Intramolecular Exciton Coupling and Induced Circular Dichroism From Bilirubin-Ephedrine Heteroassociation Complexes. Stereochemical Models for Protein Binding

Bichromophoric (4Z,15Z)-bilirubin-IXa, the cytotoxic and yel-: low-orange pigment of jaundice, prefers to adopt either of two enantiomeric intramolecularly hydrogeri-bonded conformations that are in dynamic equilibrium in solution. In the presence of optically active amino-alcohols, particularly ephedrines, the pigment solutions exhibit intense bisignate circular dichroism in the region of the bilirubin long wavelength UV-visible absorption band. The most intense circular dichroism Cotton effects, I !\u27lE; i --+ 200, are induced by O-methylephedrines, exceeding even those generally exhibited by bilirubin complexes with serum albumin and other proteins. Like serum albumin and other proteins, the optically active amino alcohols act as chiral templates, inducing an asymmetric transformation of bilirubin, whose induced bisignate circular dichroism Cotton effect originate from exciton sphtting of its two component pyrromethenone chromophores. The amines are thought to serve as agents for chiral molecular recognitlon by forming .diastereorneric salts with the pigment. And the complementary action of fJ-aryl and proximal hydroxyl and methoxyl group s provides insight into the binding forces important in bilirubinprotein binding

Vibrational Circular Dichroism Detects Symmetry Breaking due to Conformational Mobility in C2-Symmetry Chiral Molecules and Provides Further Insight into Inter-Chromophoric Interactions

Bicyclo[3.3.1]nonane-2,6-dione (1) and bicyclo[3.3.1]nona-3,7-diene-2,6-dione (2) have been examined by vibrational circular dichroism (VCD), which, as for most C2-symmetric systems, exhibits strong VCD signals. In the case of 2, VCD signals are stronger and sharper with several bisignate doublets; for 1, signals are less intense and broader. The VCD and IR spectra are excellently predicted by DFT calculations: only one conformer is present for 2, while for 1, three main conformers, related through concerted skeleton torsional motions are present (two of them being interchanged by C2-rotation). The VCD spectrum shows specific features for the different conformers, such that correct population factors are crucial for reproducing experimental data. Also, the TD-DFT prediction of ECD (electronic circular dichroism) spectra is good. By comparing the spectroscopic signature of the two molecules (both VCD and ECD) and by careful analysis of the theoretical results, the role of the C=C double bond in compound (2) is evidenced. The double bond contributes toward enhancing the CD response both electronically and vibrationally

Downbeat Nystagmus in a 7-Year-Old Girl with Epstein-Barr Virus-Associated Meningitis and Cerebellitis

Downbeat nystagmus is a type of jerk nystagmus that may be seen in patients with lesions affecting the vestibulocerebellum. This is a case of a 7-year-old girl presenting with a history of fever, headache, and episodic vertigo with downbeat nystagmus. The diagnosis of Epstein-Barr virus meningitis with acute cerebellitis was made by contrast magnetic resonance imaging, cerebrospinal fluid analysis, and serum Epstein-Barr virus titers. Contrast magnetic resonance imaging demonstrated enhancement of the meninges and inferior cerebellar folia, correlating with the neuroophthalmological symptom of downbeat nystagmus

Insights into the Structures of Bilirubin and Biliverdin from Vibrational and Electronic Circular Dichroism: History and Perspectives

: In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds

Results of a randomized, double blind, placebo controlled, crossover trial of melatonin for treatment of Nocturia in adults with multiple sclerosis (MeNiMS)

© 2018 The Author(s). Background: Nocturia is a common urinary symptom of multiple sclerosis (MS) which can affect quality of life (QoL) adversely. Melatonin is a hormone known to regulate circadian rhythm and reduce smooth muscle activity such as in the bladder. There is limited evidence supporting use of melatonin to alleviate urinary frequency at night in the treatment of nocturia. The aim of this study was to evaluate the effect of melatonin on the mean number of nocturia episodes per night in patients with MS. Methods: A randomized, double blind, placebo controlled crossover trial was conducted. 34 patients with nocturia secondary to multiple sclerosis underwent a 4-day pre-treatment monitoring phase. The patients were randomized to receive either 2 mg per night (taken at bedtime) of capsulated sustained-release melatonin (Circadin®) or 1 placebo capsule for 6 weeks followed by a crossover to the other regimen for an additional 6 weeks after a 1-month washout period. Results: From the 26 patients who completed the study, there was no significant difference observed in the signs or symptoms of nocturia when taking 2 mg melatonin compared to placebo. The primary outcome measure, mean number of nocturia episodes on bladder diaries, was 1.8/night at baseline, and 1.4/night on melatonin, compared with 1.6 for placebo (Medians 1.70, 1.50, and 1.30 respectively, p = 0.85). There was also no significant difference seen in LUTS, QoL and sleep quality when taking melatonin. No significant safety concerns arose. Conclusions: This small study suggests that a low dose of melatonin taken at bedtime may be ineffective therapy for nocturia in MS. Trial registration: (EudraCT reference) 2012-00418321 registered: 25/01/13. ISRCTN Registry: ISRCTN38687869

Intramolecular Exciton Coupling and Induced Circular Dichroism From Bilirubin-Ephedrine Heteroassociation Complexes. Stereochemical Models for Protein Binding

Bichromophoric (4Z,15Z)-bilirubin-IXa, the cytotoxic and yel-: low-orange pigment of jaundice, prefers to adopt either of two enantiomeric intramolecularly hydrogeri-bonded conformations that are in dynamic equilibrium in solution. In the presence of optically active amino-alcohols, particularly ephedrines, the pigment solutions exhibit intense bisignate circular dichroism in the region of the bilirubin long wavelength UV-visible absorption band. The most intense circular dichroism Cotton effects, I !\u27lE; i --+ 200, are induced by O-methylephedrines, exceeding even those generally exhibited by bilirubin complexes with serum albumin and other proteins. Like serum albumin and other proteins, the optically active amino alcohols act as chiral templates, inducing an asymmetric transformation of bilirubin, whose induced bisignate circular dichroism Cotton effect originate from exciton sphtting of its two component pyrromethenone chromophores. The amines are thought to serve as agents for chiral molecular recognitlon by forming .diastereorneric salts with the pigment. And the complementary action of fJ-aryl and proximal hydroxyl and methoxyl group s provides insight into the binding forces important in bilirubinprotein binding