Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1.

BACKGROUND: Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood. OBJECTIVE: In this study, we investigate the combined effects of NTP and MCB on PHP in mice. METHODS: NTP and MCB were administered from day 10-29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR. RESULTS: Repeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells. CONCLUSION: These results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs.

P2Y2 receptor-Gq/11 signaling at lipid rafts is required for UTP-induced cell migration in NG 108-15 cells.

Lipid rafts, formed by sphingolipids and cholesterol within the membrane bilayer, are believed to have a critical role in signal transduction. P2Y(2) receptors are known to couple with G(q) family G proteins, causing the activation of phospholipase C (PLC) and an increase in intracellular Ca(2+) ([Ca(2+)](i)) levels. In the present study, we investigated the involvement of lipid rafts in P2Y(2) receptor-mediated signaling and cell migration in NG 108-15 cells. When NG 108-15 cell lysates were fractionated by sucrose density gradient centrifugation, Galpha(q/11) and a part of P2Y(2) receptors were distributed in a fraction where the lipid raft markers, cholesterol, flotillin-1, and ganglioside GM1 were abundant. Methyl-beta-cyclodextrin (CD) disrupted not only lipid raft markers but also Galpha(q/11) and P2Y(2) receptors in this fraction. In the presence of CD, P2Y(2) receptor-mediated phosphoinositide hydrolysis and [Ca(2+)](i) elevation were inhibited. It is noteworthy that UTP-induced cell migration was inhibited by CD or the G(q/11)-selective inhibitor YM254890 [(1R)-1-{(3S,6S,9S,12S,18R,21S,22R)-21-acetamido-18-benzyl-3-[(1R)-1-methoxyethyl]-4,9,10,12,16, 22-hexamethyl-15-methylene-2,5,8,11,14,17,-20-heptaoxo-1,19-dioxa-4,7,10,13,16-pentaazacyclodocosan-6-yl}-2-methylpropyl rel-(2S,3R)-2-acetamido-3-hydroxy-4-methylpentanoate]. Moreover CD and YM254890 completely inhibited Rho-A activation. Downstream of Rho-A signaling, stress fiber formation and phosphorylation of cofilin were also inhibited by CD or YM254890. However, UTP-induced phosphorylation of cofilin was not affected by the expression of p115-regulator of G protein signaling, which inhibits the G(12/13) signaling pathway. This implies that UTP-induced Rho-A activation was relatively regulated by the G(q/11) signaling pathway. These results suggest that lipid rafts are critical for P2Y(2) receptor-mediated G(q/11)-PLC-Ca(2+) signaling and this cascade is important for cell migration in NG 108-15 cells.

A new ultrasonographic technique for diagnosing deep venous insufficiency--imaging and functional evaluation of venous valves by ultrasonography with improved resolution.

This is to demonstrate a new 2D-ultrasonographic technique which enabled clear resolution of deformed valves, visualization of venous reflux and quantitation of valve incompetence. In a 59-year-old Japanese female patient, ultrasonography was done using Aplio, Toshiba Medical Systems Co., Japan, equipped with 8 MHz linear probe capable of differential tissue harmonic imaging to diagnose the cause of her leg edema. Venous ultrasonography using this device at the popliteal venous valve in this patient demonstrated clear view of deformed venous valve and valve separation at one end of valvular agger while the other part of the valve is closed. Color Doppler failed to show venous reflux due to its low velocity. However, the appearance and disappearance of a thrombus-like echo could be imaged using 2D-ultrasonography. In addition, we were able to demonstrate the time-course change of valve opening and closing, and quantitate the valve incompetence using M-mode ultrasonography.

Peptidoglycan recognition protein (PGRP)-LE and PGRP-LC act synergistically in Drosophila immunity.

In innate immunity, pattern recognition molecules recognize cell wall components of microorganisms and activate subsequent immune responses, such as the induction of antimicrobial peptides and melanization in Drosophila. The diaminopimelic acid (DAP)-type peptidoglycan potently activates imd-dependent induction of antibacterial peptides. Peptidoglycan recognition protein (PGRP) family members act as pattern recognition molecules. PGRP-LC loss-of-function mutations affect the imd-dependent induction of antibacterial peptides and resistance to Gram-negative bacteria, whereas PGRP-LE binds to the DAP-type peptidoglycan, and a gain-of-function mutation induces constitutive activation of both the imd pathway and melanization. Here, we generated PGRP-LE null mutants and report that PGRP-LE functions synergistically with PGRP-LC in producing resistance to Escherichia coli and Bacillus megaterium infections, which have the DAP-type peptidoglycan. Consistent with this, PGRP-LE acts both upstream and in parallel with PGRP-LC in the imd pathway, and is required for infection-dependent activation of melanization in Drosophila. A role for PGRP-LE in the epithelial induction of antimicrobial peptides is also suggested.

[Diagnosis of vascular complications at the puncture site after cardiac catheterization].

OBJECTIVES: Cardiac catheterization is increasingly used for the diagnosis or treatment of coronary artery disease. Previous studies that revealed the incidence of complications such as arteriovenous fistula and pseudoaneurysm were based on retrospective analysis of cohorts referred to vascular surgery. This study was designed to determine the incidence of arteriovenous fistula and pseudoaneurysm after percutaneous transluminal angiography. METHODS: All 557 consecutive patients undergoing cardiac catheterization were examined by ultrasonography from March 1, 2001 to April 1, 2002, to investigate the occurrence of arteriovenous fistula and pseudoaneurysm at the puncture site. RESULTS: Pseudoaneurysm was found in 16 patients (2.9%), and arteriovenous fistula in 12 patients (2.2%). Pseudoaneurysm in 7 patients (43.8%) and arteriovenous fistula in 6 patients (50.0%) were diagnosed only by ultrasonic examination. There were more female patients (9 patients, 56.3%) than male with pseudoaneurysm (p < 0.01). The puncture site was located after the division of the deep femoral artery and superficial femoral artery in all patients with complications. CONCLUSIONS: Ultrasonic examination was useful for diagnosis of complications such as arteriovenous fistula and pseudoaneurysm after cardiac catheterization.

[Quadricuspid pulmonary valve with valvular stenosis and regurgitation identified by transthoracic echocardiography: a case report].

A 74-year-old man was admitted to our hospital complaining of dyspnea. Parasternal transthoracic echocardiography showed a quadricuspid pulmonary valve above the aortic valve and a hypoplastic accessory cusp between the right and left cusps of the pulmonary valve. The pulmonary valve ring diameter was normal (26 mm) but the transvalvular peak velocity was 3.5 m/sec, suggesting a pressure gradient of 49 mmHg across the pulmonary valve. The pulmonary valve had thickening and decrease in mobility of the leaflets without complete closure during diastole, and severe pulmonary regurgitation was present. Heart failure was treated successfully with digitalis and diuretics. Quadricuspid pulmonary valve is difficult to identify using transthoracic echocardiography because of the anatomical features. In this case, the dilated main pulmonary artery caused the pulmonary valve orifice to shift anteriorly, allowing visualization of the short-axis view of the pulmonary valve.