be one of the main vectors of dengue fever, yellow fever and other arboviruses. We examined the genetic variability and population structure of 68 individuals of Ae. albopictus collected from five neighborhoods of the city of Manaus, based on the mitochondrial gene coding for NADH dehydrogenase subunit 5 (ND5). Two haplotypes were found, separated by a single mutational event (T. C), with extremely low levels of genetic variability (h = 0.187 +/- 0.059; pi = 0.00044 +/- 0.00014). Based on AMOVA, we concluded that most of the variation (99.08%) occurred within populations, though the levels of variation were not significant.