Subpallidal outputs to the nucleus accumbens and the ventral tegmental area: anatomical and electrophysiological studies

The goal of this study was to investigate the functional organization of the subpallidal-->accumbens direct and indirect feedback loops by both anatomical and electrophysiological methods. The results of the dextran-conjugated rhodamine injections into the subpallidal area has shown three distinct projections: (1) a substantial pathway from the subpallidal area to the ventral tegmental area, (2) a more diffuse rostral projection from the subpallidal area to the core area of the nucleus accumbens, and (3) a sparse pathway projecting rostrodorsally from the subpallidal area toward the thalamic regions. Electrical or chemical stimulation of the subpallidal region, which was studied by the axonal tracer, evoked inhibitory responses in the majority (60 and 80%, respectively) of the accumbens and ventral tegmental area neurons in a standard extracellular recording study. Less than 1/3 of the accumbens or ventral tegmental area cells showed an increase in the mean firing rate. The majority (77.5%) of all responded neurons had a latency of less than 10 ms. Furthermore, injection of glutamate into the subpallidal area not only altered the firing pattern of the accumbens neurons, but also attenuated their excitatory responses elicited by the electrical stimulation of the ventral subiculum. Our results indicate that the subpallidal area plays a predominantly inhibitory role in the ventral tegmental area-accumbens-subpallidal circuitry, presumably by its GABAergic projections, and may also modulate subicular input into the nucleus accumbens.     

Distraction osteogenesis for lengthening of the hard palate: Part I. A possible new treatment concept for velopharyngeal incompetence. Experimental study in dogs

Many procedures have been described to correct velopharyngeal incompetence. Significant complications can occur, and the results may not be satisfactory. If the short soft palate has satisfactory muscle function and if it could be moved toward the posterior pharyngeal wall by distraction osteogenesis of the hard palate, an entirely new concept of treatment for velopharyngeal incompetence would be available. The object of the present study was to explore the possibility of osteogenesis occurring in the hard palate in dogs after gradual distraction (callus distraction). Six adult, mix-bred dogs were anesthetized, and the palatal mucosa was elevated. A midpalatal transverse osteotomy and two lateral osteotomies were performed. Tantalum bone markers for cephalometric analysis were placed, and an individually fabricated, orthodontic-like distraction device with an expansion screw in the sagittal direction was inserted. The device was stabilized on the premolars and fixed to the palatal bone with titanium miniscrews. Gradual distraction began after a latency period of 10 to 18 days. The rate of the distraction varied from 0.25 to 0.75 mm per day. The device was left in place for 6 to 8 weeks after expansion to allow for bony consolidation. Assessment was by direct examination, cephalograms, computed tomography, and histology with bone labeling. Impressions of the jaws were taken preoperatively and after device removal to examine plaster cast changes in the dental occlusion. Cephalometric and computed tomographic scan analysis demonstrated a distraction of up to 8 mm. All gaps were filled with de novo osteogenesis. Comparison of the plaster casts revealed no change in the occlusion. At 1 month after distraction, the computed tomographic scan showed the first signs of ossification of the experimental gap from the anterior and posterior bone ends. After 4.5 months ossification was almost complete with a small translucent zone in the middle of the experimental gap. After 7 months ossification was complete.     

Should diastasis recti be corrected?

From theoretical considerations animals with a higher protein-fat ratio in the body should have a higher maintenance energy requirement (MEm). The literature on this problem shows a non-uniform picture with deviating results. From the results of a series of experiments it is possible to compare the heat production (HP) of male and female animals of the Vietnamese Sway-back breed pigs which vary quite widely in their body composition. The protein-fat ratio was 1.2 for the male and 0.2 for the female animals. In the experiments 4 male and 4 female animals in the live weight range of 20-33 kg and 33-42 kg, respectively, were involved. The HP measurements were carried out in climatized respiration chambers on two levels of energy intake at ambient temperatures of 6 degrees C, 12 degrees C, 18 degrees C, 24 degrees C, 30 degrees C, and 35 degrees C. The dependence of HP on the ambient temperature has been described by a cubic regression function. Thermoneutral temperatures are lower in the female animals caused by the better insulation effect of the backfat. The difference in HP which was expected by the large difference in body composition, was not found. The absolute protein mass determined the correlation to HP. Certainly the difference increased after lowering the ambient temperature. The influence of different factors on HP is discussed.     

A versatile facility for laboratory studies of viscoelastic and poroelastic behaviour of rocks

Novel laboratory equipment has been modified to allow both torsional and flexural oscillation measurements at sub-microstrain amplitudes, thereby providing seismic-frequency constraints on both the shear and compressional wave properties of cylindrical rock specimens within the linear regime. The new flexural mode capability has been tested on experimental assemblies containing fused silica control specimens. Close consistency between the experimental data and the results of numerical modelling with both finite-difference and finite-element methods demonstrates the viability of the new technique. The capability to perform such measurements under conditions of independently controlled confining and pore-fluid pressure, with emerging strategies for distinguishing between local (squirt) and global (specimen-wide) fluid flow, will have particular application to the study of frequency-dependent seismic properties expected of cracked and fluid-saturated rocks of the Earth's upper crust.     

Gene Expression Analyses Support Fallopian Tube Epithelium as the Cell of Origin of Epithelial Ovarian Cancer

Folate receptor alpha (FOLR1/FRA) is reported to be overexpressed in epithelial ovarian cancers (EOC), especially the serous histotype. Further, while dysregulation of the folate-dependent 1-carbon cycle has been implicated in tumorogenesis, little is known relative to the potential mechanism of action of FOLR1 expression in these processes. We therefore investigated the expression of FOLR1, other folate receptors, and genes within the 1-carbon cycle in samples of EOC, normal ovary and fallopian tube on a custom TaqMan Low Density Array. Also included on this array were known markers of EOC such as MSLN, MUC16 and HE4. While few differences were observed in the expression profiles of genes in the 1-carbon cycle, genes previously considered to be overexpressed in EOC (e.g., FOLR1, MSLN, MUC16 and HE4) showed significantly increased expression when comparing EOC to normal ovary. However, when the comparator was changed to normal fallopian tube, these differences were abolished, supporting the hypothesis that EOC derives from fallopian fimbriae and, further, that markers previously considered to be upregulated or overexpressed in EOC are most likely not of ovarian origin, but fallopian in derivation. Our findings therefore support the hypothesis that the cell of origin of EOC is tubal epithelium.     

Heterogeneous Catalytic Esterification of ω-Sulfhydryl Fatty Acids: Avoidance of Thioethers,Thioesters, and Disulfides

Two mesoporous silicas functionalized with propylsulfonic (SBA-15-PSA) and arenesulfonic (SBA-15-ASA) acid groups, and a highly acidic, functionalized styrene divinylbenzene copolymer ion exchange resin (Amberlyst-15) were examined for their ability to catalyze the ethanolic esterification of the ω-sulfhydryl fatty acid, 11-mercaptoundecanoic acid (MUA), without catalyzing unwanted side reactions at the sulfhydryl group. All three solid acid catalysts catalyzed the MUA esterification in excess ethanol. The activation energy for the catalytic esterifications were determined from 50 to 75 °C, resulting in apparent E _a of 54, 71, and 59 kJ/mol for SBA-15-PSA, SBA-15-ASA, and Amberlyst-15, respectively. GC–MS analysis determined that all three catalysts produced near quantitative conversion of MUA to its ethyl ester with very little reactivity towards the sulfhydryl group. This was a marked improvement over the esterifications catalyzed by sulfuric and p-toluenesulfonic acids which produced thioethers and disulfide side products. The MUA ethyl ester synthesis was demonstrated on a gram scale at 70 °C catalyzed by Amberlyst-15, and the desired product was isolated in 80% yield at >95% purity with a minimum of purification.     

Non-aqueous titration of the acidic groups in coals: a warning!

Non-aqueous potentiometric titration using ethylenediamine as a solvent and sodium aminoethoxide as a titrant has been shown to be reliable for the estimation of total acidity only when the substrate is completely dissolved in the solvent.     

Tuning of ultraviolet-curable ink printability via in situ ultraviolet irradiation during direct ink write applications

Direct ink write deposition facilitates line-by-line extrusion of inks spanning wide viscoelastic ranges. Following deposition, post processing technologies permit tuning of the extrudate's material property characteristics—ultraviolet (UV) irradiation, facilitating the photopolymerization of UV-reactive catalyst solutions, permits targeted modification of the extrudate's microstructure and in situ tuning of extrudate macrostructure. This report analyzes the morphological, rheological, and microstructural property relationships governing the printability, and processivity, of extruded UV-curable resin inks for delineation of sufficiency and optimization of ink printability utilizing direct ink write technologies. A design-of-experiments approach is implemented to quantify significance regarding an extrudate's dimensional response to extrusion parameter variation and in situ processing parameters, identifying proportionally of nozzle velocity, nozzle height, and UV irradiation exposure with extrudate aspect ratio, reflected by respective maximum extrudate aspect ratio increases of 158% and 109%, regarding 121 and 123K resin inks. Finally, the relationship between extrudate morphology and microstructure variation was assessed via dielectric cure monitoring, whereby an extrudate's ion viscosity was calculated in relation to its rheological modulus, reflecting the relationship between an extrudate's morphology, rheological response, and printability, regarding its microstructural variation.     

Pilocarpine‐loaded poly(DL‐lactic‐co‐glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response

The poor corneal residence time of pilocarpine, an alkaloid extracted from the leaves of the Jaborandi plant, limits its ocular application. The aim of this study was to develop, characterize, and evaluate the potential of pilocarpine entrapped by poly(DL ‐lactic‐co‐glycolic acid) (PLGA) nanoparticle carriers for ocular drug delivery. Pilocarpine‐loaded nanoparticles were prepared with a double‐emulsion (water in oil in water) method and characterized with transmission electron microscopy and X‐ray diffraction analysis. The nanoparticles exhibited an average size of 82.7 nm with an encapsulation efficiency of 57%. Stability studies showed the absence of agglomeration and constancy in the amount of drug entrapped; this indicated the solidity of these particles for long‐term use. The in vitro release studies conducted in simulated tear fluid showed the sustained release of pilocarpine. In vivo evaluation of the nanoparticles was done in a rabbit model with a miosis assay and compared to an equal dose of commercially available eye drops of pilocarpine (Pilocar drops). The in vivo miosis studies showed that the duration of miotic response increased by 40% for the nanoparticles and produced an almost 68% increase in total miotic response when compared to the eye drops. In conclusion, this study clearly demonstrated the potential of pilocarpine‐loaded PLGA nanoparticles for multiplying the therapeutic effect of ophthalmic drug delivery with enhanced bioavailability and pharmacological response. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012