10 research outputs found
Complexation of halide ions to tyrosine: role of non-covalent interactions evidenced by IRMPD spectroscopy
The binding motifs in the halide adducts with tyrosine ([Tyr + X]-, X = Cl, Br, I) have been investigated
and compared with the analogues with 3-nitrotyrosine (nitroTyr), a biomarker of protein nitration, in a
solvent-free environment by mass-selected infrared multiple photon dissociation (IRMPD) spectroscopy
over two IR frequency ranges, namely 950â1950 and 2800â3700 cm-1. Extensive quantum chemical
calculations at B3LYP, B3LYP-D3 and MP2 levels of theory have been performed using the 6-311++G(d,p)
basis set to determine the geometry, relative energy and vibrational properties of likely isomers and
interpret the measured spectra. A diagnostic carbonyl stretching band at B1720 cm-1 from the intact
carboxylic group characterizes the IRMPD spectra of both [Tyr + X]- and [nitroTyr + X]-, revealing that
the canonical isomers (maintaining intact amino and carboxylic functions) are the prevalent structures.
The spectroscopic evidence reveals the presence of multiple non-covalent forms. The halide complexes
of tyrosine conform to a mixture of plane and phenol isomers. The contribution of phenol-bound
isomers is sensitive to anion size, increasing from chloride to iodide, consistent with the decreasing
basicity of the halide, with relative amounts depending on the relative energies of the respective
structures. The stability of the most favorable phenol isomer with respect to the reference plane
geometry is in fact 1.3, -2.1, -6.8 kJ mol-1, for X = Cl, Br, I, respectively. The change in p-acidity by ring
nitration also stabilizes anionâp interactions yielding ring isomers for [nitroTyr + X]-, where the anion is
placed above the face of the aromatic ring
Oxidative Stress in Cancer-Prone Genetic Diseases in Pediatric Age: The Role of Mitochondrial Dysfunction
Oxidative stress is a distinctive sign in several genetic disorders characterized by cancer predisposition, such as Ataxia-Telangiectasia, Fanconi Anemia, Down syndrome, progeroid syndromes, Beckwith-Wiedemann syndrome, and Costello syndrome. Recent literature unveiled new molecular mechanisms linking oxidative stress to the pathogenesis of these conditions, with particular regard to mitochondrial dysfunction. Since mitochondria are one of the major sites of ROS production as well as one of the major targets of their action, this dysfunction is thought to be the cause of the prooxidant status. Deeper insight of the pathogenesis of the syndromes raises the possibility to identify new possible therapeutic targets. In particular, the use of mitochondrial-targeted agents seems to be an appropriate clinical strategy in order to improve the quality of life and the life span of the patients
Empiric antibiotics therapy for mildly elevated prostate specific antigen: Helpful to avoid unnecessary biopsies?
Purpose: The management of mildly elevated (4.0-10.0 ng/ml) prostate specific antigen (PSA) is uncertain. Immediate prostate biopsy, antibiotic treatment, or monitoring PSA level for 1-3 months is still in controversy. Materials and Methods: We retrospectively analysed the effect of empiric antibiotics on an increased PSA in a mono-institutional study. We analysed the data of 100 patients with a PSA of 4-10 ng/ml and normal digital rectal examination undergoing their first prostate biopsy. Patients were divided in two different cohorts. One cohort was submitted to antibiotic therapy (Levoxacin 500 mg daily for 20 days) and both cohort had a re-dosing of PSA before the prostate biopsy. Results: Average age of the whole group of patients was 66.48 ± 8.32 years and their average initial PSA level was 6.67 ± 1.57 ng/mL. In the treated group (N = 49) 29 patients had a decreasing PSA value from mean baseline PSA value of 6.6 ± 1.54 ng/ml to the re-dosed mean PSA level of 5.4 ± 1,61 ng/ml (p = 0.7); 20 patients didnât experience a decrease PSA value, with a mean PSA level of 6.9 ± 1.68 ng/ml. In the control group (N = 51), 30 patients had a decrease of PSA level from mean baseline PSA level of 6.5 ± 1,59 ng/ml to a re-dosed PSA level of 5.5 ± 1.57 ng/ml; 21 patients didnât experience a decrease of PSA value, with a mean PSA level of 6.7 ± 1.71 ng/ml. Multivariate analysis of age, PSA changes, antibiotics therapy and biopsy results (presence or absence of cancer) revealed no significant difference between the two cohorts. Sepsis after biopsy occurred in 3 patient in the antibiotics group (6%) and in one of the control group (2%). Conclusions: The study, even with some limitations, does not seem to show an advantage due to the administration of antibacterial therapy to reduce PSA values before prostate biopsy and subsequently to reduce unnecessary prostate biopsies
Vibrational Signatures of S-Nitroso Glutathione as Gaseous, Protonated Species
International audienceThe gas-phase ions of protonated L-glutathione as native species, [GSH+H]+, and S-nitroso derivative, [GSNO+H]+, have been generated by electrospray ionization and probed via infrared multiple photon dissociation (IRMPD) action spectroscopy. Insight into the conformational landscape is gained from the interpretation of the IR spectra aided by high-level theoretical calculations, which enables a structural assignment disclosing both the site of protonation and the intramolecular hydrogen bond network. Calculations yield the low-energy structures of [GSNO+H]+. A admixture of the four most stable ones (SN1, AN1, SN2 and AN2) is apt to account for the experimental IRMPD spectra obtained in both the 1000-2000 cm-1 and the 3100-3700 cm-1 spectral ranges. The most stable form of [GSNO+H]+, SN1, protonated at the amino group, presents a syn conformation at the S-N (partial) double bond and all peptidic carbonyls involved in (strong) C=O...H-N hydrogen bonds, so allowing the closure of a C5 (ÎČ-strand), two C7 (Îł-turn) and one C9 membered rings. An appreciable barrier to rotation of 43 kJ mol-1 about the S-N bond is found to separate SN1 from the analogous anti isomer AN1, which lies only 0.70 kJ mol-1 higher in free energy. Conformers obtained for [GSH+H]+ are very similar to the [GSNO+H]+ counterparts, indicating that the S-nitrosation motif does not affect significantly the geometry of the peptide. The observed Îœ(NO) signatures at 1622 and 1690 cmâ1, merged with other absorptions, are revealed by their sensitivity to 15NO isotope labeling, and by comparison with the IRMPD spectrum of native [GSH+H]+, providing a diagnostic probe for the S-nitrosation feature in natural peptides
Protonated hexaazamacrocycles as selective K+ receptors
Protonated hexaazamacrocycle [MâąH]+ is able to detect K+ ions present at
ppb level in methanolic solutions containing 10â5 M of Na+ ions. The high sensitivity
and selectivity of [MâąH]+ for K+ is ascribed to the favorable energy balance between
the K+ ion desolvation and its coordination to the [MâąH]+macrocycle, which allows the
formation of the corresponding adduct before the Coulombic explosion of the ESI-MS
nanodroplets
One-Electron Oxidation of Methionine-Containing Dipeptides of Reverse Sequence: Sulfur versus Sulfoxide Characterized by IRMPD Spectroscopy and Static and Dynamics DFT Simulations
Gas-phase
structural modifications induced by the oxidation of
methionine of the two peptides of reverse sequence, methionineâvaline
(<b>Met-Val</b>) and valineâmethionine (<b>Val-Met</b>), have been studied by mass-selected IR multiple photon dissociation
(IRMPD) spectroscopy in the 800â2000 cm<sup>â1</sup> fingerprint range at the Centre Laser Infrarouge dâOrsay
free-electron laser facility. The oxidation has been achieved by <sup>âą</sup>OH radicals generated by Îł radiolysis. IRMPD
spectra were interpreted by static and harmonic DFT calculations and
BornâOppenheimer molecular dynamics simulations, which are
employed to take into account all anharmonic and finite-temperature
effects. The diagnostic signature of the sulfoxide group in the final
products of <b>Met-Val</b> and <b>Val-Met</b> oxidations,
which is missing in the spectra of native peptides, has been recorded.
Evidence has also been gathered that a mixture of R and S isomers
of close energies is formed. An interconversion between different
isomers has been unveiled in the case of the oxidized <b>Met-Val</b> dipeptide
Observational database serenoa repens (DOSSER): Overview analysis and results - A multicentric SIUrO (Italian Society of Oncological Urology) Project
Objective: Men affected with Benign Prostate Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) are demonstrating to require an increasing amount of attention from Urologists and Primary-care Physicians. Over the years, common urological medications were based on either \u3b1-blockers and/or 5\u3b1-reductase inhibitors.During the last decade the phytotherapeutic drugs are gaining a more often central role in the BPH and LUTS managements. In particular, clinical usage of the extract of the dried ripe fruit of serenoa repens with a dosage of 320 mg per day, has shown its clinical efficacy and its superiority. Purpose of this multicentric observational retrospective study was to evaluate all the urological aspects (clinical, biochemical, instrumental and pathological) of patients affected by BPH and LUTS, with a PSA < 10 ng/ml, a previous negative prostatic biopsy and in therapy with a daily dose of 320/640 mg of serenoa repens.
Patients and Methods: The study was conducted in 8 different centers throughout Italy from September 2010 to November 2011. Data and information of 298 men with an average of 63 years (mean PSA of 5.4 ng/ml and mean prostate gland volume of 57 cc), affected by non-acute urinary symptoms caused by BPH, a dosed PSA level inferior to 10 ng/ml, a previous negative prostate biopsy and in therapy with serenoa repens alone or associated to an \u3b1-blocker, were retrospectively inserted in an extensive on-line SIUrO Database. Comprehensive questionnaires were filled in for each patient at 3 and 6 months of follow-up. Each questionnaire contained various sections, each of them composed by several items: dosed PSA levels, uroflowmetry, International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5), trans-rectal ultrasound (TRUS) patterns, digital rectal examinations (DRE) aspects, previous prostate bioptical results (histology) and side effects.
Results: PSA levels weren\u2019t subjected to an increase, revealing a stabilizing or downward trend. Percentage of patients with PSA below the level of 4 ng/mL was lower at the end of the study. The overall changes in the uroflowmetry were similar and parallel both in the group with only serenoa repens intake and in the group with serenoa repens plus \u3b1-blocker. The mean medium flow and the mean maximum flow had a slightly increase along the observation time. There was a substantial decreasing in the amount of patients presenting severe prostatic symptoms. Patients reported through the IIEF-5 score a sexual activity substantially unchanged after 6 months of follow-up. The serenoa repens intake resulted in an improvement of the \u201cinflammatory-like reports\u201d, in terms of ultrasound patterns, DRE and bioptical features.
Conclusions: serenoa repens demonstrated its efficacy reducing dysuria with minimal side effects. Further prospective studies might confirm its stabilization or lowering role on PSA levels in this cohort of patients and its possible clinical anti-inflammatory action