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We present a case of digoxin toxicity in the context of dehydration, renal dysfunction and concomitant use of the macrolide antibiotic, clarithromycin, which is known to inhibit P-glycoprotein-mediated efflux mechanisms of digoxin. A focused review of the literature is presented. Health care providers need to be vigilant of this mechanism of drug-drug interaction, which is also relevant to other commonly used cardiovascular drugs.

Rheumatoid arthritis (RA) is one of the major autoimmune diseases of global prevalence. The use of the anti-inflammatory drugs for the treatment of RA is associated with severe adverse reactions and toxicity. This limitation has necessitated the search for novel therapeutic products. We report here a traditional Chinese medicine-based herbal formula, Huo luo xiao ling dan (HLXL), which has potent antiarthritic activity as validated in the rat adjuvant-induced arthritis (AA) model. HLXL (2.3 g/Kg) was fed to Lewis (RT.11) rats daily by gavage beginning at the onset of arthritis and then continued through the observation period. HLXL inhibited the severity of ongoing AA. This suppression of arthritis was associated with significant alterations in the T cell proliferative and cytokine responses as well as the antibody response against the disease-related antigen, mycobacterial heat-shock protein 65 (Bhsp65). There was a reduction in the level of the proinflammatory cytokines IL-17 and IL-1βbut enhancement of the anti-inflammatory cytokine IL-10 level. In addition, there was inhibition of both the anti-Bhsp65 antibody response and the serum level of nitric oxide. Thus, HLXL is a promising CAM modality for further testing in RA patients.

Salvinorin A is a naturally-occurring potent and selective kappa opioid receptor agonist, and smoking salvinorin A produces the most intense hallucinogenic effects in human. Eight neoclerodane diterpene derivatives were isolated from the smoke of salvinorin A, and their structures were identified by spectroscopic methods. The major structural changes include epimerizations, eliminations, and rearrangements.

Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective κ opioid receptor (KOPR) agonist. Based on the SAR, its C-2 position is one of the key binding sites and has very little space tolerance (3–4 carbons atoms) and limited to only lipophilic groups. In our attempt to prepare PET brain imaging agent for mapping KOPR, a series of C-2 halogenated analogs have been synthesized and screened for binding affinity at κ (KOPR), μ (MOPR), and δ (DOPR). These C-2 halogenated analogs with sequential changes of atomic radius and electron density serve as excellent molecular probes for further investigating the binding pocket at C-2, particularly on the effects of α verses β configuration at C-2 position. The results of KOPR binding and functional studies reveal β isomer in general binds better than α isomer with the exception of iodinated analogs and none of the C-2 halogenated analogs shows any improvement of KOPR binding affinity. Interestingly, functional assay has characterized that 6b is a partial agonist with Emax of 46% of the kappa receptor full agonist U50,488H at 250 nM (Ki). We have also observed that the affinity to the kappa receptor increases with atomic radius (I > Br > Cl > F) which is in good agreement with halogen bonding interactions reported in the literature.

Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and also displays antioxidant, anti-inflammatory, and immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated the hepatoprotective actions of the seven major flavonolignans and one flavonoid that comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-alpha-induced NF-kappaB transcription, virus-induced oxidative stress, and T-cell proliferation. All compounds were well tolerated by Huh7 human hepatoma cells up to 80 muM, except for isosilybin B, which was toxic to cells above 10 muM. Select compounds had stronger hepatoprotective functions than silymarin in all assays tested except in T cell proliferation. Pure compounds inhibited JFH-1 NS5B polymerase but only at concentrations above 300 muM. Silymarin suppressed TNF-alpha activation of NF-kappaB dependent transcription, which involved partial inhibition of IkappaB and RelA/p65 serine phosphorylation, and p50 and p65 nuclear translocation, without affecting binding of p50 and p65 to DNA. All compounds blocked JFH-1 virus-induced oxidative stress, including compounds that lacked antiviral activity. The most potent compounds across multiple assays were taxifolin, isosilybin A, silybin A, silybin B, and silibinin, a mixture of silybin A and silybin B. The data suggest that silymarin- and silymarin-derived compounds may influence HCV disease course in some patients. Studies where standardized silymarin is dosed to identify specific clinical endpoints are urgently needed.

Eleven authenticated botanicals used in the traditional Chinese medicine Huo-Luo-Xiao-Ling Dan were screened for ligands to cyclooxygenase (COX) using pulsed ultrafiltration liquid chromatography-mass spectrometry, and a mass spectrometry-based enzyme assay was used to determine the concentration of each of 17 ligands that inhibited COX-1 or COX-2 by 50% (IC(50)). Acetyl-11-keto-beta-boswellic acid, beta-boswellic acid, acetyl-alpha-boswellic acid, acetyl-beta-boswellic acid, and betulinic acid were COX-1 selective inhibitors with IC(50) values of approximately 10 microM. Senkyunolide O and cryptotanshinone were COX-2 selective inhibitors with IC(50) values of 5 microM and 22 microM, respectively. Roburic acid and phenethyl-trans-ferulate inhibited COX-1 and COX-2 equally. COX inhibition and the IC(50) values of most of these natural product ligands have not been reported previously.

In pinhole type integral imaging, the viewing angle and resolution are limited by pinhole interval. For enhancement of viewing angle and resolution, we propose the pinhole type integral imaging using color filters of LCD panel.

Improved optical depth converter by using a pair of curved lens array and convex mirror array is proposed. The proposed system is capable of orthoscopic/pseudoscopic image conversion with enhanced optical power efficiency.

The high rate of HIV-1 mutation and the frequent sexual transmission highlight the need for novel therapeutic modalities with broad activity against both CXCR4 (X4) and CCR5 (R5)-tropic viruses. We investigated a large number of natural products, and from Sargassum fusiforme we isolated and identified palmitic acid (PA) as a natural small bioactive molecule with activity against HIV-1 infection. Treatment with 100 microM PA inhibited both X4 and R5 independent infection in the T cell line up to 70%. Treatment with 22 microM PA inhibited X4 infection in primary peripheral blood lymphocytes (PBL) up to 95% and 100 microM PA inhibited R5 infection in primary macrophages by over 90%. Inhibition of infection was concentration dependent, and cell viability for all treatments tested remained above 80%, similar to treatment with 10(-6)M nucleoside analogue 2', 3'-dideoxycytidine (ddC). Micromolar PA concentrations also inhibited cell-to-cell fusion and specific virus-to-cell fusion up to 62%. PA treatment did not result in internalization of the cell surface CD4 receptor or lipid raft disruption, and it did not inhibit intracellular virus replication. PA directly inhibited gp120-CD4 complex formation in a dose-dependent manner. We used fluorescence spectroscopy to determine that PA binds to the CD4 receptor with K(d) approximately 1.5 +/- 0.2 microM, and we used one-dimensional saturation transfer difference NMR (STD-NMR) to determined that the PA binding epitope for CD4 consists of the hydrophobic methyl and methelene groups located away from the PA carboxyl terminal, which blocks efficient gp120-CD4 attachment. These findings introduce a novel class of antiviral compound that binds directly to the CD4 receptor, blocking HIV-1 entry and infection. Understanding the structure-affinity relationship (SAR) between PA and CD4 should lead to the development of PA analogs with greater potency against HIV-1 entry.

Innovations in semiconductor fabrication processes have driven process shrinks partly to fulfill the need for low power, system-on-chip (SOC) devices. As the process is innovated, it influences the related design debug and failure analysis which have gone through many changes. Historically for signal probing, engineers analyzed signals from metal layers by using e-beam probing methods [1]. But due to the increased number of metal layers and the introduction of flip chip packages, new signal probing systems were developed which used time resolved photon emission (TRE) to measure signals through the backside. However, as the fabrication process technology continues to shrink, the operating voltage drops as well. When the operating voltage drops below 1.0V, signal probing systems using TRE find it harder to detect the signals [2]. Fortunately, Laser Voltage Probing (LVP) technology [3] is capable of probing beyond this limitation of TRE. In this paper, we used an LVP system to analyze and identify a functional shmoo hole failure. We also proposed the design change to prevent its reoccurrence.

The Korea Superconducting Tokamak Advanced Research (KSTAR) device is an advanced superconducting tokamak to establish scientific and technological bases for an attractive fusion reactor. This device requires 3.5 Tesla of toroidal field (TF) for plasma confinement, and requires a strong poloidal flux swing to generate an inductive voltage to produce and sustain the tokamak plasma. KSTAR was originally designed to have 16 serially connected TF magnets for which the nominal current rating is 35.2 kA. KSTAR also has 7 pairs of poloidal field (PF) coils that are driven to 1 MA/sec for generation of the tokamak plasma according to the operation scenarios. The KSTAR Magnet Power Supply (MPS) was dedicated to the superconducting (SC) coil commissioning and 1st plasma experiment as a part of the system commissioning. This paper will describe key features of KSTAR MPS for the 1st plasma experiment, and will also report the engineering and commissioning results of the magnet power supplies.

A case of unusual reactions consisting of involuntary abnormal facial movements in a child following exposure to the 5-HT3 receptor antagonists for prophylaxis against chemotherapy-induced vomiting is presented. Potential mechanisms for these reactions are discussed.

To unambiguously confirm the actual product in autoxidation of salvinorin A under basic conditions, deacetyl-1,10-didehydrosalvinorin G was synthesized from salvinorin C via intermediate salvinorin H. Furthermore, oxidation of salvinorin D with manganese dioxide gave salvinorin G in good yield.

Study Design. Cross-sectional study. Objective. The purpose of this study was to examine disc morphology and spinal mobility in subjects with varying degrees of osteoporosis. Summary of Background Data. There was limited information on the effect of osteoporosis on lumbar morphology and spinal mobility. It was also unclear how osteoporosis affects the nonosseous tissues such as the intervertebral disc. Methods. Ninety elderly subjects with varying bone mineral densities (22 normal, 28 osteopenia, 40 osteoporosis) were recruited from an osteoporosis clinic. Lateral radiographs and magnetic resonance images of their lumbar spines were obtained. An electromagnetic tracking device was employed to measure the ranges of motion of the whole lumbar spine. Results. Although the thoracic spine had been shown to have decreased anterior vertebral body height in subjects with osteoporosis, this study revealed that the anterior height was increased in the lumbar region. Osteoporosis was associated with expansion of the middle of the disc with corresponding collapse of vertebral bodies, but osteoporosis was found not to be related to either disc preservation or degeneration. No significant change in spinal mobility was observed in patients with osteoporosis. Conclusion. Osteoporosis does not only affect the bone but also the nonosseous tissues. It was found to be associated with expansion of the intervertebral disc, which was likely to be secondary to changes in the vertebral endplate.

Correlation between kinematics and morphological characteristics of lumbar spine was studied in subjects with varying bone mineral density. Effect of morphological characteristics and bone mineral density on the lumbar spine movement was investigated. Morphology parameters were measured from radiographs and a high-frequency motion tracking device were employed to detect surface movement of lumbar spine. Multiple regression analysis identified factors influencing lumbar kinematics while ANOVA examined differences in morphology with normal bone mineral density, osteopenia and osteoporosis. The results show that morphological characteristics, such as wedging deformity, are indeed influential to the kinematics. Related to our previous report, abnormal lumbar kinematic pattern in the subjects with osteoporosis, this study shows although morphological characteristics were found significantly different among normal, osteopenia, and osteoporosis subjects, the change in lumbar kinematic pattern could not be fully explained by the altered vertebral or disc morphology.

Measurement errors of skin-mounted sensors in measuring forward bending movement of the lumbar spines are investigated. In this investigation, radiographic images capturing the entire lumbar spines' positions were acquired and used as a 'gold' standard. Seventeen young male volunteers (21 (SD 1) years old) agreed to participate in the study. Light-weight miniature sensors of the electromagnetic tracking systems-Fastrak were attached to the skin overlying the spinous processes of the lumbar spine. With the sensors attached, the subjects were requested to take lateral radiographs in two postures: neutral upright and full flexion. The ranges of motions of lumbar spine were calculated from two sets of digitized data: the bony markers of vertebral bodies and the sensors and compared. The differences between the two sets of results were then analyzed. The relative movement between sensor and vertebrae was decomposed into sensor sliding and titling, from which sliding error and titling error were introduced. Gross motion range of forward bending of lumbar spine measured from bony markers of vertebrae is 67.8 degrees (SD 10.6 degrees ) and that from sensors is 62.8 degrees (SD 12.8 degrees ). The error and absolute error for gross motion range were 5.0 degrees (SD 7.2 degrees ) and 7.7 degrees (SD 3.9 degrees ). The contributions of sensors placed on S1 and L1 to the absolute error were 3.9 degrees (SD 2.9 degrees ) and 4.4 degrees (SD 2.8 degrees ), respectively.

Publisher Summary The three mammalian natriuretic peptides (NPs), A-type natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), are genetically distinct but share structural similarities. Human ANP, BNP, and CNP are synthesized as preprohormones, which are subsequently split into prohormones by proteolytic cleavage of an N-terminal signal peptide. Human prepro-ANP is a 151-amino acid (AA) peptide that is cleaved to the 126-AA pro-ANP, whereas human prepro-BNP is a 134-AA peptide that is cleaved to the 108-AA pro-BNP. Pro-ANP and pro-BNP are stored in secretory granules in atrial cardiomyocytes and are cleaved to form ANP and BNP, respectively, upon secretion. The conversion of pro-ANP to ANP is mediated by corin, a transmembrane cardiac serine protease. Both human ANP, a 28-AA peptide, and human BNP, a 32-AA peptide, are released from the myocardium in response to various physiologic and pathophysiologic stimuli, such as myocardial wall stretch. Human pro-CNP consists of 103 AA residues and is processed by furin, an intracellular endoprotease, to the mature 53-AA CNP. CNP-53, which is found primarily in the brain, the heart, and endothelial cells, may be further cleaved to CNP-22.

Heavy-water-reactor (HWR) fuel manufacturing involves the fabrication of high density natural UO 2 pellets with controlled microstructure. It is necessary to investigate the correlation between powder characteristics, pellet properties and process parameters, especially when the UO 2 powders are from different conversion processes. To establish the UO 2 pelletizing technology better to obtain such tightly quality controlled pellets, it is found necessary, apart from the quality requirements described in various specifications, to determine the particle morphology, the pore size distribution in particular, with regard to the compaction behaviour, which strongly affects the densification during sintering. Pore structures of different UO 2 powders converted via the AUC and ADU processes and the evolution of pore size distribution in the compacted pellets from these different UO 2 powders are analysed and compared by mercury porosimetry and microstructure observations of compacted pellets by scanning electron microscopy. Further, the connection of the evolution of pores in compacted pellets to the attainable densities of sintered pellets is discussed for the optimization of process parameters and as a proposal for quality control requirements and methods.

Dual counter-current chromatoraphy is a newly developed separation method which allows the performance of classic counter-current distribution in a highly efficient manner. The principles of CCC and its capabilities, as illustrated by several applications in natural products isolations, are reviewed.

Background & Aims Silymarin, an extract from the seeds of the milk thistle plant Silybum marianum, has been used for centuries for the treatment of chronic liver diseases. Despite common use by patients with hepatitis C in the United States, its clinical efficacy remains uncertain. The goal of this study was to determine whether silymarin has in vitro effects on immune function that might have implications for its potential effect on hepatitis C virus (HCV)-induced liver disease. Methods Freshly isolated peripheral blood mononuclear cells (PBMC) and T cells from HCV-infected and uninfected subjects were tested in vitro for responses to nonspecific and antigenic stimulation in the presence and absence of a standardized preparation of silymarin (MK001). Results Minimal MK001 toxicity on PBMC was found at concentrations between 5 and 40 μg/mL. MK001 dose dependently inhibited the proliferation and secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 by PBMC stimulated with anti-CD3. In addition, MK001 inhibited proliferation by CD4+ T cells to HCV, Candida, and tetanus protein antigens and by HLA-A2/HCV 1406–1415-specific CD8+ T cells to allogeneic stimulation. MK001 inhibited T-cell TNF-α and IFN-γ cytokine secretion to tetanus and Candida protein antigens. Finally, MK001 inhibited nuclear factor-κB transcriptional activation after T-cell receptor-mediated stimulation of Jurkat T cells, consistent with its ability to inhibit Jurkat T-cell proliferation and secretion of IL-2. Conclusions Silymarin's ability to inhibit the proliferation and proinflammatory cytokine secretion of T cells, combined with its previously described antiviral effect, suggests a possible mechanism of action that could lead to clinical benefit during HCV infection.

Lumbar spine kinematics was studied in subjects with normal bone mineral density, osteopenia and osteoporosis to determine the effect of bone mineral density and morphology on the flexion-extension movement patterns of the lumbar spine. Lateral radiographs and skin-mounted electromagnetic motion tracking sensors were employed to study lumbar spine kinematics using a Bayesian Belief Network model. The predicted angular displacement of the vertebrae had a high correlation (r = 0.91, p0.001) with the actual movements. The overall mean error was -0.51 degrees +/- 3.11 degrees. Intervertebral angular displacement and velocity consistently increased from L1/L2 to L5/S1. Differences were observed in the movement pattern between normal subjects and those with decreased bone density. In normal subjects, vertebral angular acceleration consistently decreased from the upper to the lower vertebrae but the same consistent predictable pattern was not observed in the subjects with decreased bone mineral density. It is possible that these changes in kinematic behaviours are related to morphological changes as well as altered neuromuscular functions.

The aim of this study was to determine the suitability of inertial sensors for motion analysis research. Inertial sensors (Xsens Technologies, Netherlands) consisting of 3D gyroscopes, accelerometers and a magnetometer were compared against an electromagnetic motion tracking system (Fastrak, Polhemus, USA) for measuring motions of an artificial hinge joint and random 3D motions. Subsequently, to assess the feasibility of using inertial sensors for human motion analysis, the movements of the hip joint during walking were recorded in 20 normal asymptomatic subjects. The comparative study demonstrated good agreement between the inertial and electromagnetic systems. Measurements obtained for hip joint movement during walking (flexion, extension and step length) were similar to those reported in previous studies (flexion 38.8 degrees , extension 6.6 degrees , step frequency 1.02Hz). We conclude that the inertial sensors studied have the potential to be used for motion analysis and clinical research.

Background The present study aims to determine the time spent in different static trunk postures during a typical working day of workers in a special school for the severe handicaps. Methods Eighteen workers with low back pain (LBP) and fifteen asymptomatic workers were recruited. A cross-sectional design was employed to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T12 level of the back of the subjects. Results The results of ANCOVA revealed that subjects with LBP spent significantly longer percentage of time in static trunk posture when compared to normal (p < 0.05). It was also shown that they spent significantly longer time in trunk flexion for more than 10° (p < 0.0125). Conclusion An innovative method has been developed for continuous tracking of spinal posture, and this has potential for widespread applications in the workplace. The findings of the present investigation suggest that teachers in special schools are at increased risk of getting LBP. In order to minimise such risk, frequent postural change and awareness of work posture are recommended.

Lumbar spine kinematics were assessed and studied in subjects with normal bone mineral density, osteopenia, and osteoporosis to examine the extension-flexion movement pattern and determine the effect of bone mineral density on the movement pattern of lumbar spine. Both radiographs and surface motion tracking were employed to measure lumbar spine kinematics. Several movement patterns were consistently observed on all subjects, while subjects with osteopenia or osteoporosis do not possess the same ordered vertebral acceleration seen in subjects with normal bone density. This is the first study showing altered kinematic pattern during lumbar spine movement in subjects with osteoporosis. The results provide new insight in the pathology of osteoporotic patients, which would help clinical applications as well.

A fuel performance analysis code for a very high temperature gas-cooled reactor (VHTR) COPA (Co ated Pa rticle) is being developed at the Korea Atomic Energy Research Institute (KAERI). The COPA code consists of nine modules: BURN, TEMTR, TEMPEB, TEMBL, MECH, FAIL, FPREL, ABAQ, and MPRO. The BURN determines neutron flux and fluence at a location of a reactor core, and then calculates a fuel burnup, a fission rate per volume and a fission product inventory throughout a fuel particle and a fuel element. The TEMTR, TEMPEB and TEMBL calculate the temperature distributions in a coated fuel particle, a pebble and a fuel block by using a one-dimensional finite difference method, respectively. The MECH performs mechanical calculations on a coated fuel particle by using a finite element method. The FAIL performs probabilistic calculations to estimate the failure probabilities of the coating layers during an experiment or a reactor operation. The FPREL estimates the migrations of gaseous and metallic fission products through a fuel particle and a fuel element by using a one-dimensional finite difference method. The ABAQ performs the analysis of the crack and debonding in a coated fuel particle. The MPRO calculates the material properties of the kernel, low-density pyrocarbon, high-density pyrocarbon, silicon carbide, matrix graphite, and structural graphite. Each module is used to produce input data for other modules or is inserted into other modules. The COPA code is one of the computer codes taking part in the IAEA-CRP-6 benchmarking program. The stresses and failure fractions calculated by the COPA-MECH and COPA-FAIL showed good agreements with the results by the other countries’ codes. In order to establish a good database of the related material properties, KAERI is participating in an international irradiation experiment, is planning its own irradiation and post-irradiation experiments, and will perform ab-initio calculations on the fuel materials.Copyright © 2008 by ASME

Bioactivity-guided fractionation of Notopterygium forbesii has resulted in the isolation of one new coumarin glycoside and one new phenethyl vanillate, together with seventeen known compounds. The structures of these compounds were characterized by spectroscopic methods. These compounds were evaluated for their binding affinities to the opioid and dopamine receptors, and falcarindiol showed weak binding affinities to opioid receptors and moderate affinity for D1 receptor (K(i)=192+/-6 nM).

Salvinorin (Sal) A is a naturally occurring, selective kappa opioid receptor (KOPR) agonist with a short duration of action in vivo. Pharmacological properties of a C(2) derivative, 2-methoxymethyl (MOM)-Sal B, were characterized. MOM-Sal B bound to KOPR with high selectivity and displayed approximately 3-fold higher affinity than U50,488H [(trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide methanesulfonate] and Sal A. It acted as a full agonist at KOPR in guanosine 5'-O-(3-[(35)S]thio)triphosphate binding and was approximately 5- and approximately 7-fold more potent than U50,488H and Sal A, respectively. In Chinese hamster ovary cells stably expressing KOPR, all three kappa agonists internalized or down-regulated KOPR to similar extents, with MOM-Sal B being the most potent. In mice, MOM-Sal B (0.05-1 mg/kg s.c.) caused immediate and dose-dependent immobility lasting approximately 3 h, which was blocked by norbinaltorphimine. In contrast, ambulation in a Y-maze was increased when rats received MOM-Sal B (1-5 mg/kg s.c.). In addition, MOM-Sal B (0.5-5 mg/kg i.p.) produced antinociception (hot-plate test) and hypothermia in a dose-dependent manner in rats. MOM-Sal B was more potent than U50,488H in both tests and more efficacious than U50,488H in the hot-plate test. These latter two in vivo effects were blocked by norbinaltorphimine, indicating KOPR-mediated actions. Sal A at 10 mg/kg elicited neither antinociception nor hypothermia 30 min after administration to rats. In summary, MOM-Sal B is a potent and efficacious KOPR agonist with longer lasting in vivo effects than Sal A.

Electroacupuncture (EA) has been shown to modify the effects of various drugs of abuse, including alcohol. Inbred P rats were trained to drink alcohol voluntarily and then subjected to two periods of alcohol deprivation lasting 3 days. During the second deprivation, the rats received either EA or sham EA. The rats were pretreated with naltrexone (5 mg/kg) or saline 30 min before each of the EA or sham EA sessions. Approximately 6 h after the last naltrexone or saline treatment, the alcohol tubes were returned and alcohol and water intakes were recorded later at 2, 4, 6, and 24 h. Only EA led to a decrease in alcohol intake, which was most prominent at 6 and 24 h, and this inhibitory effect of EA was blocked by naltrexone, suggesting that activation of the endogenous opiate system may be responsible for EA’s effects on alcohol intake in the alcohol-dependent iP rats.

Chronic morphine administration induces functional and morphological alterations in the mesolimbic dopamine system (MLDS), which is believed to be the neurobiological substrate of opiate addiction. Our previous studies have demonstrated that peripheral electrical stimulation (PES) can suppress morphine withdrawal syndrome and morphine-induced conditioned place preference (CPP) in rats. The present study was designed to investigate if PES could reverse the cell size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the MLDS. Immunohistochemical observations showed that the cell size of dopaminergic neurons in the VTA reduced significantly in the chronic morphine treated rats with a concomitant decrease in the number of BDNF-positive cells compared to saline-treated rats. A much milder morphological change, accompanying with an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated 100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant up-regulation of BDNF protein level in the VTA in the rats received 100 Hz PES after morphine abstinence. These results demonstrate for the first time that the PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulated the BDNF protein level in the VTA. Activation of endogenous BDNF by PES may play a role in the recovery of the injured dopaminergic neurons, thus underlying the effectiveness of PES in the treatment of morphine addiction.

A spayed female Shetland sheep dog aged 12 years was presented for examination with ataxia and hindlimb paralysis. Extradural spinal cord compression was found at the level of vertebrae C6-C7 by radiography and myelocomputed tomography. A jelly-like mass (0.6 x 1.3 cm) was removed surgically. Histopathological findings were characterized by proliferation of vacuolated polygonal cells (physaliphorous cells) in a mucinous matrix and the presence of chondroid tissue shown immunohistochemically to express S-100. The physaliphorous cells were immunolabelled strongly for vimentin and S-100, and weakly for cytokeratin. A diagnosis of canine cervical chondroid chordoma was made. This is considered to be the first report of a chondroid chordoma originating from the cervical region of the spine in the dog.

Free electron laser (FEL) is the most powerful source in the THz range. The main task is to decrease its size and cost to a laboratory scale. An inexpensive and compact THz FEL has been developed at KAERI (Y.U. Jeong et al., 2001), (Y.U. Jeong et al., 2005) and it is expected to play an important role in encouraging advanced THz applications for biomedical imaging due to its higher power and spectral brightness when compared to the table-top sources.

Since the discovery of atrial natriuretic factor by de Bold et al., there has been tremendous progress in our understanding of the physiologic, diagnostic and therapeutic roles of the natriuretic peptides (NPs) in health and disease. Natriuretic peptides are endogenous hormones that are released by the heart in response to myocardial stretch and overload. Three mammalian NPs have been identified and characterized, including atrial natriuretic peptide (ANP or atrial natriuretic factor), B-type natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). In addition, Dendroaspis natriuretic peptide (DNP) has been isolated from the venom of Dendroaspis angusticeps (the green mamba snake), and urodilatin from human urine. These peptides are structurally similar and they consist of a 17-amino-acid core ring and a cysteine bridge. Both ANP and BNP bind to natriuretic peptide receptor A (NPR-A) that are expressed in the heart and other organs. Activation of NPR-A generates an increase in cyclic guanosine monophosphate, which mediates natriuresis, inhibition of renin and aldosterone, as well as vasorelaxant, anti-fibrotic, anti-hypertrophic, and lusitropic effects. The NP system thus serves as an important compensatory mechanism against neurohumoral activation in heart failure. This provides a strong rationale for the use of exogenous NPs in the management of acutely decompensated heart failure. In this article, the therapeutic applications of NPs in the acute heart failure syndromes are reviewed. Emerging therapeutic agents and areas for future research are discussed.

The surface method of measuring the movements of lower thoracic and lumbar spine with osteoporosis using Fastrak#174; was examined for validity. There is an increasing awareness of the health risks of exposure to radiation associated with repeated radiographic assessment of spinal curvature and spinal movements. As a skin-surface measurement device, Fastrak#174; was employed to study the effect of low bone mineral density on spine motion. However, the reliability and validity of data recorded has not been established. The purpose of this study was to develop a methodology to determine the accuracy of the surface measurement device when it is applied to the motion analysis of osteoporotic spine. The results obtained indicated that the rotation angle of lumbar and lower thoracic spine could be predicted with acceptable accuracy from the data collected from skin-mounted sensors, while the prediction error of translational movements were not acceptable.

Chinese herbal medicine has been used for thousands of years in China and other Asian countries to treat a variety of inflammatory diseases. The classic Chinese herbal formula, Huo Luo Xiao Ling Dan (活络效灵丹, HLXL) is commonly used in traditional Chinese herbal medicine for the treatment of joint pain and other symptoms of arthritis. The present study is an investigation of the effects of a modified HLXL extract on persistent hyperalgesia and edema in rats with peripheral inflammation. Inflammation was induced by injecting complete Freund's adjuvant (CFA) into one hind paw. Four dosages of the extract were compared to a vehicle control. Each was administered intragastrally (i.g.) daily for seven days beginning one day before CFA. Hyperalgesia was assessed using a paw withdrawal latency (PWL) test and edema was determined by measuring paw thickness at pre-CFA and 2 hours, 24 hours, and 5 days post-CFA. Immunohistochemistry was performed 2 hours post-CFA to determine spinal Fos protein expression. Adverse effects of the extract were monitored by observing the animals closely for unusual behavioral changes. Compared to the control, HLXL at the two lower dosages (0.575 g/kg and 1.15 g/kg) were effective in the later stage (day 5) of inflammatory hyperalgesia and edema, while the two higher dosages (2.3 g/kg and 4.6 g/kg) alleviated early stage hind paw inflammation and hyperalgesia and facilitated recovery from paw edema and hyperalgesia during the late stage. HLXL at 2.30 g/kg significantly suppressed Fos expression in laminae I–II, III–IV and V–VI ipsilaterally and in III-IV contralaterally. No significant signs of toxicity or adverse effects were observed. The data suggest that HLXL dosage-dependently attenuates CFA-induced inflammation and hyperalgesia, at least in part by inhibiting noxious transmission at the dorsal horn of the spinal cord.

Aryl C-glycosides are stable analogs of the corresponding O-glycosides. Because of their favorable pharmacological profiles attributed primarily to the C-glycosyl moiety, aryl C-glycosides have gained increasing popularity as drug candidates. In this review we focus on the synthesis of aryl C-glycosides including puerarin and kendomycin. This review is organized based on the type of chemistry used in the assembly of the C-glycosides with the following sub-sections: electrophilic reaction, cross-coupling reaction, free radical reaction, cyclization, intramolecular O-C rearrangement, umpolung, and miscellaneous reactions.

This study was undertaken to assess the pharmacokinetic profile of puerarin, the major isoflavone found in a kudzu (Pueraria lobata) extract after acute and repeated administration.Participants were given either single or repeated doses of kudzu extract, and blood samples were collected for either 8 or 72 hours for subsequent pharmacokinetic analyses of puerarin.Using WinNonlin pharmacokinetic data analysis software, puerarin was found to be rapidly absorbed via the oral route, reach peak levels at 2 hours, and have a half-life of approximately 4.3 hours. The elimination half-life was not significantly altered after repeated administration.A formulation of kudzu extract delivers a large amount of the principal isoflavone in a rapid manner. The elimination rate constants and the mono-exponential decline in blood levels suggest that a one compartment model adequately explains how puerarin is handled by the body. Three times a day dosing is recommended as accumulation will not occur, and plasma levels remain at levels that are biologically active, even 8 hours after the last steady-state dose.

The amyloid precursor protein (APP) is cleaved enzymatically by nonamyloidogenic and amyloidogenic pathways. alpha-Secretase (alpha-secretase), cleaves APP within the beta-amyloid (Abeta) sequence, resulting in the release of a secreted fragment of APP (alphaAPPs) and precluding Abeta generation. In this study, we investigated the effects of an acetylcholinesterase inhibitor, huperzine A (Hup A), on APP processing and Abeta generation in human embryonic kidney 293 cells transfected with human APP bearing the Swedish mutation (HEK293 APPsw). Hup A dose dependently (0-10 microM) increased alphaAPPs release and membrane-coupled APP CTF-C83, suggesting increased APP metabolism toward the nonamyloidogenic alpha-secretase pathway. The metalloprotease inhibitor TAPI-2 inhibited the Hup A-induced increase in alphaAPPs release, further suggesting a modulatory effect of Hup A on alpha-secretase activity. The synthesis of full-length APP and cell viability were unchanged after Hup A incubation, whereas the level of Abeta(Total) was significantly decreased, suggesting an inhibitory effect of Hup A on Abeta production. Hup A-induced alphaAPPs release was significantly reduced by the protein kinase C (PKC) inhibitors GF109203X and Calphostin C. These data, together with the finding that the PKCalpha level was enhanced prior to the increase of alphaAPPs secretion, indicate that PKC may be involved in Hup A-induced alphaAPPs secretion by HEK293 APPsw cells. Our data suggest alternative pharmacological mechanisms of Hup A relevant to the treatment of Alzheimer's disease.

Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent and highly selective agonist for the κ opioid receptor. For exploration of its structure and activity relationships, further modifications, such as reduction at the C(4) position, have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human κ-opioid receptor and several new full agonists have been identified.

The current real-time PCR (polymerase chain reaction) platforms, which can detect and quantify several target DNA simultaneously, are equipped with discrete optics and detectors for different fluorescence wavelengths. However, the optical loss, due to the different lengths of the channels for several dyes, lowers the performance of fluorescence detection. Especially on the PCR platforms of lab-on-a-chip system, for the dispersion of the fluorescence in the micro fluidic channels, the received fluorescence is much lower than the emitted. To enhance the received intensity on the detection system is therefore a critical issue. The proposed fluorescence detection system, composing of an ultra-sensitive spectrometer, can provide continuous wavelength detection and can be employed for multiple DNA quantification and genotyping in a single reaction. For the tests to the genotyping ability, the melting temperatures of B type HBV and C type HBV can be distinguished by the difference of 1.1degC.The test results in this research show the same degree of sensitivity for DNA quantification and reproducibility within five intra assay samples as compared with a commercial one