A validation study of the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) for patients with chronic low back pain (verification of reliability,validity, and reproducibility)

Introduction  

We developed the Brief Scale for Psychiatric problems in Orthopaedic Patients (BS-POP) (doctor and patient versions). The present study aimed to proactively verify the factorial validity, internal consistency, criterion-related validity and reproducibility of the BS-POP with regard to chronic low back pain patients.     

Protein kinase C β inhibition ameliorates experimental mesangial proliferative glomerulonephritis

Aim: Activation of protein kinase C (PKC) has been implicated in the pathogenesis of diabetic nephropathy where therapy targeting the β isoform of this enzyme has been examined. However, PKC‐β is also increased in various forms of human glomerulonephritis, including IgA nephropathy. Accordingly, we sought to examine the effects of PKC‐β inhibition in the Thy1.1 model of mesangial proliferative glomerulonephritis. Methods: Following administration of monoclonal OX‐7, anti‐rat Thy‐1.1 antibody, Male Wistar rats were randomized to receive either the PKC‐β inhibitor, ruboxistaurin (10 mg/kg per day in chow) or vehicle. Animals were then examined 6 days later. Results: PKC‐β inhibition was associated with reductions in mesangial cellularity and extracellular matrix deposition. Proteinuria was, however, unaffected. In vitro, PKC‐β inhibition showed modest, dose‐dependent reductions in mesangial cell ³H‐thymidine and ³H‐proline incorporations, indices of cell proliferation and collagen synthesis, respectively. Conclusion: The amelioration of the pathological findings of experimental mesangial proliferative glomerulonephritis by PKC‐β inhibition suggests the potential clinical utility of this approach as a therapeutic strategy in non‐diabetic glomerular disease.     

Sodium valproate at therapeutic concentrations changes Ca2+ response accompanied with its weak inhibition of protein kinase C in human astrocytoma cells

Sodium valproate (VPA) has been used clinically for treatment of not only epilepsy but also mood disorder. Although VPA is effective for treatment of epilepsy via inhibition of gamma-aminobutyric acid transaminase, it remains unknown why VPA is effective for the treatment of mood disorder. The authors examined the effect of VPA at therapeutic concentrations (300 and 600 microM) on the elevation of intracellular free calcium concentration ([Ca(2+)](i)) induced by carbachol, a muscarinic receptor agonist, in 1321N1 human astrocytoma cells. Treatment of the cells with 300 and 600 microM VPA for 2 min did not change the carbachol-induced [Ca(2+)](i) elevation. Treatment with 300 and 600 microM VPA for 48 h, however, reduced the elevation. Since we have shown that Li(+) reduced carbachol-induced [Ca(2+)](i) elevation in protein kinase C (PKC)-downregulated 1321N1 cells [Kurita, M., Mashiko, H., Rai, M., Kumasaka, T., Kouno, S., Niwa, S., Nakahata, N., 2002. Lithium chloride at a therapeutic concentration reduces Ca(2+)response in protein kinase C down-regulated human astrocytoma cells, Eur. J. Pharmacol. 442, 17-22.], the activity of PKC was examined. Treatment with VPA at the same concentrations for 24 or 48 h weakly reduced protein kinase C activity in membrane and cytosol fractions from the cells. On the other hand, the treatment of the cells with 600 microM VPA for 24 or 48 h slightly increased the B(max) value, but not the K(d) value, in the binding of [(3)H]quinuclidinyl benzylate, a muscarinic receptor ligand, to the membranes, suggesting that the number or affinity of muscarinic receptor did not decrease after VPA treatment. These results indicate that VPA at therapeutic concentrations slightly decreases the PKC activity and inhibits muscarinic receptor-mediated [Ca(2+)](i) elevation probably through change in the intracellular signaling pathway. VPA-induced reduction of PKC activity and [Ca(2+)](i) elevation may play a role in the treatment of mood disorder.     

Methodology for assessment of renal function

A variety of methods for evaluation of renal function have been discovered, among which glomerular filtration rate (GFR) attracts much attention because of the major determinant of renal function. Recently, novel technique to evaluate glomerular filtration has been developed, including cystatin C, which reflects the changes in GFR at the earlier stage than serum creatinine. Furthermore, a progress has been made in evaluating tubular damage, with the discovery of N-acetyl glucosaminidase and liver-type fatty acid binding protein. More convenient and sensitive methods will be required to assess the changes in renal function in a clinical setting.     

Tranilast ameliorates experimental mesangial proliferative glomerulonephritis

Tissue hypoxia occurs when local metabolism is disturbed by an imbalance between oxygen supply and consumption. In patients with chronic kidney disease, chronic hypoxia in the kidneys is the end result of multiple processes and mechanisms. Once established, however, accumulating evidence points to this chronic hypoxia as the central player and final common pathway to end-stage renal disease. The cellular response to hypoxia is centered on hypoxia-inducible factor, HIF. This factor is composed of two subunits, an oxygen-sensitive HIF-alpha subunit and a constitutively expressed HIF-beta subunit. Intracellular accumulation of HIF induces the coordinated expression of a number of adaptive genes against hypoxic insult.Three isoforms of HIF-alpha subunits have been identified, HIF-1alpha, HIF-2alpha, and HIF-3alpha, of which HIF-2alpha is involved in the regulation of erythropoietin as well as oxidative stress. HIF is regulated by prolyl hydroxylation and asparaginyl hydroxylation of the HIF-alpha subunit at the protein level. Because HIF is activated only to suboptimal levels in various pathogenic states, therapeutic activation holds promise as a novel and effective approach to the future care of end-stage renal disease.     

Disrupted cortical function underlies behavior dysfunction due to social isolation

Stressful events during early childhood can have a profound lifelong influence on emotional and cognitive behaviors. However, the mechanisms by which stress affects neonatal brain circuit formation are poorly understood. Here, we show that neonatal social isolation disrupts molecular, cellular, and circuit developmental processes, leading to behavioral dysfunction. Neonatal isolation prevented long-term potentiation and experience-dependent synaptic trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors normally occurring during circuit formation in the rodent barrel cortex. This inhibition of AMPA receptor trafficking was mediated by an increase of the stress glucocorticoid hormone and was associated with reduced calcium/calmodulin-dependent protein kinase type II (CaMKII) signaling, resulting in attenuated whisker sensitivity at the cortex. These effects led to defects in whisker-dependent behavior in juvenile animals. These results indicate that neonatal social isolation alters neuronal plasticity mechanisms and perturbs the initial establishment of a normal cortical circuit, which potentially explains the long-lasting behavioral effects of neonatal stress.     

π‐Conjugated Polymers Consisting of Isothianaphthene and Dialkoxy‐p‐phenylene Units: Synthesis,Self‐Assembly,and Chemical and Physical Properties

A series of π‐conjugated alternating copolymers consisting of Th‐ITN‐Th and p‐C₆H₂(OR)₂ units were synthesized. XRD indicated that the copolymers assume an interdigitation packing mode, and UV‐Vis spectra revealed a strong tendency for self‐assembly. Upon molecular assembly of the copolymer, the UV‐Vis absorption shifted by about 100 nm to a longer wavelength from that of the single molecule. The copolymers underwent electrochemical oxidation (or p‐doping) and reduction (or n‐doping) at 0.2 and ?2.0 V versus Ag⁺/Ag, respectively. A p‐doped copolymer film showed an electrical conductivity of 182 S · cm^?1, and the temperature dependence of electrical conductivity was measured. The copolymer showed piezochromism and served as a p‐channel material for a field‐effect transistor.

     

A multicenter, double-blind, randomized, placebo controlled trial of infliximab combined with low dose methotrexate in Japanese patients with rheumatoid arthritis

OBJECTIVE: A placebo controlled, double-blind trial (DBT) was conducted for Japanese patients with active rheumatoid arthritis (RA) despite treatment with low dose methotrexate (MTX) to evaluate the efficacy and safety of infliximab. Extended treatment with infliximab was conducted in an open-label trial (OLT). METHODS: In the DBT, 147 patients were randomly assigned and treated with a placebo or 3 mg/kg or 10 mg/kg infliximab at Weeks 0, 2 and 6, combined with MTX. In the OLT, 129 patients from the DBT received 3 mg/kg infliximab every 8 weeks. RESULTS: The mean dose of MTX was 7.2 +/- 2.0 mg/week. Significantly more patients receiving 3 mg/kg (61.2%) and 10 mg/kg (52.9%)infliximab achieved a 20% improvement according to the American College of Rheumatology (ACR) criteria at Week 14, compared to placebo (23.4%) (p < 0.001). There was no significant difference in incidence of adverse events among the treatment groups. In patients receiving infliximab in the DBT, 11.6% of patients with serum infliximab just before the OLT developed antibodies to infliximab (ATI) in the OLT, whereas 62.2% of patients without serum infliximab did. In patients receiving placebo in the DBT, 43.9% developed ATI. CONCLUSION: The efficacy and safety of infliximab combined with low dose MTX were similar to those of the ATTRACT study. The data from the DBT and OLT also supported the importance of an induction treatment of infliximab, followed by a maintenance treatment without a long interval, giving stable serum concentrations in order to prevent formation of ATI.     

Bacteremia and endotoxemia after endoscopic submucosal dissection for gastric neoplasia: pilot study

Background  

Because the invasive procedure of endoscopic submucosal dissection (ESD) entails a large mucosal defect which is left open, with extensive submucosal exposure to the indigenous bacterial flora, the procedure may have a substantial risk for bacteremia. Our aim was to examine gastric ESD-related bacteremia and endotoxemia in gastric neoplasia patients.