Isomerization of all-trans β-carotene and canthaxanthin embedded in solid MCM-41 and Ti−MCM-41 occurs during photoirradiation. The isomerization proceeds with high efficiency, primarily via the ...carotenoid radical cation (Car•+). The intermediacy of Car•+ was confirmed by studies of the isomerization caused by oxidation of these two compounds in Fe−MCM-41. Strong selective formation of the 13-cis isomer occurs for all-trans β-carotene, but no such selectivity was found for canthaxanthin. These phenomena are attributed to different orientations of the two compounds in these hosts. Molecular mechanics calculations show that formation of the 13-cis isomer of β-carotene is more favorable than that of other cis isomers in the MCM-41 host.
Introduction
Trimetazidine (TMZ) was shown to reduce angina symptoms and increase the exercise capacity in stable angina (SA) patients. A new formulation allowing a once-daily (od) dosage could ...improve patients’ satisfaction and adherence.
Methods
ODA was a 3-month, observational, multicenter, prospective Russian study in SA patients with persistent symptoms despite therapy. Angina attack frequency, short-acting nitrate (SAN) consumption, adherence to antianginal medications, and overall efficacy and tolerability of TMZ 80 mg od were assessed in a real-world setting.
Results
A total of 3066 patients were included (mean age 62.8, 48% male). After 3 months, TMZ 80 mg od treatment led to a significant (
p
< 0.001) decrease in angina attack frequency (from 4.7 ± 3.5 to 0.9 ± 1.3/week) and SAN use (from 4.5 ± 3.9 to 0.7 ± 1.3/week). Overall tolerability and effectiveness were rated as “very good” by the majority of physicians. Medication adherence improved significantly, with good adherence reported by 56% of patients (vs. 24% at baseline,
p
< 0.0001) and non-adherence by 3% (vs. 36% at baseline,
p
< 0.0001) at month 3. Patient satisfaction with TMZ od was 9.5 on a scale of 1 to 10 (very satisfied). Patients reported improved physical activity: more patients reported no limitations (15% vs. 1% at baseline
p
< 0.01), slight limitation (46% vs. 5% at baseline,
p
< 0.001) or moderate limitation (30% vs. 23%,
p
< 0.01) and fewer patients reported substantial limitation (8% vs. 52% at baseline,
p
< 0.001) or very marked reduction (1% vs. 19% at baseline,
p
< 0.01) at month 3.
Conclusion
In this prospective, observational study, TMZ 80 mg od effectively reduced angina attacks and SAN consumption, improved physical activity and adherence and was well tolerated in chronic SA patients.
Trial Registration
ISRCTN registry Identifier, ISRCTN97780949.
Funding
Servier.
Plain Language Summary
Plain language summary available for this article.
Determine etiologic significance of clinical strains of E. coli O145:H28 isolated from feces of a patient with hemolytic-uremic syndrome (HUS).
20 E. coli strains isolated from feces of a patient ...with HUS that developed after an acute intestine infection were studied. Antigenic structure of strains was determined by sequencing of rib and fliC genes; presence of virulence genes (pap, aaf, sfa, afa, eaeA, bfpA, ial, hly, cnf, stx1, stx2, LT, ST and aer)--in PCR; ESBL production --by double disk method, ESBL genes--in PCR.
The strains contained rfb gene coding O145, fliC gene coding H7. Genes coding synthesis of stx2-toxin and intimin (eaeA) were detected. The strains were resistant to beta-lactams due to production of CTX-M class ESBL.
A causative agent E. coli O145:H28 was isolated from a patient with HUS that produces stx2-toxin and CTX-M class ESBL and has not been previously registered in Russian Federation.
Carotenoids (Car), β-Carotene (I), 8‘-apo-β-caroten-8‘-al (II), and canthaxanthin (III), incorporated into activated Cu−MCM-41 were examined by UV/vis and EPR spectroscopies. A Cu2+−Car complex was ...formed for I and III but not for II. Formation of a complex results in distortion of the all-trans carotenoid geometry and a tetragonal geometry for Cu2+. The binding energies of Car and Cu2+, the changes in the maximum absorption, and the bond lengths of Car after the formation of the Cu2+−Car complex were examined by semiempirical ZINDO/1 and ZINDO/S calculations. Formation of a complex between Car and Cu2+ favors both forward and back electron transfer (ET) reactions due to the short distance (∼2 Å) between Car and Cu2+, and reversible ET appears upon temperature cycling.
We studied the effects of intranasal administration of oligomeric forms of the α-synuclein protein, which plays an important role in the pathogenesis in a group of chronic neurodegenerative diseases, ...that is, synucleinopathies. Neurogenesis in the hippocampus, the number of dopaminergic neurons in the substantia nigra, locomotor and orienting-exploratory activity, learning and memory, and the emotional state were studied in aged animals. Twelve-month-old male C57Bl/6 mice were used for the experiments. The solution of oligomers of α-synuclein was administered daily to mice for 14 days. The behavioral testing included the open-field test, novel-object recognition, passive avoidance conditioning, and the elevated plus-maze. Proliferating cells, immature neurons, and dopaminergic neurons were detected using immunohistochemical staining with antibodies to the bromodeoxyuridine, doublecortin, and tyrosine hydroxylase markers. We found that α-synuclein oligomers induced a significant increase in the number of proliferating cells and immature neurons in the hippocampal dentate gyrus and a decrease in the number of dopaminergic neurons in the substantia nigra pars compacta. The treated mice exhibited decreased locomotor and orienting-exploratory activities, impaired formation and retrieval of episodic memory, and increased anxiety. Our data show that the non-motor behavioral effects of α-synuclein oligomers may be related to impairments in hippocampal neurogenesis and may be considered as experimental evidence of the involvement of postnatal neurogenesis in the development of synucleinopathies.
The 95−670 GHz EPR measurements at 5 K were performed on canthaxanthin radical cation chemically generated on silica−alumina. The 327 GHz and higher frequency EPR spectra were resolved into two ...principal components of the g tensor. Spectral simulation indicated this to be the result of g anisotropy where g ∥ = 2.0032 and g ⊥ = 2.0023. This type of g tensor is consistent with the theory for polyacene π-radical cations, which states that the g tensor becomes cylindrically symmetric with increasing chain length. This also demonstrates that the symmetrical unresolved EPR line at 9 GHz is due to a carotenoid π-radical cation with electron density distributed throughout the whole chain as predicted by RHF−INDO/SP molecular orbital calculations. The lack of temperature dependence of the EPR line widths over the range of 5−80 K at 327 GHz suggests rapid rotation of methyl groups even at 5 K that averages out the proton couplings from three oriented β-protons. In fact, similar line widths at 5 K were observed at 670 GHz. Simulation of EPR spectra at 95−250 GHz gives only symmetrical unresolved lines. The present work shows that the 327−670 GHz EPR measurements are sufficient to resolve the individual g tensors of C−H containing π-radicals in powder and frozen glasses. Symmetry differences can be deduced from which radical identification can be made.
The peroxyl radical location in horse heart myoglobin (Mb) oxidized with H2O2 was examined by 9−287 GHz electron paramagnetic resonance (EPR) spectroscopy along with the radicals formed upon ...oxidation of tyrosine (Tyr), tryptophan (Trp), and histidine (His) individual amino acids. X-ray crystallography of the horse heart Mb has revealed that Tyr103, Tyr146, Trp14, and His64 residues are in the vicinity of the Mb heme group and thus could be implicated in Mb oxidation. The 9 GHz axial EPR signal of the Mb peroxyl radical (g ∥ = 2.040 ± 0.003 and g ⊥ = 2.001 ± 0.001) is nearly identical with those of the radicals produced by irradiation of the individual amino acids in the presence of H2O2 (77 K). The 95−287 GHz measurements were sufficient to resolve the individual g tensor components of the Mb, Tyr, Trp, and His peroxyl radicals which cannot be distinguished at 9−35 GHz. The high-field EPR spectra of the Mb peroxyl radical were simulated using a Hamiltonian that describes the exchange and dipolar interaction between an oxoferryl iron and a protein radical. The exchange-coupled oxoferryl−protein radical pair could be best fitted with g values of g X = 2.0356, g Y = 2.0083, and g Z = 2.0024 for the radical, a dipolar coupling corresponding to a distance of 8.3 Å between the radical and the oxoferryl iron, and an exchange coupling (J) of 0.476 GHz. The determined g tensor and the distance related to the Tyr residue at position 146. Tyr146 is assumed to be the most likely candidate for the peroxyl radical location in oxidized Mb.
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