Multimodal imaging in photic retinopathy

Letter to the Editor     

Simulation of 125I-based radioprobing experiments to study DNA quadruplex structure and topology

Purpose: Certain guanine-rich DNA sequences have the capacity to fold into four-stranded structures stabilized by the stacking of square planar arrangements of four hydrogen-bonded guanine bases. However both the overall topology of folding and the more detailed three dimensional structure of these quadruplexes is difficult to determine or predict, and they can be polymorphic, altering radically depending on environmental conditions. Radioprobing experiments, in which Auger electrons emitted during the decay of a ¹²⁵I-containing base induce strand cleavage in a distance- and structure-dependent manner, have provided possible means of determining these details. Here we have used a combination of computer simulation methods to study the information obtained by one such experiment, reported in 2004.

Method: Models were constructed of three quadruplex topologies considered in the experiment, and one other topology proposed more recently. Molecular Dynamics simulations were used to equilibrate these structures and monitor how they evolved over several nanoseconds in solution. Snapshots from the trajectories were then subjected to Monte Carlo track structure prediction, from which theoretical cleavage patterns have been extracted.

Results: The four topologies were found to yield quite different cleavage patterns, which allow the presence of particular conformations in an experiment to be predicted.

Conclusion: Radioprobing, which is usable in biologically relevant environments, is sensitive enough to distinguish with some confidence between alternative folding topologies in a DNA structure. Monte Carlo track structure simulation can reinforce or question conclusions drawn from experiment, and Molecular Dynamics used with various restraints provides a practical means of guiding a model towards one that yields cleavage patterns closer to those found experimentally.     

Esophageal Aperistalsis and Gastroesophageal Reflux Disorder: Return of Peristalsis after H2-Blocker Therapy

Objectives: Distal esophageal aperistalsis has rarely been reported among patients with gastroesophageal reflux disorder. The purpose of this study, therefore, was to address the frequency with which disorders of peristalsis in general-and distal esophageal aperistalsis in particular-occur in adults with gastroesophageal reflux disorder. Patients and Methods: We studied 314 patients who were referred to our gastrointestinal motility laboratory. On the basis of the endoscopic data, they were divided into three groups: group I, symptomatic patients without endoscopic esophagitis; group II, patients with mild endoscopic esophagitis; and group III. patients with erosive esophagitis. An age-matched group of patients with chest pain unrelated to reflux served as the control. Results: Some form of peristaltic dysfunction was recorded in 56% of the patients with gastroesophageal reflux disorder, significantly more than in the control group ( p < 0.01). A significant correlation existed between the esophageal motor dysfunction scores and the severity of reflux disease. Distal esophageal aperistalsis was present in 3.1% of the reflux groups. There was a correlation between severity of reflux disease and the prevalence of aperistalsis. Aperistalsis occurred in none of the patients in group I, in 3.6% of group II, and in 12.5% of group III ( p < 0.0001). Seven of the patients with aperistalsis who has been treated with H2-blockers were reexamined 4 months later. Return of peristalsis was seen in three of them. Conclusion: Esophageal aperistalsis can be seen in a minority of patients with severe gastroesophageal reflux disorder and is probably a reversible condition.     

Future directions of laser phototherapy for diagnosis and treatment of malignancies: Fantasy,fallacy, or reality?

A new and highly promising adjunctive modality for the diagnosis and therapy of malignancies is under development using lasers and tumor targeting dyes. To reach the eventual goal of clinical treatment, several current “fantasies and fallacies” regarding laser applications in medicine must be identified and their problems clearly outlined. A multidisciplinary scientific approach is also required to enable the clinical practicality of this laser targeting approach. Many new dyes and laser wavelengths are being tested to improve specific tumor uptake and/or retention, lower systemic toxicity, increase tissue penetration, and identify fluorochromes with synergistic properties to further enhance laser tumoricidal effects. Rapid technological advancements in magnetic resonance imaging may now provide an extremely sensitive way to detect and monitor laser-tissue effects, and allow efficient interstitial laser phototherapy of deep and sometimes inaccessible tumors. The current and future prospectives of the emerging field of laser phototherapy are described.     

Effects of nitric oxide on gentamicin toxicity in isolated perfused rat kidneys

BACKGROUND: There have been many studies in recent years concerning the role of nitric oxide (NO) in acute renal failure (ARF). In this study, the effects of the inhibition or the induction of NO synthase (NOS) on gentamicin-induced ARF was investigated in isolated perfused rat kidneys. METHODS: Kidneys from male Sprague-Dawley rats were perfused in situ for 90 min. Perfusion was conducted in the presence of inulin (60 mg/dL in perfusion buffer) as a glomerular filtration rate (GFR) marker. Six groups (total: 42 rats) were studied: group 1, controls with no treatment; group 2, L-arginine (2 mM in perfusate); group 3, L-nitro-arginine-methyl ester (L-NAME, 0.1 mM in perfusate); group 4, gentamicin (GM, 0.5 mg/mL in perfusate); group 5, GM + L-arginine (same dose as groups 2 and 4) and; group 6, GM + L-NAME (same dose as groups 3 and 4). Cell injury was assessed by measuring N-acetyl-beta-D-glucosaminidase (NAG), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) activity in urine. RESULTS: L-arginine prevented, whereas L-NAME enhanced, GM-induced enzyme release and GFR reduction. Histological studies showed that GM-treated kidneys had clear signs of tubular damage and this damage was increased by simultaneous L-NAME and GM administration. CONCLUSION: This study suggests that NO formation could prevent the GM-induced nephrotoxicity in this ARF model.