TLRs are highly conserved pathogen recognition receptors. As a result, TLR4-deficient C3H/HeJ mice are highly susceptible to Gram-negative sepsis. We have previously demonstrated that tolerance induced by bacterial lipoprotein (BLP) protects wild-type mice against polymicrobial sepsis-induced lethality. In this study, we assessed whether pretreatment of C3H/HeJ mice with BLP could induce resistance to a subsequent Gram-negative Salmonella typhimurium infection. Pretreatment with BLP resulted in a significant survival benefit in TLR4-deficient C3H/HeJ mice (p < 0.0002 vs control C3H/HeJ) after challenge with live S. typhimurium (0.25 × 106 CFU/mouse). This survival benefit was associated with enhanced bacterial clearance from the circulation and in the visceral organs (p < 0.05 vs control C3H/HeJ). Furthermore, pretreatment with BLP resulted in significant increases in complement receptor type 3 (CR3) and FcγIII/IIR expression on polymorphonuclear neutrophils (PMNs) and macrophages (p < 0.05 vs control C3H/HeJ). There was impaired bacterial recognition and phagocytosis in TLR4-deficient mice compared with wild-type mice. However, a significant augmented uptake, ingestion, and intracellular killing of S. typhimurium by PMNs and peritoneal macrophages was evident in BLP-pretreated C3H/HeJ mice (p < 0.05 vs control C3H/HeJ). An up-regulation of inducible NO synthase and increased production of intracellular NO were observed in peritoneal macrophages from BLP-pretreated C3H/HeJ mice (p < 0.05 vs control C3H/HeJ). Depletion of PMNs did not diminish the beneficial effects of BLP with regard to both animal survival and bacterial clearance. These results indicate that BLP, a TLR2 ligand, protects highly susceptible TLR4-deficient mice from Gram-negative sepsis via enhanced bacterial clearance.
With 3 plates in the text) Golden moles (Chrysochloridae) are fossorial mammals known to have unusual mallei. The aim of this study was to describe and quantify aspects of the auditory morphology of golden moles in order to determine their systematic and functional implications. Observations were made on skeletal material as well as histological sections. The results of this study do not support the separation of the genus Culcochloris from Amblysomus. It was found that the morphology shared by all the studied genera is indicative of specialization for hearing low frequency sound. The tympanic membrane to stapes footplate ratios, ossicular lever arm ratios and incudomallear joint morphology suggest low frequency specializations in genera with small mallear heads and high frequency specializations in genera with large mallear heads. However, the size and degree of trabeculation of the tympanic cavity are not consistent with this result. It is proposed that all golden moles are low frequency hearers with differences in their range of sensitivity according to how much time they spend foraging above ground.
A 50-year-old gentleman was admitted under our services after a fall onto his right side. He sustained an inter-trochanteric fracture of his right femur with reverse obliquity pattern and a displaced fracture of the surgical neck of his right humerus. He had a history of alcohol abuse, but his past medical history was otherwise non-contributory. He underwent dynamic hip screw fixation of his right femur and Polarus nail insertion of his right humeral fracture. His post-operative stay was complicated by delerium tremens and a below knee DVT which required treatment with warfarin. Subsequent radiographs demonstrated stable medial displacement of the femoral shaft. Following stabilisation of his medical condition, he was discharged home on crutch walking.He was re-admitted seven months later with severe pain in his right groin radiating to the anterior aspect of his right thigh and weakness of his right leg. On examination, he was found to have a large nonexpansile pulsatile mass in his right groin. Arteriography was performed which confirmed the presence of a large pseudoaneurysm arising from the profunda femoris artery. He was also noted to have an ilio-femoral thrombosis and a Greenfield filter was therefore inserted. Attempted embolisation of his pseudoaneurysm failed. He then underwent surgical repair of his pseudoaneurysm.Post-operatively he was unable to straight leg raise and EMG studies demonstrated a severe femoral neuropathy. He was discharged form hospital on crutch walking (Figs. 1-3).
Co-administration of taurolidine with high-dose rIL-2 in stage IV melanoma patients appears to greatly enhance the tolerability of this regime without diminishing its therapeutic value.
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