Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

<p>Abstract</p> <p>Background</p> <p>Phosphorothioated oligonucleotides (PS-ONs) have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs) and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV) infections in vitro and in vivo was therefore investigated.</p> <p>Results</p> <p>In vitro, a 40 mer degenerate AP (REP 9) inhibited both murine CMV (MCMV) and guinea pig CMV (GPCMV) with an IC₅₀of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C) inhibited MCMV with an IC₅₀of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs) was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism <it>in vivo</it>. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers.</p> <p>Conclusion</p> <p>These studies indicate that APs exhibit potent, well tolerated antiviral activity against CMV infection in vivo and represent a new class of broad spectrum anti-herpetic agents.</p

Inhibition of Bacterial Adherence on the Surface of Stents and Bacterial Growth in Bile by Bismuth Dimercaprol

Bacterial infection and biofilm formation on the surface of biliary stents is believed to be one of the main factors in stent occlusion. This study explored the role of the new reagent, bismuth dimercaprol, in preventing bacterial adherence and bacterial biofilm formation on the surface of biliary stents. Sterile porcine bile preparations, infected separately with Escherichia coli, Klebsiella pneumoniae, Enterobacter , and Enterococcus , were used as the perfusion media in an in vitro perfusion system. The bacterial growth in the media and the bacterial adherence on the surface of stents were tested when different concentrations of bismuth dimercaprol were used in the perfusion media. BisBAL (5 μ M ) did not inhibit the growth of any of the tested bacterial species. It did, however, significantly decrease the amount of bacteria adhering to the surface of stents for all bacterial strains except Escherichia coli . Bismuth dimercaprol (20 μ M ) significantly inhibited the growth of Escherichia coli, Klebsiella pneumoniae , and Enterobacter and, thereby, significantly decreased the amount of these bacteria adhering to the surface of stents. The unique bactericidal and anitbiofilm activities of bismuth thiols might contribute to delaying the process of biliary stent occlusion if the effective concentrations of bismuth thiols could be delivered to the target sites. The feasibility of this application of bismuth thiols deserves further investigation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44439/1/10620_2005_Article_2702.pd

Comparison of the sonographic features of the abdominal wall muscles and connective tissues in individuals with and without lumbopelvic pain.

Study Design: Cross sectional, case-control study.Objectives: Measure and compare the resting thickness of the four abdominal wall muscles, their associated perimuscular connective tissue (PMCT), and inter-recti distance (IRD) in persons with and without lumbopelvic pain (LPP), using ultrasound imaging (USI).Background: The muscles and PMCT of the abdominal wall assist in controlling the spine and functional deficits have been detected in LPP populations. Investigations of the abdominal wall in LPP are primarily concerned with muscle, most commonly the transversus abdominis (TrA) and internal oblique (IO). As the abdominal wall functions as a unit, it seems prudent that all 4 abdominal muscles and their associated connective tissues are considered concurrently.Methods: B-mode USI was used to measure the resting thickness of the rectus abdominis (RA), external oblique (EO), IO, and TrA muscles, the PMCT planes, and IRD in 50 male and female subjects (25 with and 25 without LPP; mean +/- SD age 36.3 +/- 9.4 and 46.6 +/- 8.0 years, respectively). Univariate correlation analysis was used to identify covariates. Analyses of covariance and Kruskal-Wallis test (IRD) were used to compare cohorts (alpha=0.05).Results: The LPP cohort had less total abdominal muscle thickness (LPP 18.9 +/- 3.0 mm, Control 20.3 +/- 3.0 mm; ANCOVA adjusted for body mass index [BMI], P=.03), thicker PMCT (LPP 5.5 +/- 0.2 mm, Control 4.3 +/- 0.2 mm; ANCOVA adjusted for BMI, P=.007), and wider IRD (LPP 11.5 +/- 2.0 mm, Control 8.4 +/- 1.8 mm; Kruskal-Wallis, P=.005). Analysis of individual muscle thickness revealed no difference in the EO, IO, and TrA, but a thinner RA (LPP 7.8 +/- 1.5 mm, Control 9.1 +/- 1.2 mm; 56 ANCOVA adjusted for BMI, P&lt;.001) in the LPP cohort.Conclusions: To our knowledge this is the first study to investigate the morphological characteristics of all 4 abdominal muscles and PMCT in individuals with LPP. The results suggest altered loading of the PMCT and linea alba, which may be secondary to an altered motor control strategy that involves a reduced contribution of the RA. Further, the change in RA and connective tissue morphology may be more evident than changes in EO, IO, and TrA thickness in persons with LPP. The causes and functional implications of these changes warrant further investigation, as does the role of the RA muscle in the development and persistence of LPP.<br/