Association between the Depth of Sevoflurane or Propofol Anesthesia and the Incidence of Emergence Agitation in Children: A Single-Center Retrospective Study.

In the present study, we investigated the hypothesis that the depth of general anesthesia affects emergence agitation (EA) in children in the early postanesthetic period. We retrospectively examined male and female children (aged 1-9 years) who underwent ambulatory surgery that lasted < 2 h. Various parameters, including the modified Yale Preoperative Anxiety Score (mYPAS) before anesthesia induction, the Pediatric Anesthesia Emergence Delirium (PAED) score at recovery time, and the value of the patient state index (PSI), were extracted from our electronic anesthesia database.

Chronic allergic lung inflammation negatively influences neurobehavioral outcomes in mice.

Background: Asthma is a major public health problem worldwide. Emerging data from epidemiological studies show that allergies and allergic diseases may be linked to anxiety, depression and cognitive decline. However, little is known about the effect of asthma, an allergic lung inflammation, on cognitive decline/behavioral changes.

Reduced allergic lung inflammation and airway responsiveness in mice lacking the cytoskeletal protein gelsolin.

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore, reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation of the inflammatory response.

Ginger and its bioactive component 6-shogaol mitigate lung inflammation in a murine asthma model.

Asthma, a common disorder associated with airway inflammation and hyperresponsiveness, remains a significant clinical burden in need of novel therapeutic strategies. Patients are increasingly seeking complementary and alternative medicine approaches to control their symptoms, including the use of natural products. Ginger, a natural product that we previously demonstrated acutely relaxes airway smooth muscle (ASM), has long been reported to possess anti-inflammatory properties, although a precise mechanistic understanding is lacking.

Attenuation of murine and human airway contraction by a peptide fragment of the cytoskeleton regulatory protein gelsolin.

We have previously reported that mice genetically deficient in the actin binding protein gelsolin exhibit impaired airway smooth muscle (ASM) relaxation. Primary cultured ASM cells from these mice demonstrate enhanced inositol triphosphate (IP) synthesis and increased intracellular calcium in response to G-coupled agonists. We hypothesized that this was due to increased intracellular availability of unbound phosphatidylinositol 4,5-bisphosphate (PIP), based on the fact that gelsolin contains a short peptide region that binds PIP, presumably making it a less available substrate.

Calreticulin inhibits inflammation-induced osteoclastogenesis and bone resorption.

Osteoclasts play key roles in bone remodeling and pathologic osteolytic disorders such as inflammation, infection, bone implant loosening, rheumatoid arthritis, metastatic bone cancers, and pathological fractures. Osteoclasts are formed by the fusion of monocytes in response to receptor activators of NF-κB-ligand (RANKL) and macrophage colony stimulating factor 1 (M-CSF). Calreticulin (CRT), a commonly known intracellular protein as a calcium-binding chaperone, has an unexpectedly robust anti-osteoclastogenic effect when its recombinant form is applied to osteoclast precursors in vitro or at the site of bone inflammation externally in vivo.

Dexmedetomidine's inhibitory effects on acetylcholine release from cholinergic nerves in guinea pig trachea: a mechanism that accounts for its clinical benefit during airway irritation.

Background: Airway instrumentation can evoke upper airway reflexes including bronchoconstriction and cough which can cause serious complications including airway trauma, laryngospasm or bronchospasm which may in turn lead to difficulty with ventilation and hypoxemia. These airway events are mediated in part by irritant-induced neuronal modulation of airway tone and cough responses. We investigated whether the commonly used anesthetic agents dexmedetomidine, lidocaine or remifentanil attenuated neuronal and airway smooth muscle responses in the upper airways of guinea pigs.

Impaired Relaxation of Airway Smooth Muscle in Mice Lacking the Actin-Binding Protein Gelsolin.

Diverse classes of ligands have recently been discovered that relax airway smooth muscle (ASM) despite a transient increase in intracellular calcium concentrations ([Ca]). However, the cellular mechanisms are not well understood. Gelsolin is a calcium-activated actin-severing and -capping protein found in many cell types, including ASM cells.

CA-074Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c-FOS signaling pathways.

The osteoclast is an integral cell of bone resorption. Since osteolytic disorders hinge on the function and dysfunction of the osteoclast, understanding osteoclast biology is fundamental to designing new therapies that curb osteolytic disorders. The identification and study of lysosomal proteases, such as cathepsins, have shed light on mechanisms of bone resorption.

MMP-9 levels in elderly patients with cognitive dysfunction after carotid surgery.

Approximately 25% of elderly patients scheduled for carotid endarterectomy (CEA) develop post-operative cognitive dysfunction (CD). We tested the hypothesis that the plasma levels of matrix metalloproteinase 9 (MMP-9) are predictive of moderate to severe CD after CEA. A total of 73 patients were prospectively enrolled in this Institutional Review Board-approved study.

GRINL1A colocalizes with N-methyl D-aspartate receptor NR1 subunit and reduces N-methyl D-aspartate toxicity.

We hypothesized that proteins from the GRINL1A complex transcription unit called Gcom proteins modulate glutamatergic neurotransmission through interaction with the NR1 subunit of the N-methyl D-aspartate (NMDA) receptor. Cotransfection of hemagglutinin-tagged Gcom1 (GRINL1A combined transcript 1) and NR1 cDNAs into HEK293 cells revealed overlapping fluorescent signals in the plasma membrane. Coimmunoprecipitation studies demonstrated reciprocal coimmunoprecipitation from rat brain protein isolates, suggesting an interaction between GRINL1A proteins and the NMDA receptor.

beta-Adrenoceptor blockers protect against staurosporine-induced apoptosis in SH-SY5Y neuroblastoma cells.

The beta-adrenoceptor blockers exhibit a well-characterized anti-apoptotic property in the heart and kidney while less is known about the effect of this class of drugs on neuronal apoptosis. We studied the effects of three beta-adrenoceptor blockers propranolol (1-(isoproplyamino)-3-(naphthalene-1-yloxy)propan-2-ol), atenolol (2-[4-[2-hydroxy-3-(1-methylethylamino)propoxyl]phenyl]ehanamide), and ICI 118551 (1-[2,3-(dihydro-7-methyl-1H-iden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), against staurosporine-induced apoptosis in SH-SY5Y human neuroblastoma cells. Staurosporine increased caspase 3-like activity, DNA fragmentation, PARP cleavage, and the number of TUNEL positive cells consistent with the induction of apoptosis.

Connexin 43 confers resistance to hydrogen peroxide-mediated apoptosis.

The current study aimed to understand the anti-apoptotic effect of overexpressed gap junction forming protein connexin (Cx) 43 in C6 glioma cells. C6 cells exposed to hydrogen peroxide (H2O2) or staurosporine demonstrated morphological and biochemical changes consistent with apoptosis, whereas C6 cells expressing Cx43 demonstrated relative resistance to H2O2, but not to staurosporine. This selective protection against H2O2 was due to inhibition of caspase-3 activation in Cx43 expressing cells.

p38 mitogen-activated protein kinase independent SB203580 block of H2O2-induced increase in GABAergic mIPSC amplitude.

Hydrogen peroxide may serve as a diffusible intermediary messenger under physiological and pathophysiological conditions. H2O2 (1 mM) increased the amplitude of GABAergic miniature inhibitory postsynaptic currents in substantia gelatinosa of the spinal cord. This effect of H2O2 was reversed by the p38 antagonist SB203580, but not by the extracellular signal-regulated kinase 1/2 antagonist PD98059, or the Jun N-terminal kinase antagonist, SP600125.

Hydrogen peroxide increases GABAergic mIPSC through presynaptic release of calcium from IP3 receptor-sensitive stores in spinal cord substantia gelatinosa neurons.

GABAergic interneurons of the spinal cord substantia gelatinosa regulate the transmission of nociceptive information. Hydrogen peroxide (H2O2) is likely a diffusible messenger contributing to the development of long-lasting pathological pain states after nerve injury. In this study, we examined the presynaptic effects of H2O2 on the inhibitory interneurons of mouse substantia gelatinosa (SG) using whole-cell patch-clamp recordings from spinal cord slices.

Cardiac mitochondrial connexin 43 regulates apoptosis.

Connexin 43 (Cx43) is thought to be present largely in the plasma membrane and its function solely to provide low resistance electrical connection between myocytes. A recent report suggested the presence of Cx43 in the mitochondria as well. We confirmed the presence of Cx43 in the mitochondria isolated from adult rat ventricles with the Cx43 immunoreactivity fractionating to the outer mitochondrial membrane.

Short hairpin RNA-mediated selective knockdown of NaV1.8 tetrodotoxin-resistant voltage-gated sodium channel in dorsal root ganglion neurons.

Background: Voltage-gated sodium channels comprise a family of closely related proteins, each subserving different physiologic and pathologic functions. NaV1.8 is an isoform of voltage-gated sodium channel implicated in the pathogenesis of inflammatory and neuropathic pain, but currently, there is no isoform-specific inhibitor of any voltage-gated sodium channels.