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Electrocyclic reactions are characterized by the concerted formation and cleavage of both {\sigma} and {\pi} bonds through a cyclic structure. This structure is known as a pericyclic transition state for thermal reactions and a pericyclic minimum in the excited state for photochemical reactions. However, the structure of the pericyclic geometry has yet to be observed experimentally. We use a combination of ultrafast electron diffraction and excited state wavepacket simulations to image structural dynamics through the pericyclic minimum of a photochemical electrocyclic ring-opening reaction in the molecule {\alpha}-terpinene. The structural motion into the pericyclic minimum is dominated by rehybridization of two carbon atoms, which is required for the transformation from two to three conjugated {\pi} bonds. The {\sigma} bond dissociation largely happens after internal conversion from the pericyclic minimum to the electronic ground state. These findings may be transferrable to electrocyclic reactions in general., Comment: Combined manuscript and supplementary information

Superconductivity and charge density waves (CDW) are competitive, yet coexisting orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scales is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa$_{2}$Cu$_{3}$O$_{6+x}$ following the quench of superconductivity by an infrared laser pulse. We observe a non-thermal response of the CDW order characterized by a near doubling of the correlation length within $\approx$ 1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDW manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations., Comment: Accepted version. 34 pages, 11 figures, Main text and Supplementary Materials

We imaged the conformer-specificity of an electrocyclic ring-opening reaction as predicted by the Woodward-Hoffmann rules in real space and time employing a combination of ultrafast electron diffraction and excited state dynamics simulations.

Developing femtosecond resolution methods for directly observing structural dynamics is critical to understanding complex photochemical reaction mechanisms in solution. We have used two recent developments, ultrafast mega-electron-volt electron sources and vacuum compatible sub-micron thick liquid sheet jets, to enable liquid-phase ultrafast electron diffraction (LUED). We have demonstrated the viability of LUED by investigating the photodissociation of tri-iodide initiated with a 400 nm laser pulse. This has enabled the average speed of the bond expansion to be measured during the first 750 fs of dissociation and the geminate recombination to be directly captured on the picosecond time scale.

The IASLC staging and Prognostic Factor Committee proposed new changes to the descriptors for the 8th edition of the Tumour Node Metastasis Staging for Lung Cancer. The T1 descriptor changes include (1) T1 tumours are subclassified into T1a ( 1 cm), T1b ( 1 to 2 cm), T1c ( 2 to 3 cm). The corresponding changes are introduced to the overall staging: T1aN0M0 = Stage IA1; T1bN0M0 = Stage IA2; T1cN0M0 = Stage IA3. (2) The introduction of the pathological entities Adenocarcinoma-In-Situ (AIS), Minimally Invasive Adenocarcinoma, and Lepidic Predominant Adenocarcinoma. The corresponding changes on the T descriptor are as follows: Adenocarcinoma-in situ is coded as Tis (AIS); Minimally Invasive Adenocarcinoma is coded as T1a(mi). In this review, the basis for these changes will be described, and the implications on clinical practice will be discussed.

Hyperbilirubinemia is a known risk factor in patients undergoing open heart operations. Infective endocarditis often leads to valvular injury, such as rupture of chordae tendineae or leaflet perforation, which can cause acute heart failure in association with pulmonary hypertension and liver dysfunction. Here we present a patient with massive liver congestion, reflected by extreme hyperbilirubinemia, secondary to acute heart failure following mitral valve endocarditis that was successfully treated by emergency mitral and tricuspid valve repair.

In situ X-ray synchrotron tomography was used to investigate the stress corrosion cracking behavior of under-aged Al–Zn–Mg–Cu alloy in moisture. The discontinuous surface cracks (crack jumps) mentioned in the literature are actually a single continuous and tortuous crack when observed in three dimension (3D). Contrary to 2D measurements made at the surface which suggest non-uniform crack growth rates, 3D measurements of the crack length led to a much more accurate measurement of crack growth rates.

Tolerogenic dendritic cells (DCs) are crucial for peripheral tolerance mediated by a variety of cytokines, including transforming growth factor-β1 (TGF-β1). We have observed that TGF-β1-treated DCs (TGFβ-DCs) were resistant to the maturation stimulus of lipopolysaccharide (LPS) and that TGF-β1 down-regulated Toll-like receptor 4 (TLR4) expression on DCs. The purpose of this study was to analyze whether TGF-β1 affected the production of cytokines/chemokines and proteins in the TLR4 signal transduction pathway following LPS stimulation. We observed that TGF-β1 induced a significant increase in interleukin (IL)-10, impaired IL-12 secretion, and attenuated messenger RNA (mRNA) expression of chemokines CCL2, CCL3, and CXCL10 in DCs following LPS administration. We also noted that TGF-β1 suppressed LPS-induced activation of nuclear factor (NF)-κB, extracellular signal-related kinases (ERK)-1/2, and p38 in DCs. Taken together, our results identified the suppressive effects of TGF-β1 on TLR4 signal transduction, strengthening the notion that TGFβ-DCs are a unique type of tolerogenic DC exhibiting distinct characteristics.

This study shows that a spatially modulated sinusoidal electric field can significantly tune the magneto-absorption spectra of a graphene ribbon. The pattern of absorption spectra evolves with the amplitude of electric potential (V0). When V0 is weaker than the state energy of the first Landau level, E1, the modulated electric field not only changes the peak intensity and peak position of the absorption lines, but also generates new peaks. These additional peaks follow the unusual optical selection rule. When V0 is stronger than E1, the intensity of original peaks, induced by the uniform magnetic field, shrinks, and an anomalous lowest peak appears. Most importantly, the energy position of the first peak strongly depends on both the amplitude of the electric potential and the strength of the magnetic field. These characteristics can be used to modulate the threshold frequency of the magneto-absorption spectra.

The effect of natural killer (NK) cell alloreactivity on the outcome of unrelated hematopoietic SCT (HSCT) remains a topic of debate. NK cell alloreactivity after allogeneic HSCT is regulated by killer-cell Ig-like receptors (KIRs). To investigate the influence of KIRs on outcome after unrelated HSCT, we retrospectively analyzed the HLA and KIR genotypes of 116 donor-recipient pairs. We found that missing KIR ligands in recipients were significantly associated with a decreased leukemic relapse risk (P=0.019, HR=0.329), mainly in myeloid disease (P=0.003, HR=0.193). This beneficial effect was seen in AML/myelodysplastic syndrome and also in chronic myeloid leukemia. In myeloid disease, missing KIR ligands also improved 5-year OS (P=0.034, HR=0.430) and disease-free survival (DFS) (P=0.024, HR=0.445). Meanwhile, the presence of donor-activating KIR2DS3 gene was associated with increased relapse risk (P=0.003, HR=5.046), decreased OS (P=0.004, HR=3.181) and DFS (P=0.003, HR=2.919) in myeloid disease. No effect was seen in patients with lymphoid disease. Our study indicated that, in unrelated HSCT for myeloid leukemia, missing KIR ligands in recipients offered a lower relapse risk and a long-term survival advantage. The presence of KIR2DS3 in the donor was an important risk factor for myeloid leukemia.

A series of polydimethylsiloxane-containing elastomers (S elastomers) were synthesised from 4,4′-diphenylmethane diisocyanate (MDI), 1,4-butanediol (1,4-BD) and polydimethylsiloxane (PDMS). Through TGA analysis, S elastomers exhibited a four-stage degradation. The first and second stages resulted from the degradation of hard segment; the complicated degradation behaviour in the stages is associated with two hard-segment structures in the S elastomers. The third stage was the decomposition of PDMS, in which a cyclosiloxane degradation product was formed; subsequently, at a higher temperature it proved to be macrocyclics, which were degraded in the vicinity of 550 °C. Obviously, the degradation of S elastomers differed from the two-stage degradation of conventional polyurethane. Compared to conventional polyurethane, S elastomers presented better mechanical properties, showing the strength and elongation at break about 5.6~20.6 MPa and 550~830 %, respectively. With the better mechanical properties of S elastomers, nano-structured fibre mats were produced by electrospinning. Fibre morphology was observed by SEM and the effects of processing variables, including solution concentrations and voltages, on the morphology were evaluated.

The low energy magnetoelectronic structures for a nanographene ribbon under modulated magnetic fields are investigated through the Peierls tight-binding model. They are dominated by the field strength, period, phase, the ribbon width, and edge structure. The modulated magnetic field could add state degeneracy, modify energy dispersions, alter subband spacings, affect carrier-density distributions, create additional band-edge states, and extend the partial flat bands. The main features of energy bands are directly reflected in density of states, such as the position, the height, the structure, and the number of the prominent peaks. These results are compared with a zigzag ribbon under a uniform magnetic field. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Imide-containing siloxane-urethane copolymers (I-PU copolymers) were synthesized from 4,4'-diphenylmethane diisocyanate (MDI), OH-terminated polydimethylsiloxane (PDMS) and pyromellitic dianhydride (PMDA). The hard segment consisted of urethane and imide segments and the soft segment was PDMS. The DSC of I-PU copolymers suggests that they had a high degree of phase separation in their low hard segment contents and phase mixing in high hard segment contents. DMA indicates similar phase behaviour and shows that incorporating imide segments into the copolymers can maintain the high modulus at high temperature. The progress of degradation of I-PU copolymers was determined by TGA and standard kinetics methods and there were three stages at around 250~425 °C, 425~560 °C and 560~700 °C, respectively. The first stage was dominated by the hard-segment structure and content. Incorporating imide segments into PU raises the characteristic temperatures of degradation in the first stage. The second stage resulted from the degradation of the PDMS soft segment to form oligomers by the interchange reaction. The degradation of the imide segment leads to the third stages because the maximum rate of degradation in DTG curves increases with the imide content.

An 8-week feeding trial was conducted to determine two vitamin C derivatives, L-ascorbyl-2-sulphate (C2S) and L-ascorbyl-2-polyphosphate (C2PP), to satisfy vitamin C requirement and to test their effects on the non-specific humoral immune responses of juvenile grouper, Epinephelus malabaricus. C2S and C2PP were each supplemented at 20, 50, 80, 150, 250 and 400 mg kg(-1) diet in the semi-purified basal diet providing of 7, 16, 28, 55, 86, 142 mg ascorbic acid (AA) equivalent of C2S kg(-1) diet and 4, 9, 15, 31, 49, 75 mg AA equivalent of C2PP kg(-1) diet, respectively. Basal diet without AA supplemented was included as a control. Each diet was fed to triplicate groups of grouper (mean initial weight: 6.69 +/- 0.07 g). Fish fed diets with greater than or equal to 28 mg AA equivalent of C2S or greater than or equal to 4 mg AA equivalent of C2PP kg(-1) had significantly (P < 0.05) greater weight gain (WG) than fish fed the unsupplemented control diet. Liver AA concentrations were higher in fish fed diets with greater than or equal to 16 mg AA equivalent of C2S or greater than or equal to 9 mg AA equivalent of C2PP kg(-1) than fish fed the control diet. Alternative pathway of complement activation (ACP) was higher in fish fed diets with greater than or equal to 55 mg AA equivalent of C2S or greater than or equal to 15 mg AA equivalent of C2PP kg(-1) than fish fed the control diet. Lysozyme activity was higher in fish fed greater than or equal to 86 mg AA equivalent of C2S or greater than or equal to 15 mg AA equivalent of C2PP kg(-1) than fish fed the control diet. Analysis by broken-line regression of WG indicated that the adequate dietary vitamin C concentration from each vitamin C derivative in growing grouper is 46.2 mg AA equivalent of C2S kg(-1) diet and 17.8 mg AA equivalent of C2PP kg(-1) diet, and it also indicated that C2S is approximately 39% as effective as C2PP in meeting the vitamin C requirement for grouper. The data suggest that both C2S and C2PP supplementation support non-specific immune responses of grouper.

Two series of siloxane-urethane copolymers were prepared from polydimethylsiloxane (PDMS) with a molecular weight of 1000 or 1800 which was used as a soft segment, 4,4′-diphenylmethane diisocyanate (MDI) and 1,4-butanediol (1,4-BD). Differential scanning calorimetry (DSC) demonstrated that the position (Tgs) and breadth (ΔB) of soft-segment glass transition of copolymers remained constant as the hard-segment content increased. Heat capacities at soft-segment glass transition of the copolymer (ΔCp) were 0.195∼0.411 J/g○C and heat capacities of pure PDMS (ΔCp0) were 0.571∼0.647 J/g○C, leading to the various ΔCp/ΔCp0 ratios. The ΔCp/ΔCp0 ratios decreased as the increasing of hard-segment content, showing poor phase separation. The FTIR spectrum confirmed the occurrence of hydrogen bonding in ether end-group of pure PDMS. The ether group of the soft segment led to interfacial mixing between soft and hard segments. The tan δ of the soft segment determined by dynamic mechanical testing (DMA) also identified the mixing of soft and hard segments. The mechanical properties of the copolymer were directly related to either the soft and hard segment contents or the chain lengths of soft and hard segments. The hard segment that reinforced the soft segment and interfacial thickness between soft and hard segment dominated the mechanical properties.

An 8-week feeding trial was conducted to evaluate two vitamin C derivatives, L-ascorbyl-2-monophosphate-Mg (C2MP-Mg) and L-ascorbyl-2-monophosphate-Na (C2MP-Na), to satisfy the vitamin C requirement and to test their effects on the immune responses of juvenile grouper, Epinephelus malabaricus. C2MP-Mg and C2MP-Na were each supplemented at 20, 50, 80, 150, 250, and 400 mg kg−1 diet in the basal diet providing of 7, 18, 31, 51, 93, 145 mg ascorbic acid (AA) equivalent of C2MP-Mg kg−1 diet and 4, 10, 17, 31, 47, 77 mg ascorbic acid (AA) equivalent of C2MP-Na kg−1 diet, respectively. Basal diet without AA supplementation was included as control. Each diet was fed to triplicate groups of grouper (mean initial weight 3.20 ± 0.05 g). Fish fed diets supplemented with either C2MP-Mg or C2MP-Na had significantly (P

We present the spectrum of baryons in $SU(4)$ gauge theory with fundamental fermion constituents, which is of significant interest for composite dark matter model building. We first compare the spectra and properties of baryons in $SU(3)$ and $SU(4)$ gauge theories (in which they are fermionic and bosonic, respectively) and then compute the cross section for direct detection of dark matter via Higgs boson exchange for TeV-scale composite dark matter arising from a confining $SU(4)$ gauge sector. Comparison with the latest LUX results leads to tight bounds on the fraction of the mass of the constituent fermion that may arise from electroweak symmetry breaking. Lattice calculations of the dark matter mass spectrum and the Higgs--dark-matter coupling are performed on quenched ${16}^{3}\ifmmode\times\else\texttimes\fi{}32$, ${32}^{3}\ifmmode\times\else\texttimes\fi{}64$, ${48}^{3}\ifmmode\times\else\texttimes\fi{}96$, and ${64}^{3}\ifmmode\times\else\texttimes\fi{}128$ lattices with three different lattice spacings, using Wilson fermions with moderate to large pseudoscalar meson masses. Our results lay a foundation for future analytic and numerical studies of composite baryonic dark matter.

Background and objective: In addition to the standard antiepileptic drugs, traditional Chinese medicines (TCMs) are used for the treatment of epilepsy in oriental countries. The interactions between antiepileptic drugs and TCMs represent a potential problem in clinical application. Because valproic acid (VPA), one of the most widely prescribed antiepileptic drugs, may be administered concomitantly with Paeoniae Radix (PR), one of the famous TCMs, in some epileptic patients, the present study was conducted to evaluate the influences of PR on the pharmacokinetics of VPA. Method: The pharmacokinetics of VPA were investigated in a randomized, open-label, two-way crossover study. Six healthy volunteers received the following treatments in a crossover design: (i) 1·2 g extract powder of Paeoniae Radix once daily for 7 days and one 200 mg VPA gastro-resistant tablet on day 7 and (ii) one 200 mg VPA gastro-resistant tablet alone on day 7. Serial plasma samples were obtained on day 7. Total and free (unbound) VPA plasma concentrations were determined by fluorescence polarization immunoassay (FPIA). Safety measures included laboratory tests (haematology, serum chemistry and urinalysis) and adverse event monitoring. Statistical comparisons of pharmacokinetic parameters were performed with the Student paired t-test. Results: Overall clinical safety was satisfactory. The mean maximum plasma concentration of VPA was attained at within 6 h after oral administration of VPA alone and 3–4 h after oral administration of VPA in combination with PR. The plasma level of VPA declined with a half-life of 11·71 and 11·91 h, respectively. No statistically significant difference was obtained in any of the pharmacokinetic parameters (Tmax, Cmax, AUC, t1/2, MRT, CL/F and Vd/F) of VPA between the two treatments. Also, there was no significant difference in the protein binding rates of VPA. Conclusion: PR did not significantly affect the absorption, distribution, metabolism and elimination of VPA in healthy volunteers.

The optical properties of well-aligned multiwalled carbon nanotube bundles are studied within the gradient approximation. The imaginary ~real! part of the transverse dielectric function exhibits a special peak ~dip! at frequency v;2g0 ~g0 is the nearest-neighbor overlap integral!. Consequently the loss function shows a prominent p-plasmon peak at v.2g0 . The p plasmon also induces a strong and abrupt edge in the reflectance spectrum. These features are similar to those of graphite. The optical properties are hardly affected by the chiral angle of carbon nanotube; moreover, they are insensitive to small variation in the radius of carbon nanotube. On the other hand, the optical properties strongly depend on the polarization direction of an external electric field. The well-aligned multiwalled carbon nanotubes with high radius uniformity, which were recently reported by Fan et al. @Science 283, 512 ~1999!#, could be used to verify the predicted optical properties.

A simple and rapid capillary electrophoretic method was developed for the simultaneous determination of honokiol and magnolol in Magnolia officinalis extracts and dextrorphan was used as the internal standard. The running buffer was composed of 22.5 mM Na2HPO4 and 10 mM Na2B4O7 (pH 9.1–9.2). The linear calibration range was 2 – 20 μg/mL for honokiol and 5–50 μg/mL for magnolol. It was found that 0.95 ±0.02 mg of honokiol and 4.37 ± 0.08 mg of magnolol were contained in the ethanol (50%) extracts of 1 g of Magnolia officinalis. The contents of these two active principles in Magnolia officinalis was successfully determined within 12 min.

Introduction We aimed to evaluate regeneration of injured temporomandibular joint (TMJ) discs following reconstituted collagen template implantation in rabbits using contrast-enhanced magnetic resonance imaging (MRI) and to correlate these findings with histology. Methods Twenty-four adult rabbits were divided into five groups: group A, partial discectomy without implantation ( n = 6); group B, partial discectomy with collagen template implantation ( n = 6); group C, partial discectomy with subdermal graft implantation ( n = 6); group D, sham operation ( n = 4); and group E, control ( n = 2). All rabbits received baseline MRI scans before surgery and follow-up MRI studies at 3 months after surgery. All rabbits were sacrificed for histologic analysis after the follow-up MRI. Results In group A, follow-up MRI showed marked joint effusion in all six injured TMJs, which was accompanied by bony erosion at the tympanic fossa and mandibular condyle. In group B, MRI showed a homogenous low signal intensity in five of six discs, suggestive of regeneration. One disc showed higher signal intensity at its lateral portion than that of the original disc, indicating partial regeneration. MRI of group C depicted a low signal intensity, bandlike regenerative structure in four of the six discs. One disc with partial regeneration demonstrated relatively high signal intensity. The disc in the sixth animal of this group showed no evidence of regeneration. All of the MRI findings were in agreement with the histologic findings. Conclusion TMJ discs can regenerate following implantation of a reconstituted collagen template in discectomied rabbits. Contrast-enhanced MRI can be used to monitor and determine the degree of disc regeneration.

The crisis level in the worldwide suicide rate has revealed a severe suicide problem in Taiwan that is now well above the world average of 16 per 100,000 individuals. Many countries have relied on suicide care volunteers training programmes to conduct suicide prevention programmes. However, there is a dearth of research evaluating the effect of volunteers on psychological distress and the impact of volunteer experience level. An evaluation of the impact of experienced and novice volunteers in alleviating psychological distress of suicide survivors was conducted. A supervised programme trained 15 volunteers at Years 1 and 2. Year 1 volunteers completed 400 h of service with continuing education. Programme evaluation occurred after Year 2 volunteers had completed training. Eighty-two suicide survivors were recruited. With 60 suicide survivors completing 3 month of volunteer care, a significant group difference with time interaction in suicide survivors who exhibited moderate to severe distress between the veteran care and novice care groups was found. Compared with novice volunteers, veteran volunteers with at least 1 year of experience are more effective with suicide survivors reporting higher psychological distress.

Aberrant regulation in the adhesive ability of cancer cells is closely associated with their metastatic activity. In this study, we examine the role of ErbB-2 in regulating the adhesive ability of androgen receptor (AR)-positive human prostate cancer (PCa) cells, the major cell population of PCa. Utilizing different LNCaP and MDA PCa2b cells as model systems, we found that ErbB-2 activity was correlated with PYK2 activity and adhesive ability in those cells. Increased ErbB-2 expression or activity in LNCaP C-33 cells enhanced PYK2 activation and cell adhesion, while the high PYK2 activity and the rapid adhesion of LNCaP C-81 cells were decreased by diminishing ErbB-2 expression or activity. Knockdown studies revealed the predominant role of ErbB-2 in regulating LNCaP C-81 cell adhesion. Coimmunoprecipitation showed that C-81 cells had increased interaction between ErbB-2 and PYK2. Elevated ErbB-2 activity in LNCaP cells correlated with increased ERK/MAPK activity and enhanced adhesive ability, which were abolished by the expression of K457A-PYK2 mutant or the treatment of PD98059, a MEK inhibitor. In summary, our data suggested that ErbB-2, via PYK2-ERK/MAPK, upregulates the adhesive ability of AR-positive human PCa cells.

An outbreak of pyoderma caused by methicillin-susceptible Staphylococcus aureus occurred in a nursery for newborns over 26 days. During this period, six neonates were involved. The mother of the first case had trunk pyoderma before delivery, which was regarded as the source of the outbreak. Contamination of the environment and equipment were implicated as the reservoirs of further pathogen spread, as supported by pulsed-field gel electrophoresis (PFGE) results, which showed that some screening isolates were indistinguishable from the epidemic strain. Termination of the outbreak was achieved by the reinforcement of infection control practices and disinfection of environmental surfaces.

A new helium gas bearing turboexpander of a helium refrigeration system used for space environment simulation experiments is described in this paper. The main design parameters and construction type of some key parts are presented. An improved calculation of thermodynamic efficiency and instability speed of this turboexpander has been obtained by a multiple objects optimization program. Experiments of examining mechanical and thermodynamic performance have been repeatedly conducted in the laboratory by using air at ambient and liquid nitrogen temperature, respectively. In order to predict the helium turboexpander performance, a similarity principles study has been developed. According to the laboratory and on-the-spot experiments, the mechanical and thermodynamic performances of this helium turboexpander are excellent.

Understanding cell proliferation regulation in hormone refractory prostate cancer may provide answers for novel solutions. Protein tyrosine phosphatases have been thought to have key roles in regulating cell proliferation and be involved in oncogenesis, although to our knowledge their functional roles in human prostate cancer remain unknown. Human prostatic acid phosphatase (PAcP), a major phosphatase in prostate epithelium, has been shown to function as a neutral protein tyrosine phosphatase in these cells. We evaluated the biological significance of cellular prostatic acid phosphatase expression in human prostate cancer cells.Immunohistochemical testing of human prostate cancer archival specimens was done to evaluate the expression of cellular PAcP. Immunoprecipitation and immunoblotting were performed to determine cellular PAcP and SH2 domain-bearing tyrosine phosphatase-1 levels as well as tyrosine phosphorylation of c-ErbB-2/neu in different human prostate cancer cells. The biological behavior of LNCaP derivative sublines was characterized in vitro and in vivo by soft agar analysis and xenograft animal inoculation.Immunohistochemical staining of human prostate clearly showed that cellular levels of PAcP significantly decreases in prostate cancer cells (p0.001). The results of biochemical characterization revealed that the cellular level of PAcP but not SHP-1, another differentiation associated protein tyrosine phosphatase, consistently correlated negatively with the growth of several human prostate cancer cell lines. Reintroducing cellular PAcP activity in prostate cancer cells by PAcP complementary DNA transfection resulted in decreased tyrosine phosphorylation of c-ErbB-2/neu, decreased proliferation rates in culture as well as decreased anchorage independent growth in soft agar. The xenograft animal model demonstrated that a higher tumor growth rate as well as larger size is associated with a lower level of cellular PAcP.Cellular PAcP can down-regulate prostate cancer cell growth, at least partially by dephosphorylating c-ErbB-2/neu. Therefore, decreased cellular PAcP expression in cancer cells may be involved in prostate cancer progression.

Background: Phenytoin (PHT), one of the most widely prescribed antiepileptic drugs, has been reported to be associated with numerous drug–drug interactions. However, there are far fewer reports about the pharmacokinetic interactions between PHT and traditional Chinese medicines (TCMs). Paeoniae Radix (PR), one of the well-known TCMs, is used as an adjunct in some epileptic patients. Objective: In the present work, we studied the influences of PR on the pharmacokinetics of PHT in rats to identify the possible interactions between PR and PHT. Method: A single dose of PHT (100 mg/kg) alone or in combination with PR extract (300 mg/kg) was administered by gavage to male SD rats. Serial blood samples of PHT were obtained for up to 24 h post-administration and measured by high-performance liquid-chromatography. The free (unbound) plasma concentrations of PHT were determined by fluorescence polarization immunoassay. The plasma concentrations were used to construct pharmacokinetic profiles by plotting drug concentration–time curves. All data were subsequently processed by the computer program WINNONLIN. Statistical comparisons of pharmacokinetic parameters were performed with the unpaired Student t-test. Results: The mean maximum plasma concentration of PHT was attained 2 h after oral administration of PHT alone and 4–6 h after oral administration of PHT in combination with PR. The plasma level of PHT declined with a half-life of 5˙38 h after PHT alone and 4˙03 h after PHT and PR given together. No statistically significant differences were obtained in most of the pharmacokinetic parameters (Cmax, AUC, t1/2, MRT and CL/F) and protein binding rates of PHT between the two treatments. However, significant differences in Tmax and Vd/F between groups were noted. Conclusion: The significant increase in Tmax indicated that simultaneous oral administration of PR delayed the absorption of PHT. The delayed absorption of PHT might lead to its slow onset of clinical effect. There were no significant differences in Cmax, AUC, t1/2, MRT and CL/F of PHT between the two groups, showing that PR could not significantly affect the extent of absorption, metabolism and elimination of PHT. No significant difference in protein binding rate was found, indicating that PR might not significantly alter the protein binding of PHT. While a significant decrease in Vd/F was noted, the mechanism underlying the apparently decreased Vd/F of PHT influenced by PR needs further study.

In clinical application, cefepime and cyclosporine are regularly combined in the treatment of organ transplant patients, so the interaction of these two drugs can be hypothesized. Therefore, the pharmacokinetics of cefepime alone and in combination with cyclosporine in rat using microdialysis coupled with HPLC-UV on-line system was evaluated in the study. Cefepime at three doses (20, 50, and 100 mg/kg) showed linear kinetics. After addition of cyclosporine, the mean residence time was increased from 34.9 min to 48.6 min (p0.05, n=6), and the area under the concentration versus time curve (AUC) increased from 4775 min microg/ml to 6960 min microg/ml (p0.01, n=6). While in the brain, AUC increased from 64.3 min microg/ml to 110.2 min microg/ml. In summary, cyclosporine (20 mg/kg) could significantly alter the simultaneously administered cefepime (50 mg/kg) unbound drug pharmacokinetic parameters in both blood and brain.

Bacteremia is a major cause of death in renal transplant recipients. However, an understanding of the clinical spectrum of bacteremia post kidney transplantation in Taiwan is lacking. This study was undertaken in an attempt to analyze the causative organisms, the sites of primary infection, and the possible significant determinants of mortality.Eighty-six positive blood cultures from renal transplant recipients were seen at the Taichung Veterans General Hospital from August 1993 to April 1999. Sixty blood cultures obtained from episodes that occurred in 43 kidney recipients were regarded as significant and included. All the data were obtained by reviewing medical records.Forty-six episodes (76.7%) of bacteremia happened 6 months after transplantation. Gram-negative bacilli accounted for 73.3% (44/60) of the cases of bacteremia. Escherichia coli, constituting 26.7% (16/60) of the etiologic agents, was the most common pathogen. In 50.0% of all episodes, urinary tract infection was the main cause of bacteremia. The overall mortality rate in this series was 16.7%. Risk of death seemed higher if bacteremia occurred with a primary site of infection other than the urinary tract (26.7% vs 6.7%) and after methylprednisolone pulse therapy (33.3% vs 12.5%), though both correlations were not statistically significant.This study may shed light on the empirical therapy and better management needed for treating bacteremia in renal transplant recipients in Taiwan and provide a nidus for further prospective surveys.

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague—Dawley rats. Cefoperazone (50 mg kg−1, i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL−1. Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were ≤ 10% in the range of 0.05–10 μg mL−1. The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7.8%. It is concluded that cefoperazone is capable of penetrating the blood—brain barrier.

Receptor protein tyrosine phosphatase alpha (RPTPalpha) is a transmembrane protein phosphatase, and has been proposed to be involved in the differentiation of the neuronal system. In the present study, we demonstrated the expression of RPTPalpha mRNA in several normal human tissues. We further investigated the regulation of expression of RPTPalpha mRNA in epithelial cells utilizing three commercially available human prostate cancer cell lines LNCaP, PC-3 and DU145. This is because these cells exhibit different levels of differentiation, defined by the expression of a tissue-specific differentiation antigen, prostatic acid phosphatase (PAcP), and their androgen sensitivity. LNCaP cells express PAcP and are androgen-sensitive cells, while PC-3 and DU145 cells do not express PAcP and are androgen-insensitive cells. Northern blot analyses revealed that, in LNCaP cells, fetal bovine serum (FBS) and 5alpha-dihydrotestosterone (DHT) down-regulates RPTPalpha mRNA expression, similar to the effect on PAcP. Contrarily, FBS up-regulated the RPTPalpha mRNA level in PC-3 and DU145 cells. In LNCaP cells, sodium butyrate inhibited cell growth and up-regulated RPTPalpha as well as PAcP mRNA expression. Although, sodium butyrate also inhibited the growth of PC-3 and DU145 cells, the level of RPTPalpha mRNA was decreased in PC-3, while increased in DU145 cells. Thus, data taken together indicate that the expression of RPTPalpha is apparently regulated by a similar mechanism to that of PAcP in LNCaP cells.

Objective: Studies on antiepileptic drug utilization are important for the optimization of drug therapy and drug control. The present study was to evaluate the drug utilization pattern of standard antiepileptic drugs and traditional Chinese medicines (TCMs) in the treatment of different types of epilepsy in a general hospital in Taiwan. Method: The epileptic patients under antiepileptic drug treatment at Veterans General Hospital-Taipei were considered in the analysis. Current diagnosis was obtained by the neurologist in charge of the patient. All patients were interviewed by standard questionnaire designed to provide specific information on the types of antiepileptic drugs and details of their use. The questionnaire also sought to determine whether TCMs were used, and whether patients were using TCMs in combination with hospital standard treatment. The results were analysed by descriptive statistics. Results: 729 patients with epilepsy definitely diagnosed were analysed in the study. 445 patients (61·04%) were prescribed with one antiepileptic drug. Combinations of two antiepileptic drugs were prescribed to 261 patients (35·80%), and combinations of three or more antiepileptic drugs to 23 patients (3·16%). A total of 1039 antiepileptic drugs was prescribed, corresponding to an average 1·42 drugs per patient. The most frequently prescribed antiepileptic drug was carbamazepine (56·93%), followed by phenytoin (31·96%), valproate (30·73%) and clonazepam (14·13%). Among the 729 epileptic patients, 83·68% used standard antiepileptic drugs alone, 16·32% used antiepileptic drugs in combination with TCMs. Conclusion: Monotherapy is the type of therapy most frequently used in all types of seizures. The selection of antiepileptic drugs is based on efficacy for specific seizure types and epileptic syndromes. The most frequently prescribed antiepileptic drug was carbamazepine, followed by phenytoin, valproate and clonazepam. As some of the patients used TCMs for treatment of epilepsy even when scientific medicine has been provided, further studies on the possible interactions between TCMs and antiepileptic drugs are in progress.

From 1993 to 1998, 29 pyogenic psoas abscesses occurring in 27 patients were seen in Taichung Veterans General Hospital. Their age range was 25 to 85 years. Diabetes mellitus was the leading underlying disease. Fever and pain in the flank area, back and hip were the usual manifestations. The duration of symptoms prior to the diagnosis ranged from 3 days to 6 months. Most abscesses were diagnosed by computed tomography (CT) images and proven by abscess cultures, which were divided into primary and secondary types. Eighteen of 29 abscesses were regarded as primary. Staphylococcus aureus was the most common pathogen in the primary abscesses, followed by Streptococcus agalactiae, Escherichia coli, viridans streptococci, S. epidermidis, and Salmonella spp.. In the secondary abscess category, E. coli was the leading organism in this series, followed by S. aureus, Klebsiella pneumoniae, viridans streptococci and Candida albicans. The associated conditions included epidural abscess, osteomyelitis, septic arthritis, perirenal abscess, pulmonary tuberculosis, empyema, hydronephrosis and trauma history. The initial empiric therapy comprised mostly of cefazolin or oxacillin with or without an aminoglycoside. Thirteen patients underwent percutaneous drainage, while six received surgical debridement, including two with a recurrent abscess. One patient had both drainage and debridement. Others received medical treatment only. Two of the patients with primary abscess died in spite of percutaneous drainage. Therefore, open drainage, besides appropriate antibiotic treatment, is still required to control complex abscesses with sepsis.

A renal abscess, caused by Serratia marcescens with endophthalmitis in a 68-year-old diabetic female, is described. Endophthalmitis presented with visual loss, conjunctiva injection and lid edema with eye pain. Right costovertebral knocking pain was also noted. Sonography and computed tomography of abdomen showed a 4 cm hypoechoic lesion in the middle portion of the right kidney with marginal enhancement after contrast media injection. Percutaneous abscess drain was performed. Pus culture from the drain tube revealed S. marcescens, yet, vitreous cultures yielded no growth, which was ascribed to previous antibiotics use. Although vitrectomy, fortified eye drops, intravitreal and systemic intravenous antibiotics were administered, the visual function was still lost. To our knowledge, this is the first reported case of S. marcescens renal abscess complicated with endophthalmitis.

To compare prescribing patterns between the elderly and nonelderly in 1994, to disclose prescribing trends in the elderly-between 1992 and 1994, to explore whether drug utilization is in agreement with disease prevalence, and to identify suboptimal prescribing by drug category for ambulatory elderly patients.Cross-sectional survey at two separate time intervals.All public group practice centers (GPCs) in Taiwan.Ambulatory adults who visited GPCs during 1 random week. Those 65 years or over were classified as the elderly group, and those 20-64 years were the nonelderly group.Mean diagnosis, drug use, and expenditure; frequency of diagnosis; and prescribing by therapeutic category.Data on 30777 elderly and 38184 nonelderly patients were collected in 1994. There was widespread use of antacids. Compared with nonelderly adults, the elderly were diagnosed with more diseases (1.3 vs. 1.2, respectively; p0.01), received more medications (4.7 vs. 4.1, respectively; p0.01), and had higher drug expenditures (5.4 vs. 4.6, respectively; p0.01). Chronic illness was more prevalent in the elderly, which accounted for the extensive use of cardiovascular drugs (32.1%), nonsteroidal antiinflammatory drugs (25.9%), and anxiolytics (15.9%). The upward trend in the elderly from 1992 to 1994 with hypertension (18.6% vs. 20.0%) or diabetes (9.2% vs. 10.9%) did not result in more cases of cerebrovascular disease (7.1% vs. 4.9%). There was a substantial increase in use of antispasmodic and gastroprokinetic agents (4.5% to 10.7%); the use of antacids decreased (73.6% to 63.4%) in the elderly.Compared with the prevalence of disease, there was extensive nonspecific use of anxiolytics and antacids. However, lessened use of antidepressants and postmenopausal hormone replacement may have an impact on morbidity and mortality and deserves particular attention.

We determined that the larval nervous system of Ilyanassa obsoleta contains paired cerebral, pleural, pedal, buccal and intestinal ganglia and unpaired apical, osphradial, and visceral ganglia. We used a modified form of NADPH diaphorase histochemistry to compare the neuroanatomy of precompetent (including specimens 6, 8, and 12 days after hatching), competent, and metamorphosing larvae with postmetamorphic juveniles. This method highlighted ganglionic neuropils and allowed us to identify individual ganglia at various stages of development, thereby laying a foundation for concurrent histochemical studies. The first ganglia to form were the unpaired apical and osphradial ganglia and the paired cerebral and pedal ganglia. In larvae 6 days after hatching, the neuropil had already appeared in the apical and osphradial ganglia. Neuropil began to be apparent in the cerebral and pedal ganglia 2 days later. At that time, the pleural and buccal ganglia were identifiable and adjacent to the posterior edge of the cerebral ganglia. The ganglia of the visceral loop were concurrently recognizable, although the supraintestinal ganglion developed slightly earlier than the subintestinal and visceral ganglia. By 12 days after hatching all of the major adult ganglia were discernible. The apical ganglion was retained by newly metamorphosed juveniles, but not by juveniles 2 days later. After metamorphosis was complete, the central nervous system (CNS) was consolidated into its juvenile form with ipsilateral cerebral and pleural ganglia being partially fused. The metamorphic translocation of ganglia, which included a caudal relocation of the cerebrals and the migration of the buccals from above the esophagus to a position below it, correlated with the movement of the proboscis to the dorsal part of the head.

Gaseous nitric oxide (NO) is produced through the action of the enzyme nitric oxide synthase (NOS) and acts as a neurotransmitter (Jacklet and Gruhn, 1994b. Elphick et al., 1995a; Jacklet, 1995) in the nervous systems of adult gastropod molluses. By comparison, little or no information appears to exist about the ontogeny of molluscan NOS-containing neurons. NADPH-diaphorase (NADPHd) has been determined biochemically and histochemically to colocalize with NOS immunoreactivity in neurons; NOS is an isoform of NADPHd (Dawson et al., 1991; Hope et al., 1991). We used NADPHd histochemistry to map the distribution of NOS activity in the nervous systems of larvae, including metamorphosing individuals, and juveniles of the marine snail Ilyanassa absoieta. Several ganglionic neuropils displayed reaction product throughout development. The most intense NADPHd staining occurred in the neuropil of the apical ganglion, a specialized larval structure. Intermediate staining levels occurred in neuropils of the cerebral, pedal, and pleural ganglia. Larval buccal and intestinal ganglia showed little reaction product, with slight increases arising in metamorphically competent larvae. NADPHd activity conspicuously decreased in the central nervous systems of metamorphosing larvae. The osphradial ganglion, which was present in young larvae, showed only weak NADPHd activity. Our results provide evidence for the existence of a nitrergic signalling system in molluscan larvae and juveniles.

An intravaginal foreign body of long duration can pose a diagnostic dilemma, since a number of diagnostic modalities may fail to detect its existence. We present the case of an 8-year-old girl who suffered from a bloody, malodorous vaginal discharge for over 4 years, during which time she had been evaluated by several gynecologists. A vaginal examination performed under analgesia revealed a pinpoint-sized opening 2 cm above the hymen. We inserted a cannula and injected radio-opaque contrast medium. An intravaginal filling defect was visible, which strongly suggested the presence of a foreign body. An incision through this scarred area was performed and two foreign bodies, one shaped like a plastic tube and the other a cap, were removed. We conclude that vaginography may provide an alternative diagnostic tool for this condition.