Selective inhibitory effect of new phosphodiesterase inhibitors on PDE isozymes in guinea pig cardiac muscle

Selective inhibition of seven new PDE inhibitors on cyclic nucleotide PDE isozymes was investigated. Three PDE isozymes (PDE I, II and III) of guinea pig left ventricular muscles were used. All tested agents inhibited cyclic AMP hydrolysis by PDE III in a concentration-dependent manner. Some agents represented more potent and selective inhibitory effect on PDE III than that of imazodan.     

Timolol induces HSV-1 ocular shedding in the latently infected rabbit

Timolol iontophoresis into the eye can induce herpes simplex virus type 1 (HSV-1) shedding in rabbits latently infected with HSV-1 strain McKrae. Anodal iontophoresis of 0.01% timolol was done at 0.8 mAmp for 8 min once a day for 3 consecutive days. Viral shedding was determined by the presence of HSV-1 in the preocular tear film obtained by eye swabs. In two experiments, iontophoresis of 0.01% timolol resulted in all eyes (18/18) shedding HSV-1 for an average duration of 4.3 days. When 5.0% timolol was applied topically to rabbit eyes supersensitized by iontophoresis of 6-hydroxydopamine (6-HD), all eyes (10/10) shed virus for an average duration of 2.9 days. All eyes (12/12) receiving iontophoresis of 6-HD, pre- and posttreatment with topical application of 5.0% timolol, and posttreatment with topical application of 1.0% epinephrine shed virus for an average duration of 3.6 days. Eyes treated with topical application of 5.0% timolol alone showed no difference in HSV-1 ocular shedding, compared with untreated eyes. We concluded that both iontophoresis of 0.01% timolol and topical application of 5.0% timolol to adrenergically supersensitized eyes induced HSV-1 shedding reliably and with a high frequency, and that topically applied timolol does not block the HSV-1 ocular shedding induced by epinephrine in adrenergically supersensitized eyes.     

Evaluation of the NucliSens EasyQ HIV-1 v1.1 and RealTime HIV-1 kits for quantitation of HIV-1 RNA in plasma

Human immunodeficiency virus type-1 (HIV-1) RNA viral load is an important biomarker to evaluate the therapeutic efficacy of antiretroviral drugs and to monitor disease progression in HIV-infected individuals. We compared HIV-1 RNA quantitation between two different kits, the NucliSens EasyQ^® HIV-1 v1.1 (EasyQ, bioMérieux) and RealTime HIV-1 (RealTime, Abbott), using HIV-1 RNA quality control (QC) materials, cell-cultivated viruses, and the plasma samples of 104 patients with HIV. Correlation between the two kits for HIV RNA-1 quantitation with clinical samples was high (R = 0.91). Based on results obtained with quality control standards, the reproducibility of the RealTime kit was higher than the EasyQ kit: the viral load value and coefficient of variation of each kit was 4.11 ± 0.136 and 3.3% for EasyQ and 3.55 ± 0.042 and 1.2% for RealTime, respectively (P < 0.002).This is the first comparative analysis of the detection limit and reproducibility of two different quantitation kits using clinical plasma samples from Korean HIV-1-infected patients. It will serve a useful reference to determine correction values for each HIV-1 RNA quantitation kits and to choose an appropriate assay kit for each laboratory.     

<Emphasis Type="Italic">In situ</Emphasis> and <Emphasis Type="Italic">ex vivo</Emphasis> evaluation of a wireless magnetoelastic biliary stent monitoring system

This paper presents the in situ and ex vivo evaluation of a system that wirelessly monitors the accumulation of intimal tissue and sludge in a biliary stent. The sensing element, located within the stent, is a magnetoelastic resonator that is queried by a wireless radio frequency signal. The in situ testing uses a commercially-available self-expanding biliary stent enhanced with a 1 mm × 25 mm magnetoelastic ribbon sensor (formed from Metglas™ 2605SA1). The stent has a conformal magnetic layer (consisting of strontium ferrite particles suspended in polydimethylsiloxane) that biases the sensor. The external interrogation module is able to acquire a signal from the sensor from a distance of at least 5 cm while the sensor is implanted in a porcine carcass and loaded with biological fluids. The ex vivo testing uses bile harvested from the porcine carcass. The response of a 1 mm × 25 mm magnetoelastic ribbon sensor is first calibrated with fluids of known density and viscosity, and the calibrated sensor is used to estimate that the viscosity of the harvested bile is 2.7–3.7 cP. The test results presented in this paper illustrate the fundamental usability of the system when the sensor is implanted, loaded by biological fluids, and interrogated in a surgical setup.     

Predictors of Remission and Relapse of Diabetes after Conventional Gastrectomy for Gastric Cancer: Nationwide Population-Based Cohort Study

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Engineering and Visualization of Bacteria for Targeting Infarcted Myocardium

Optimization of the specific affinity of cardiac delivery vector could significantly improve the efficiency of gene/protein delivery, yet no cardiac vectors to date have sufficient target specificity for myocardial infarction (MI). In this study, we explored bacterial tropism for infarcted myocardium based on our previous observations that certain bacteria are capable of targeting the hypoxic regions in solid tumors. Out of several Escherichia coli or Salmonella typhimurium strains, the S. typhimurium defective in the synthesis of ppGpp (ΔppGpp S. typhimurium) revealed accumulation and selective proliferation in the infarcted myocardium without spillover to noncardiac tissue. The Salmonellae that were engineered to express a variant of Renilla luciferase gene (RLuc8), under the control of the E. coli arabinose operon promoter (P_BAD), selectively targeted and delivered RLuc8 in the infarcted myocardium only upon injection of -arabinose. An examination of the infarct size before and after infection, and estimations of C-reactive protein (CRP) and procalcitonin indicated that intravenous injection of ΔppGpp S. typhimurium did not induce serious local or systemic immune reactions. This current proof-of-principle study demonstrates for the first time the capacity of Salmonellae to target infarcted myocardium and to serve as a vehicle for the selective delivery of therapeutic agents in MI.