Modulation of P2 auditory-evoked responses by the spectral complexity of musical sounds

We investigated whether N1 and P2 auditory-evoked responses are modulated by the spectral complexity of musical sounds in pianists and non-musicians. Study participants were presented with three variants of a C4 piano tone equated for temporal envelope but differing in the number of harmonics contained in the stimulus. A fourth tone was a pure tone matched to the fundamental frequency of the piano tones. A simultaneous electroencephalographic/magnetoencephalographic recording was made. P2 amplitude was larger in musicians and increased with spectral complexity preferentially in this group, but N1 did not. The results suggest that P2 reflects the specific features of acoustic stimuli experienced during musical practice and point to functional differences in P2 and N1 that relate to their underlying mechanisms.     

The therapeutic potential of stem cells in the treatment of craniofacial abnormalities

Anomalies associated with the vertebrate head and face account for a third of all reported major birth defects. Of the principle cell populations that participate in formation of the craniofacial complex, the neural crest is central, generating much of the peripheral nervous system and constituting the predominant connective tissue-forming mesenchyme of the facial skeleton. Many craniofacial anomalies are, therefore, largely attributed to defects in neural crest cell development. Neural crest cells exhibit many of the features of stem cells; they are multipotent, remarkably plastic and have a limited capacity for self-renewal. This article will review recent studies that demonstrate the ability of stem cells to generate neural crest cell populations that form appropriate neural crest derivatives in the developing craniofacial complex, and will discuss the potential application for stem cells in the treatment of craniofacial disorders.     

Anxiolytic-like effects of the corticotropin-releasing factor1 (CRF1) antagonist DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] administered acutely or chronically at doses occupying central CRF1 receptors in rats

Corticotropin-releasing factor(1) (CRF(1)) antagonists may be effective in the treatment of anxiety disorders with fewer side effects compared with classic benzodiazepines. The behavioral effects of DMP904 [4-(3-pentylamino)-2,7-dimethyl-8-(2-methyl-4-methoxyphenyl)-pyrazolo-[1,5-a]-pyrimidine] and its effects on the hypothalamic-pituitary-adrenal (HPA) axis were related to its levels in plasma and estimated occupancy of central CRF(1) receptors. DMP904 (10-30 mg/kg, p.o.) and alprazolam (10 mg/kg, p.o.) increased time spent in open arms of an elevated-plus maze. In addition, acutely or chronically (14 days) administered DMP904 (1.0-30 mg/kg, p.o.) and acute alprazolam (1.0-3.0 mg/kg, p.o.) significantly reduced exit latency in the defensive withdrawal model of anxiety in rats, suggesting that tolerance may not develop to the anxiolytic-like effects of DMP904 in this model of anxiety. Acutely, DMP904 reversed the stress-induced increase in plasma corticosterone levels in defensive withdrawal at doses of 3.0 mg/kg and higher. These doses also resulted in levels of DMP904 in plasma similar to (for anxiolytic-like effects) or 4-fold higher (for effects on the HPA axis) than the in vitro IC(50) value for binding affinity at CRF(1) receptors and greater than 50% occupancy of CRF(1) receptors. Unlike alprazolam, DMP904 did not produce sedation, ataxia, or chlordiazepoxide-like subjective effects (as measured by locomotor activity, rotorod performance, and chlordiazepoxide discrimination assays, respectively) at doses at least 3-fold higher than anxiolytic-like doses. In conclusion, anxiolytic-like effects and effects on the stress-activated HPA axis of DMP904 in the defensive withdrawal model of anxiety required 50% or greater occupancy of central CRF(1) receptors. This level of CRF(1) receptor occupancy resulted in fewer motoric side effects compared with classic benzodiazepines.     

Synthesis, structure-activity relationships, and in vivo properties of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones as corticotropin-releasing factor-1 receptor antagonists

Corticotropin releasing factor (CRF) is the primary regulator of the hypothalamus-pituitary-adrenal (HPA) axis, coordinating the endocrine, behavioral, and autonomic responses to stress. It has been postulated that small molecules that can antagonize the binding of CRF1 to its receptor may serve as a treatment for anxiety-related and/or affective disorders. Members within a series of 3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-ones, exemplified by compound 2 (IC50 = 0.70 nM), were found to be very potent antagonists of CRF1. Compound 8w showed high CRF1 receptor binding affinity and was examined further in vivo. The compound was efficacious in a defensive withdrawal model of anxiety in rats and had a long half-life and reasonable oral bioavailability in dog pharmacokinetic studies.     

Pb(II) distributions at biofilm-metal oxide interfaces

The distribution of aqueous Pb(II) sorbed at the interface between Burkholderia cepacia biofilms and hematite (alpha-Fe(2)O(3)) or corundum (alpha-Al(2)O(3)) surfaces has been probed by using an application of the long-period x-ray standing wave technique. Attached bacteria and adsorbed organic matter may interfere with sorption processes on metal oxide surfaces by changing the characteristics of the electrical double layer at the solid-solution interface, blocking surface sites, or providing a variety of new sites for metal binding. In this work, Pb L(alpha) fluorescence yield profiles for samples equilibrated with 10(-7) to 10(-3.8) M Pb(II) were measured and modeled to determine quantitatively the partitioning of Pb(II) at the biofilm-metal oxide interface. Our data show that the reactive sites on the metal oxide surfaces were not passivated by the formation of a monolayer biofilm. Instead, high-energy surface sites on the metal oxides form the dominant sink for Pb(II) at submicromolar concentrations, following the trend alpha-Fe(2)O(3) (0001) > alpha-Al(2)O(3) (1102) > alpha-Al(2)O(3) (0001), despite the greater site density within the overlying biofilms. At [Pb] > 10(-6) M, significant Pb uptake by the biofilms was observed.     

Respiratory function after repair of congenital diaphragmatic hernia

Respiratory function studies were carried out in 22 infants who had successful repair of diaphragmatic herniae of the Bochdalek type. Thoracic gas volume was initially reduced in only 3 of these, but subsequent studies showed that improvement occurred. There were no consistent abnormalities in either dynamic compliance or mean pulmonary conductance. This is evidence that there is rapid adaptation which compensates for any alteration in the parenchymatous tissue in the lungs or abnormalities in the bronchial tree in infants soon after the repair of congenital diaphragmetic herniae. Further studies are necessary to determine the changes in these lungs with growth.     

Management of severe ischemia of the foot secondary to occlusive vascular disease.

One hundred patients, 111 limbs, with gangrene of the lower extremity were initially treated with lumbar sympathectomy. Lumbar sympathectomy appears to be most beneficial in the management of gangrene of the toe with a limb salvage rate of 75 per cent. The best results were seen when only one toe, not the big toe, was involved. Limb salvage dropped to 38 per cent for gangrene of the foot, and with gangrene of the leg, lumbar sympathectomy had no affect. The presence of diabetes had no affect on limb salvage for gangrene of the toe but did have an apparent affect on limb salvage for gangrene of the foot. Sympathectomy appeared to aid in stump healing, with 77 per cent of the amputations done not requiring revision to a higher level. Results of our experience appear to indicate that, for patients presenting with gangrene of the toes or forefoot who are not candidates for reconstructive arterial procedures, lumbar sympathectomy as an initial operative procedure should be given serious consideration.