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The phase reconstruction process in digital holographic microscopy involves a trade-off between the phase error and the high-spatial-frequency components. In this reconstruction process, if the narrow region of the sideband is windowed in the Fourier domain, the phase error from the DC component will be reduced, but the high-spatial-frequency components will be lost. However, if the wide region is windowed, the 3D profile will include the high-spatial-frequency components, but the phase error will increase. To solve this trade-off, we propose the high-variance pixel averaging method, which uses the variance map of the reconstructed depth profiles of the windowed sidebands of different sizes in the Fourier domain to classify the phase error and the high-spatial-frequency components. Our proposed method calculates the average of the high-variance pixels because they include the noise from the DC component. In addition, for the nonaveraged pixels, the reconstructed phase data created by the spatial frequency components of the widest window are used to include the high-spatial-frequency components. We explain the mathematical algorithm of our proposed method and compare it with conventional methods to verify its advantages.

Accurate identification of active sites is critical for elucidating catalytic reaction mechanisms and developing highly efficient and selective electrocatalysts. Herein, we report the atomic-level identification of active sites using atomically well-defined gold nanoclusters (Au NCs) Au 25 , Au 38 , and Au 144 as model catalysts in the electrochemical CO 2 reduction reaction (CO 2 RR). The studied Au NCs exhibited remarkably high CO 2 RR activity, which increased with increasing NC size. Electrochemical and X-ray photoelectron spectroscopy analyses revealed that the Au NCs were activated by removing one thiolate group from each staple motif at the beginning of CO 2 RR. In addition, density functional theory calculations revealed higher charge densities and upshifts of d -states for dethiolated Au sites. The structure-activity properties of the studied Au NCs confirmed that dethiolated Au sites were the active sites and that CO 2 RR activity was determined by the number of active sites on the cluster surface.

Learner corpus studies using syntactic complexity as a construct for characterizing learner proficiency have found that higher proficiency permits learners to produce more complex syntactic structures. However, the majority of previous studies have focused on writing, almost exclusively with adult second language (L2) learners. Given the fundamentally different mechanisms underlying speaking and writing activities, this study investigated (a) how different processes involved in writing and speaking performance affect child L2 learners? sentence production, and (b) whether syntactic complexity is a better predictor of proficiency in a particular production type. To this end, we analyzed syntactic complexity for written and spoken corpora supplied by native Korean-speaking child learners of English using 7 syntactic complexity indices. Results showed that learners used longer sentences, more subordination, more verb phrases per T?unit, and less coordination in writing than in speaking. In addition, a prediction model fitted to the written corpus explained more of the variance in proficiency scores than a model based on the spoken corpus. These findings indicate that the different processes underlying writing and speaking influence the way that beginning-level child L2 learners produce sentences in writing and speaking tasks.

Hierarchical self-assembly of building blocks over multiple length scales is ubiquitous in living organisms. Microtubules are one of the principal cellular components formed by hierarchical self-assembly of nanometer-sized tubulin heterodimers into protofilaments, which then associate to form micron-length-scale, multi-stranded tubes. This peculiar biological process is now mimicked with a fully synthetic molecule, which forms a 1:1 host-guest complex with cucurbit[7]uril as a globular building block, and then polymerizes into linear poly-pseudorotaxanes that associate laterally with each other in a self-shape-complementary manner to form a tubular structure with a length over tens of micrometers. Molecular dynamic simulations suggest that the tubular assembly consists of eight poly-pseudorotaxanes that wind together to form a 4.5 nm wide multi-stranded tubule.

Tonic extrasynaptic GABAA receptor (GABAA R) activation is under the tight control of tonic GABA release from astrocytes to maintain the brain's excitation/inhibition (E/I) balance; any slight E/I balance disturbance can cause serious pathological conditions including epileptic seizures. However, the pathophysiological role of tonic GABA release from astrocytes has not been tested in epileptic seizures. Here, we report that pharmacological or genetic intervention of the GABA-permeable Bestrophin-1 (Best1) channel prevented the generation of tonic GABA inhibition, disinhibiting CA1 pyramidal neuronal firing and augmenting seizure susceptibility in kainic acid (KA)-induced epileptic mice. Astrocyte-specific Best1 over-expression in KA-injected Best1 knockout mice fully restored the generation of tonic GABA inhibition and effectively suppressed seizure susceptibility. We demonstrate for the first time that tonic GABA from reactive astrocytes strongly contributes to the compensatory shift of E/I balance in epileptic hippocampi, serving as a good therapeutic target against altered E/I balance in epileptic seizures.

Pleural effusion is a common complication in patients with chronic kidney disease (CKD), particularly in those with end‐stage renal disease (ESRD). Transudative pleural effusion is commonly caused by hypervolemia, whereas exudative pleural effusion can be caused by infections such as tuberculosis, malignancies, and connective tissue diseases.1, 2, 3, 4, 5 Uremic pleuritis, which is a diagnosis of exclusion and results from inflammation of the visceral and parietal pleura, can also cause exudative pleural effusion.1, 6, 7, 8, 9 Although the pathogenesis of uremic pleuritis remains uncertain, it has primarily been reported in patients with ESRD receiving dialysis. Intensifying renal replacement regimens is effective in these patients.1, 6, 9, 10 Only a few cases of CKD associated pleural effusion have been reported in patients during the predialysis stage, even among those in whom the effusion is expected to resolve after the initiation of dialysis. We describe exudative pleural effusion in a CKD patient not receiving dialysis. The patient was refractory to conventional treatment such as continuous renal replacement therapy but improved completely with corticosteroid therapy.

Introduction Anthocyanins are potent antioxidant agents that protect against many degenerative diseases; however, they are unstable because they are vulnerable to external stimuli including temperature, pH and light. This vulnerability hinders the quality control of anthocyanin-containing berries using classical high-performance liquid chromatography (HPLC) analytical methodologies based on UV or MS chromatograms. Objective To develop an alternative approach for the quality assessment and discrimination of anthocyanin-containing berries, we used MS spectral data acquired in a short analytical time rather than UV or MS chromatograms. Method Mixtures of anthocyanins were separated from other components in a short gradient time (5 min) due to their higher polarity, and the representative MS spectrum was acquired from the MS chromatogram corresponding to the mixture of anthocyanins. Results The chemometric data from the representative MS spectra contained reliable information for the identification and relative quantification of anthocyanins in berries with good precision and accuracy. Conclusion This fast and simple methodology, which consists of a simple sample preparation method and short gradient analysis, could be applied to reliably discriminate the species and geographical origins of different anthocyanin-containing berries. These features make the technique useful for the food industry. Copyright © 2017 John Wiley & Sons, Ltd.

A series of binary PtRu catalysts with different Pt:Ru atomic ratios in a range from 7:3 to 3:7 are synthesized on carbon support using the colloidal method; they are then used for electrooxidation of glycerol in acidic media. X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray absorption spectroscopy analyses are used to investigate the particle size, size distribution, and structural and electronic properties of the prepared catalysts. The addition of Ru content to the Pt-based catalysts caused structural and electronic modifications over the PtRu alloy catalyst formation. The electrocatalytic activities of PtRu/C series catalysts are investigated by using the cyclic voltammetry technique. Among the prepared catalysts, the Pt5Ru5/C catalyst shows enhanced catalytic activity at least 40% higher than that of the Pt/C catalyst, with improved stability for glycerol electrooxidation; these improvements can be attributed to the structural and electronic modifications of the Pt catalysts. Using an electrocatalytic batch reactor, product analysis after the oxidation reaction is performed by high-performance liquid chromatography to determine and compare the reaction pathways on the Pt/C and PtRu/C catalysts. To understand different catalytic activities of glycerol oxidation on the PtRu alloy surfaces, density functional theory (DFT) calculations have been performed and discussed with the experimental results.

In the present work, a two-stage anaerobic digestion system (TSADS) was newly designed to produce biogas with a greatly reduced H2S content. The role of first (sulfidogenic)-stage digester was not only acidogenesis but also sulfidogenesis (sulfate reduction to H2S), which would minimize the input of H2S-producing source in the followed second (methanogenic)-stage digester. For the coexistence of acidogens and sulfate reducing bacteria (SRB) in the sulfidogenic-stage digester, it was found that pH played a crucial role. The acidogenic activity was not affected within a pH range of 4.5-6.0, while it was important to maintain a pH at 5.5 to achieve a sulfate removal efficiency over 70%. The highest sulfate removal attained was 78% at a hydraulic retention time (HRT) of 5 h at pH 5.5 ± 0.1. The H2S content in the biogas produced in the conventional single-stage digester (SSAD), used as a control, reached 1,650 ± 25 ppmv. In contrast, the biogas produced in the methanogenic-stage digester of the developed process had an H2S content of 200 ± 15 ppmv. Microbial analysis, done by the next generation sequencing technique, clearly showed the changes in community under different operating conditions. Desulfovibrio bastinii (4.9%) played a key role in sulfate removal in the sulfidogenic-stage of the TSADS owing to its characteristics of a short doubling time and growth in an acidic environment. This article is protected by copyright. All rights reserved

This study describes novel and simple conditions for the fabrication of collagen microfibers with specific physical and mechanical properties, which can then be potentially applied as cell-based matrices. The microfibers are fabricated from collagen hydrogels, using various concentrations of ethanol, in ethanol–water solvents. At higher ethanol concentration, fibers exhibited increased uniformity of surface morphology, decreased diameter, and increased tensile strength. The morphology of cells on microfibers varies due to the surface morphology of microfibers but the microfibers fabricated under all conditions investigated show similar number of attached cells on the surface of fibers, and cells sustain their viability for 90 h.

Objectives To evaluate the clinical efficacy of initial combined treatment of alpha-blocker plus dose-dependent anticholinergic agent compared to the alpha-blocker monotherapy in benign prostatic hyperplasia patients with overactive bladder. Methods Male lower urinary tract symptoms (LUTS) patients with International Prostate Symptom Score (IPSS) of 8 or higher, total overactive bladder Symptom Score (OABSS) of 3 or higher, and 2 points or higher in the OABSS questionnaire number 2 were enrolled. Eligible subjects (total n = 146) were randomly assigned to receive tamsulosin 0.2 mg (Group I, n = 44), tamsulosin 0.2 mg plus solifenacin 5 mg (Group II, n = 55), or tamsulosin 0.2 mg plus solifenacin 10 mg (Group III, n = 47) for 12 weeks. Efficacy and safety assessments for each group were done using detailed questionnaires, and evaluating urinary parameters such as maximal urinary flow rate (Qmax) and postvoid residual volume (PVR) at 4 and 12 weeks. Results Groups II and III (combined use of tamsulosin and solifenacin) showed significant improvement in storage symptoms compared to group I (tamsulosin monotherapy), as reflected by IPSS storage subscore and OABSS (P

The objective of our study was to investigate sexual reproduction of Daphnia magna associated with mating behaviors and hatching rates, according to different algal food sources. Since a diatom is known to contain more abundant long‐chain poly unsaturated fatty acids (PUFAs), we hypothesized that the diatom‐consuming D. magna would exhibit more successful reproduction rates. Upon the hypothesis, we designed three experiments using two algal species, a green alga (Chlorella vulgaris) and a diatom (Stephanodiscus hantzschii). From the results, we found that the mating frequency and copulation duration increased in the treatment with S. hantzschii, resulting in a significant increase of hatching rates of resting eggs. In the other two repetitive mating strategies (e.g., one female vs. multiple males, and one male vs. multiple females), we found that the hatching rates of resting eggs were greater in the S. hantzschii treatment. In addition to the mating strategy, male body size significantly increased in the diatom treatment, hence average diameter of penis was also statistically different among the treatments (greater diameter in the S. hantzschii treatment). To examine the effect of algal food quality, we estimated quantity of fatty acids in the two algal species. Our result showed that S. hantzschii had a higher proportion of long‐chain PUFAs than C. vulgaris. Furthermore, a stable isotope analysis revealed that carbon and nitrogen originated from S. hantzschii were more assimilated to D. magna. In summary, our study manifested that diatom consumption of D. magna leads to more successful sexual reproduction. We then discussed how the diatom consumption of zooplankton influences food web dynamics in a freshwater ecosystem.

Introduction High sodium intake is the main cause of fluid overload in hemodialysis (HD) patients, leading to increased cardiovascular mortality. High sodium intake is known to be associated with low salt taste acuity and/or high preference. As the zinc status could influence taste acuity, we analyzed the effect of zinc deficiency on salt taste acuity, preference, and dietary sodium intake in HD patients. Methods A total of 77 HD patients was enrolled in this cross-sectional study. Zinc deficiency was defined as serum zinc level with below 70 µg/mL. The patients were divided into two groups based on serum zinc level. Salt taste acuity and preference were determined by a sensory test using varying concentrations of NaCl solution, and dietary sodium intake was estimated using 3-day dietary recall surveys. Findings The mean salt recognition threshold and salt taste preference were significantly higher in the zinc deficient group than in the non-zinc deficient group. And there was significant positive correlation between salt taste preference and dietary sodium intake in zinc deficient group (r = 0.43, P = 0.002). Although, the dietary sodium intake showed a high tendency with no significance (P = 0.052), interdialytic weight gain was significantly higher in the zinc deficient group than in the non-zinc deficient group (2.68 ± 1.02 kg vs. 3.18 ± 1.02 kg; P = 0.047). Discussion Zinc deficiency may be related to low salt taste acuity and high salt preference, leading to high dietary sodium intake in HD patients.

Background The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site. Methods We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naive rats. Results Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0–3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3–6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naive rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αβmeATP. Conclusion Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain.

Biosensors based on a field-effect transistor platform allow continuous monitoring of biologically active species with high sensitivity due to the amplification capability of detected signals. To date, a large number of sensors for biogenic substances have used high-cost enzyme immobilization methods. Here, highly sensitive organic field-effect transistor (OFET)-based sensors functionalized with synthetic receptors are reported that can selectively detect acetylcholine (ACh+), a critical ion related to the delivery of neural stimulation. A cucurbit[6]uril (CB[6]) derivative, perallyloxyCB[6] ((allyloxy)12CB[6], AOCB[6]), which is soluble in methanol but insoluble in water, has been solution-deposited as a selective sensing layer onto a water-stable p-channel semiconductor, 5,5′-bis-(7-dodecyl-9H-fluoren-2-yl)-2,2′-bithiophene layer. The OFET-based sensors exhibit a detection limit down to 1 × 10–12 m of ACh+, which is six orders of magnitude lower than that of ion-selective electrode-based sensors. Moreover, these OFET-based sensors show highly selective discrimination of ACh+ over choline (Ch+). The findings demonstrate a viable method for the fabrication of OFET-based biosensors with high sensitivity and selectivity, and allow for practical applications of OFETs as high-performance sensors for biogenic substances.

This work was financially supported by grants from the National Research Council of Science and Technology (NST) by the Korean government (MSIP) (CRC-15-04-KIST, G15120, G16230, K16850 and K17850).

Occult hepatitis B virus (HBV) infection is defined as the presence of HBV DNA in the liver tissue and/or serum of subjects seronegative for hepatitis B surface antigen (HBsAg). Occult HBV infection of hemodialysis (HD) patients is informative in terms of virus transmission, reactivation after kidney transplantation, and the progression of liver disease. However, there is little detailed information about occult HBV infection in the context of virus endemicity. We tried to investigate the seroprevalence and clinical features of occult HBV infection in HD patients in HBV-endemic regions. We enrolled a total of 159 HD patients and 121 apparently healthy subjects at Dankook University Hospital and Jeju National University Hospital in Korea. HBsAg, anti-HBs, anti-HBc, and anti-hepatitis C virus (HCV) antibody levels were measured by radioimmunoassay. Serum levels of HBV DNA were measured by real-time polymerase chain reaction. The seroprevalence of occult HBV infection was 1.3% in HD patients and 2.5% in the healthy controls. This difference was not significant. The HBV load in all subjects with occult infection was

Background There is both clinical and experimental evidence to support the application of corticosterone in the management of inflammation and pain. Corticosterone has been used to treat painful inflammatory diseases and can produce antinociceptive effects. Epinephrine is synthesized from norepinephrine by the enzyme phenylethanolamine N-methyltransferase (PNMT) and works as an endogenous adrenoceptor ligand secreted peripherally by the adrenal medulla. It is currently unclear whether corticosterone's antinociceptive effect is associated with the modulation of peripheral epinephrine. Methods We first determined whether exogenous corticosterone treatment actually produced an antinociceptive effect in a formalin-induced pain model, and then examined whether this corticosterone-induced antinociceptive effect was altered by suppression of adrenal-derived epinephrine, using the following three suppression methods: (1) inhibition of the PNMT enzyme; (2) blocking peripheral epinephrine receptors; and (3) adrenalectomy. Results Exogenous treatment with corticosterone at a high dose (50 mg/kg), but not at lower doses (5, 25 mg/kg), significantly reduced pain responses in the late phase. Moreover, injection of 2,3-dichloro-a-methylbenzylamine, a PNMT enzyme inhibitor, (10 mg/kg) before corticosterone treatment caused a leftward shift in the dose-response curve for corticosterone and injection of propranolol (5 mg/kg), but not phentolamine, also shifted the dose-response curve to the left during the late phase. Chemical sympathectomy with 6-hydroxydopamine had no effect on corticosterone-induced antinociceptive effect, but injection of a low dose of corticosterone produced an antinociceptive effect in adrenalectomized animals. Conclusions These results demonstrate that suppression of epinephrine, derived from adrenal gland, enhances the antinociceptive effect of exogenous corticosterone treatment in an inflammatory pain model.

Summary Objective Persistent elevation of urinary albumin excretion (UAE), even within normal range, is an independent predictor for cardiovascular disease. Accumulating research suggests that low levels of vitamin D and high levels of parathyroid hormone (PTH) also increase cardiovascular disease risk. This study is intended to investigate the relationship between PTH, vitamin D levels and UAE. Methods We examined 2897 adults aged 50 and above, participating in the second year of the fifth Korea National Health and Nutrition Examination Survey (KNHANES V-2). Anthropometric and laboratory measurements were performed. Elevated UAE was defined as spot urinary albumin creatinine ratio equal or above 10. Results The proportion of elevated UAE (218%, 232%, 232%, 318%; P for trend = 0002) rose with increasing quartiles of PTH. The odds ratio for elevated UAE in the highest quartile of PTH was 72% higher than the lowest quartile group. There was no relationship between vitamin D and elevated UAE. Conclusions Elevated PTH levels are associated with elevated UAE in Korean adults aged 50 and above. Additional studies are needed to clarify this relationship.

Six phlorotannins, isolated from Eisenia bicyclis, were evaluated for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The minimum inhibitory concentrations (MIC) of the compounds were in the range 32 to 64 µg/mL. Phlorofucofuroeckol-A (PFF) exhibited the highest anti-MRSA activity, with an MIC of 32 µg/mL. An investigation of the interaction between these compounds and the β-lactam antibiotics ampicillin, penicillin, and oxacillin revealed synergistic action against MRSA in combination with compound PFF. To our knowledge, this is the first report on the anti-MRSA activity of phlorotannins from E. bicyclis. The results obtained in this study suggest that the compounds derived from E. bicyclis can be a good source of natural antibacterial agents against MRSA. Copyright © 2012 John Wiley & Sons, Ltd.

Nicotinic acetylcholine receptors (nAChRs) containing α6 and/or α4 subunits modulate the release of dopamine. However, few compounds can effectively discriminate between ligand-binding sites that contain α6 vs. α4 nAChR subunits. Using a chimeric (α6/α4) subunit, we showed that α-conotoxin BuIA binds the extracellular rat α6β2 vs. α4β2 interface with ∼60,000-fold selectivity. Chimeras containing residues from the α6 subunit were inserted into the homologous position of the α4 subunit to identify critical sequence segments. The region between residues 184 and 207 in the α6 subunit accounted for the potency difference. Chimeras within this region followed by point mutations were constructed for further definition. α6 Lys185, Thr187, and Ile188 form a triad of key residues that influence BuIA binding; when these 3 α6 residues were inserted into the α4 subunit, there was an ∼2000-fold increase in toxin potency. We used a crystal structure of BuIA bound to the acetylcholine-binding protein together with the structure of the Torepedo marmorata nAChR to build a homology model of BuIA bound to the interface between α6 and β2 subunits. The results indicate that the triad of α6 residues lies outside the C loop and is distantly located from bound BuIA (>10 Å). This suggests that alterations in potency are not caused by the direct interaction between the triad and BuIA. Instead, alterations in C-loop 3-dimensional structure and/or flexibility may account for differential potency. Thr198 and Tyr205 also contributed to BuIA potency. In addition, Thr198 caused BuIA potency differences between the closely related α6 and α3 subunits. Together, the findings provide insight into differences between the α6 and other α subunits that may be exploited by α-conotoxins to achieve binding selectivity.—Kim, H.-W., McIntosh, J. M. α6 nAChR subunit residues that confer α-conotoxin BuIA selectivity.

In this study, we investigated what environmental factors mainly influence the pattern of zooplankton communities in the regulated Nakdong River. Fifteen years of data (N = 629, 1994 to 2008) were used to analyze the patterns by means of self-organizing map (SOM), that is capable of extracting information through competitive and adaptive properties. A total of 34 variables (18 groups of zooplankton and 16 physicochemical parameters) were patterned onto the SOM, and then each variable was compared in accordance with three different annual rainfall patterns (i.e., dry, moderate, and wet). Finally, seven clusters were categorized according to Euclidian distance between the clusters on the SOM. Clear seasonal features for the variables were interpreted in five major categories, and two more subcategories were partitioned by a specific feature of zooplankton abundance and appearance. In the result, the patterns of zooplankton assemblage were mainly distinguished by water temperature, Secchi transparency, and river flow rate. In particular, the SOM result depicted a clear pattern of zooplankton assemblage clusters partitioned by annual precipitation, which accentuated the prolonged effect of dam regulation on plankton assemblage in a regulated river system.

OBJECTIVE To evaluate, in a well-controlled study, the effect of surgically induced partial bladder outlet obstruction (PBOO) on male erectile function in a rat model. MATERIALS AND METHODS PBOO was created in 17 adult male Sprague-Dawley rats by partial ligation of the proximal urethra. Sham-operated and PBOO rats were evaluated for urodynamic and erectile function at 4–8 weeks after surgery. Erectile responses to electrical field stimulation (EFS) to the major pelvic ganglion, and to erectogenic agents (1,1-diethyl-2-hydroxy-2-nitroso-hydrazine, DEA-NO, and Y-27632) were evaluated and the area under the curve (AUC, a product of the intracavernous pressure and duration) was used to denote the erectile response. RESULTS Experimental PBOO in rats significantly increased the mean (sem) bladder weight, to 256 (25) mg in PBOO rats vs 123 (24) mg in sham controls, and the voiding frequency to 1.01 (0.1) voids/min vs 0.72 (0.14) voids/min in sham controls (P 0.05); or to the erectogenic agents, the AUC for DEA-NO being 9000 (975) in PBOO rats vs 13 201 (2756) in sham controls, and the AUC for Y-27 632 being 44 915 (2462) and 45 907 (7408), respectively (P > 0.05). There was greater immunoreactivity to RhoA in bladder and penile tissues of PBOO than control rats. CONCLUSION PBOO does not affect erectile function in rats. Additional mechanisms or pathways might be involved in lower urinary tract symptom-related erectile dysfunction in humans.

Sigma sites, originally proposed as opioid receptor subtypes, are currently thought to represent unique receptors with a specific pattern of drug selectivity, a well-established anatomical distribution and broad range of functional roles including potential involvement in nociceptive mechanisms. We have recently demonstrated that intrathecal (i.t.) treatment with a sigma-1 receptor antagonist reduced formalin-induced pain behavior. In the present study, we investigated the potential role of spinal sigma-1 receptor agonists in peripherally initiated nociception and attempted to elucidate intracellular signaling mechanisms associated with spinal cord sigma-1 receptor activation in mice. The i.t. injection of the sigma-1 receptor agonists PRE-084 (PRE) or carbetapentane (CAR) significantly decreased tail-flick latency (TFL) and increased the frequency of paw withdrawal responses to mechanical stimulation (von Frey filament, 0.6 g) as well as the amount of Fos expression in the spinal cord dorsal horn induced by noxious paw-pinch stimulation. These PRE- or CAR-induced facilitatory effects on nociception were significantly blocked by i.t. pretreatment with the sigma-1 receptor antagonist, BD-1047, the phospholipase C (PLC) inhibitor, U-73,122, the Ca(2+)-ATPase inhibitor, thapsigargin, and the protein kinase C (PKC) inhibitor, chelerythrine. Western blot analysis further revealed that i.t. PRE or CAR injection significantly increased pan-PKC as well as the PKCalpha, epsilon, and zeta isoforms in the dorsal horn. Collectively, these findings demonstrate that calcium-dependent second messenger cascades including PKC are involved in the facilitation of nociception associated with spinal sigma-1 receptor activation.

Phosphorylation of the N-methyl-D-aspartate (NMDA) receptor NR1 subunit (pNR1) in the spinal cord is associated with increased neuronal responsiveness, which underlies the process of central sensitization. Because of the importance of NR1 in central sensitization, the first goal of this study was to examine both time- and lamina-dependent changes in spinal NR1 and pNR1 expression in a chronic constriction injury (CCI) model of neuropathic pain. Increased excitability of capsaicin sensitive primary afferents (CSPAs), which express TRPV1 receptors, also contributes to central sensitization. Thus, we next examined whether the depletion of CSPAs with resiniferatoxin (RTX) modified the change of spinal NR1 and pNR1 expression induced by CCI. Experimental rats were euthanized at 1, 3, 7, 14, and 28 days post-CCI surgery and spinal cords processed for NR1 or pNR1 immunostaining. The number of NR1 or pNR1-immunoreactive neurons was significantly increased in all lamina (I-VI) of the ipsilateral L4/L5 dorsal horn from 1 or 7 days post-CCI, respectively. Pretreatment with RTX (0.3mg/kg, s.c. in the scruff of the neck or intraplantar) 2 days prior to CCI completely prevented induction of thermal hyperalgesia, but not mechanical allodynia in neuropathic rats. Interestingly, RTX treatment significantly attenuated the CCI-induced upregulation of NR1 and pNR1 in spinal laminae I-II and V-VI, but not laminae III-IV as compared with that of vehicle-treated CCI rats. These findings demonstrate that the increased expression of NR1 and pNR1 in spinal laminae I-II and V-VI is dependent on activation of CSPAs, which ultimately contribute to the development of thermal hyperalgesia in neuropathic rats.

Background and purpose: Previously we demonstrated that the spinal sigma-1 receptor (Sig-1 R) plays an important role in pain transmission, although the exact mechanism is still unclear. It has been suggested that Sig-1 R agonists increase glutamate-induced calcium influx through N-methyl-D-aspartate (NMDA) receptors. Despite data suggesting a link between Sig-1 Rs and NMDA receptors, there are no studies addressing whether Sig-1 R activation directly affects NMDA receptor sensitivity.