Administration of recombinant factor VIIa decreases blood loss after blunt trauma in noncoagulopathic pigs.

Background: Activated factor VII catalyzes the activation of clotting factors IX and X within the clotting cascade, and has been used clinically to decrease bleeding in patients with hemophilia and other bleeding disorders. Studies suggest the use of recombinant VIIa (rVIIa) may decrease bleeding after injury in the presence of a coagulopathy, but there is conflicting evidence regarding its use in the absence of coagulopathy. This study was performed to determine whether a single dose of rVIIa would reduce blood loss in noncoagulopathic pigs after blunt trauma.

Prokineticin 2 depolarizes paraventricular nucleus magnocellular and parvocellular neurons.

Blind whole-cell patch-clamp techniques were used to examine the effects of prokineticin 2 (PK2) on the excitability of magnocellular (MNC), parvocellular preautonomic (PA), and parvocellular neuroendocrine (NE) neurons within the hypothalamic paraventricular nucleus (PVN) of the rat. The majority of MNC neurons (76%) depolarized in response to 10 nm PK2, effects that were eliminated in the presence of tetrodotoxin (TTX). PK2 also caused an increase in excitatory postsynaptic potential (EPSP) frequency, a finding that was confirmed by voltage clamp recordings demonstrating increases in excitatory postsynaptic current (EPSC) frequency.

Interleukin-1beta depolarizes magnocellular neurons in the paraventricular nucleus of the hypothalamus through prostaglandin-mediated activation of a non selective cationic conductance.

Interleukin-1beta (IL-1beta) is involved in hypothalamic regulation of the neuroimmune response by influencing the synthesis and secretion of corticotropin releasing hormone (CRH), vasopressin (VP) and other stress-related mediators. VP secretion from magnocellular (MNC) neurons of the paraventricular nucleus (PVN) of the hypothalamus at the posterior pituitary and/or median eminence contributes to increasing adrenocorticotropin hormone (ACTH) output and ultimately glucocorticoid release, which then contributes to the stress response. In this study, using whole-cell patch clamp recordings from neurons in a slice preparation of the rat PVN, we show that MNC neurons are also influenced by IL-1beta.

Actions of neuropeptide W in paraventricular hypothalamus: implications for the control of stress hormone secretion.

Neuropeptide W (NPW) is produced in neurons located in hypothalamus and brain stem, and its receptors are present in the hypothalamus, in particular in the paraventricular nucleus (PVN). Intracerebroventricular (ICV) administration of NPW activated, in a dose-related fashion, the hypothalamic-pituitary-adrenal axis, as determined by plasma corticosterone levels in conscious rats but, at those same doses, did not stimulate the release of oxytocin or vasopressin into the peripheral circulation or alter blood pressure or heart rate. The ability of ICV-administered NPW to stimulate the hypothalamic-pituitary-adrenal axis in conscious male rats was blocked by intravenous pretreatment with a corticotropin-releasing hormone antagonist.

Nerve growth factor alters p75 neurotrophin receptor-induced effects in mouse facial motoneurons following axotomy.

The p75 neurotrophin receptor (p75(NTR)) has been implicated as being detrimental for cell survival in facial motoneurons following injury. Although facial motoneurons do not respond to nerve growth factor (NGF) under normal circumstances, this study shows that NGF can interfere with p75(NTR)-mediated cell survival effects on motoneurons following injury. Twenty-five days following injury, the proportion of surviving axotomized neurons in NGF/p75(+/+) mice, which overexpress NGF, was significantly higher compared to wild-type mice, while NGF/p75(-/-) mice, which overexpress NGF but carry two mutated alleles for p75(NTR), had fewer neurons compared to wild-type and p75(-/-) mice, which carry two mutated alleles for p75(NTR), resulting in a lack of functional expression of this receptor.