A reversible monoamine oxidase inhibitor, toloxatone: Structural and electronic properties

Toloxatone is a reversible MAO_A-inhibitor, marketed as antidepressant (Humoryl^®), with an original chemical structure. It differs from first generation irreversible MAOIs, known to induce covalent bonds with the enzyme active site. In order to understand the mechanism of the reversible inactivation of the MAO, as a first step, a detailed structural and electronic analysis was undertaken. An X-ray diffraction-crystallographic study showed that toloxatone is a planar molecule and brought to light hydrogen bonds and π-π interactions. MO calculations confirmed the planar structure as energetically favoured. Electronic analysis demonstrated a delocalization of both ring systems. The combined results give evidence for the potential of toloxatone to participate in reversible, long distance interactions with an appropriate partner.     

Ocular MR imaging and spectroscopy: an ex vivo study

Six eyes, freshly enucleated because of choroidal melanoma, were imaged on a 1.4-T superconducting magnetic resonance (MR) imaging system, and relaxation times were calculated for various parts of the eye. Unfixed fresh tissue samples were obtained for nuclear magnetic resonance spectroscopy (NMRS) on a variable-field (0.19-1.4 T) resistive unit. Detailed ocular anatomy was demonstrated. The NMRS relaxation times correlated with the MR imaging intensity patterns. The sensitivity of MR imaging to states of hydration provides an excellent window for appreciation of ocular anatomy.     

MM6 Decision Analysis: What is its Utility for Pharmacoeconomic Analysis?

This session is intended for sharing and comparing computer software applications for research, management, and practice. Software applications will be demonstrated for decision analysis, cost effectiveness analysis, multiattribute utility computation, and assessing patient utilities. Desktop applications, will be discussed. Laptop and handheld computer software will be demonstrated. Pharmacoeconomic software allows data to be analyzed from different perspectives: patient, provider, hospital, managed care, and society. Software models also allow assessment of health care products or services from different quantitative perspectives: cost of illness, cost minimization, cost-benefit, cost-effectiveness, and cost-utility. The integration of decision analysis and spreadsheets will also be discussed. Software is utilized to collect information, analyze data, present findings, or educate managers, providers and patients. Pros and cons of each analytical and software approach will be discussed. Participants are encouraged to bring their own laptops to demonstrate their own software or related Internet offerings in an informal roundtable fashion. Software beta versions allowed; "viruses" discouraged.     

A double‐blind,randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo

Background Among all the topical immunomodulators, vitiligo's mainstay therapy includes topical corticosteroids. Many other non‐immune theories have also been suggested for vitiligo's pathogenesis, but the role of oxidative stress has gained more importance in recent years. Objective To compare the effect of topical 0.05% betamethasone vs. catalase/dismutase superoxide (C/DSO). Study design Randomized, matched‐paired, double‐blind trial. Setting Dermatology Section, University of Antioquia, Medellín, Colombia. Subjects Patients (aged > 18 years or between 12 and 18 years) with parent's informed consent, with stable or active bilateral vitiligo. Intervention Topical 0.05% betamethasone or C/DSO. Methods Two lesions similar to each other in size were chosen. All assessments were made by two blinded investigators, and photographs were subjected to morphometry analysis. Main outcome Skin repigmentation by digital morphometry. Results Twenty‐five patients were enrolled in the study (21 women and 4 men). Mean age of participants was 40 years (range: 12–74 years). One patient on C/DSO experienced a mild local erythematous papular rash that self‐resolved. At 4 months of therapy, there was no statistical difference on the percentage of repigmentation between betamethasone and C/DSO (5.63% ± 27.9 vs. 3.22% ± 25.8, respectively, P = 0.758). After 10 months of therapy, the percentage of skin repigmentation increased to 18.5 ± 93.14% with betamethasone and to 12.4 ± 59% with C/DSO, but again, we found no statistical differences (P = 0.79). Discussion and conclusions Few studies have described objective methods to evaluate repigmentation among vitiligo patients. Digital morphometry provides an objective assessment of repigmentation in vitiligo. Objective vitiligo repigmentation with topical C/DSO at 10 months is similar to topical 0.05% betamethasone. Although a mild adverse effect was related to the use of C/DSO, such finding was not severe enough to discontinue treatment.     

Meniscus tears of the knee: prospective evaluation with CT

A total of 209 patients underwent prospective axial computed tomography (CT) examinations of the knee to evaluate the ability of this technique to identify and characterize knee menisci in patients believed to have meniscus tears. Of the 359 knees examined, 105 subsequently underwent arthrography, arthroscopy, or arthrography and arthroscopic surgery. In this group, the sensitivity of CT was 88.5%, specificity was 95.5%, and accuracy was 91.5%. Although axial CT is a sensitive and effective method for the detection and characterization of tears involving the medial and lateral menisci, purely horizontal or nondisplaced peripheral tears may be difficult to demonstrate.     

An anti-EnaTS detected in the serum of an MiI homozygote

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.