Release of muscle α-actin into serum after intensive exercise

Purpose: To study the effects of high-level matches on serum alpha actin and other muscle damage markers in teams of rugby and handball players. Methods: Blood samples were drawn from 23 sportsmen: 13 rugby players and 10 handball players. One sample was drawn with the player at rest before the match and one immediately after the match. Immunoassays were used to determine troponin I, troponin T, LDH, and myoglobin concentrations. Western blot and densitometry were used to measure α-actin concentrations. Muscle injury was defined by a total CK value of > 500 IU/L (Rosalki method). Results: Mean pre- and post-match serum alpha-actin values were, respectively, 7.16 and 26.47 μg/ml in the handball group and 1.24 and 20.04 μg/ml in the rugby team. CPK, LDH and myoglobin but not troponin 1 levels also significantly differed between these time points. According to these results, large amounts of α-actin are released into peripheral blood immediately after intense physical effort. Possible cross-interference between skeletal and cardiac muscle damage can be discriminated by the combined use of α-actin and troponin I. Conclusion: The significant increase in alpha-actin after a high-level match may be a reliable marker for the early diagnosis and hence more effective treatment of muscle injury

Utilidad diagnóstica de los marcadores de estrés oxidativo en artritis reumatoide precoz en pacientes no fumadores y anti-CCP negativos

Fundamento. A pesar del desarrollo de nuevos marcadores y cri- terios diagnósticos para la artritis reumatoide (AR), todavía mu- chos pacientes son diagnosticados tras varios años de síntomas. Los marcadores de estrés oxidativo se incrementan ya en una fase temprana de la enfermedad. El objetivo del presente estudio fue evaluar el valor diagnóstico adicional de estos marcadores. Método. Se realizó un estudio de casos y controles. Los pacien- tes reclutados para el estudio cumplían los criterios para AR de la ACR 1987, todos ellos tenían menos de 2 años de síntomas y sin tratamiento previo con fármacos modificadores de la enfer- medad antirreumática (DMARD), esteroides o vitamina E. Los controles fueron seleccionados de los familiares del paciente y pareados (1:1) por sexo, edad, hábito tabáquico actual. Los marcadores de daño oxidativo que se midieron fueron malo- nildialdehído (MDA), hidroperóxidos lipídicos (LOOH) y pro- teínas carboniladas (CP). El Análisis estadístico se realizó de acuerdo con la STARD. resultados. Se incluyeron sesenta y cinco pacientes con AR sin tratamiento y 65 controles sanos. LOOH, CP, los anticuerpos con péctidos citrulinados (anti-CCP) y el factor reumatoide (FR) fueron significativamente mayores en los pacientes, y MDA fue mayor en los controles. Los mismos resultados se obtuvieron en los subgrupos de pacientes que fuman o no, y en anti-CCP positivos o negativos. El valor diagnóstico de los marcadores tradicionales mostró una buena especificidad pero una baja sensibilidad. La construcción de los modelos logísti- cos con la adicción de LOOH y CP aumenta la sensibilidad y el área bajo la curva ROC, especialmente en los no fumadores (66%) y los pacientes negativos ante-CCP (51%). conclusiones. Al incorporar LOOH o CP a los marcadores de la enfermedad tradicionales en AR, bien por separado o ambos conjuntamente, mejoró el diagnóstico de AR, especialmente en los pacientes no fumadores o aquellos con anticuerpos anti- CCP negativos.background. Besides the development of new markers and di- agnostic criteria for rheumatoid arthritis (RA), many patients are still diagnosed after several years of symptoms. Oxidative stress markers are already increased at an early stage of RA. Our aim was to evaluate the additional diagnostic value of these markers. Methods. A case-control study was performed. Patients met the 1987 RA ACR criteria, less than 2 years of symptoms and no previous treatment with disease-modifying anti-rheumatic drugs (DMARD), steroids or vitamin E. Controls were select- ed from patient’s relatives and matched (1:1) by gender, age, and current smoking habit. Oxidative damage markers were malonyldialdehyde (MDA), Lipid hydroperoxides (LOOH) and Carbonyl proteins (CP). Statistical analysis was performed in agreement with the STARD initiative. results. Sixty-five RA patients without treatment and 65 healthy controls were included. LOOH, CP, antibodies against citrullinated peptides (anti-CCP) and rheumatoid factor (RF) were significantly higher in patients, and MDA higher in con- trols. The same results were obtained in the subgroups of pa- tients who smoke or not, and in anti-CCP positive or negative. The diagnosis performance of traditional markers showed good specificity but low sensitivity. The addition of LOOH and CP increased the sensitivity and the area under the receiving operating characteristic (ROC) curve especially in non-smok- ing (66%) and negative anti-CCP (51%) patients. conclusions. The separate or combined addition of LOOH or CP to the traditional disease markers improved the diag- nosis of RA, especially in non-smoking or negative anti-CCP patients

Association between smoking status and the parameters of vascular structure and function in adults : results from the EVIDENT study

Background: The present study analyses the relation between smoking status and the parameters used to assess vascular structure and function. Methods: This cross-sectional, multi-centre study involved a random sample of 1553 participants from the EVIDENT study. Measurements: The smoking status, peripheral augmentation index and ankle-brachial index were measured in all participants. In a small subset of the main population (265 participants), the carotid intima-media thickness and pulse wave velocity were also measured. Results: After controlling for the effect of age, sex and other risk factors, present smokers have higher values of carotid intima-media thickness (p = 0.011). Along the same lines, current smokers have higher values of pulse wave velocity and lower mean values of ankle-brachial index but without statistical significance in both cases. Conclusions: Among the parameters of vascular structure and function analysed, only the IMT shows association with the smoking status, after adjusting for confounders

Anion-π and lone pair-π interactions with s-tetrazine-based ligands

Most of traditional and contemporary interest in s-tetrazine derivatives focuses onto their redox properties, reactivity and energy density. In recent times, however, an increasing number of reports highlighted the possible usefulness of the s-tetrazine moiety as a binding site for anionic and electron rich species, according to the high and positive quadrupolar moment of this heterocycle and the consequent strength of anion-π and lone pair-π interactions. Herein, after giving a quick perspective on s-tetrazine properties and on how they foster these types of π interactions, we present statistical and critical examination of the available structural data, doing justice to the debated topic of the existence and directionality of anion- and lone pair-π interactions. Finally, available literature material concerning the usage of s-tetrazine as supramolecular binding site in solution, i.e. paving the way to applications such as molecular recognition and sensing, is presented and discussed.Financial support from the Spanish MINECO (project MAT2014- 60104-C2-2-R) and MCIU (RTI2018-101558-B-C21) and from Italian MIUR (project 2015MP34H3) are gratefully acknowledged

Crystal engineering of high explosives through lone pair-p interactions: Insights for improving thermal safety

In this high-risk/high-reward study, we prepared complexes of a high explosive anion (picrate) with potentially explosive s-tetrazine-based ligands with the sole purpose of advancing the understanding of one of the weakest supramolecular forces: the lone pair-p interaction. This is a proof-of-concept study showing how lone pair-p contacts can be effectively used in crystal engineering, even of high explosives, and how the supramolecular architecture of the resulting crystalline phases influences their experimental thermokinetic properties. Herein we present XRD structures of 4 novel detonating compounds, all showcasing lone pair-p interactions, their thermal characterization (DSC, TGA), including the correlation of experimental thermokinetic parameters with crystal packing, and in silico explosion properties. This last aspect is relevant for improving the safety of high-energy materials.The financial support provided by the MUR - Dipartimenti di Eccellenza 2023–2027 (DICUS 2.0) to the Department of Chemistry ‘‘Ugo Schiff’’ of the University of Florence is acknowledged

Supramolecular forces and their interplay in stabilizing complexes of organic anions: tuning binding selectivity in water

How do different supramolecular forces contribute to the stabilization of complexes of organic anions in water? Oftentimes, when debating such a theme, we refer to broad concepts like positive or negative cooperative effects; the focus of the present work is rather on their interplay, i.e. on the way different kinds of stabilizing interactions (salt bridges, H-bonds, anion–π interactions, π–π stacking, solvent effects, etc.) dialogue among themselves. What happens if we tune the strengths of salt bridges by altering the basicity of the anion? What if we change the geometry of the charged group? How does shifting towards more hydrophilic or hydrophobic anions impact the stability of complexes in water? What happens in the solid state? Will aromatic anions go for a π–π stacking or an anion–π interaction mode and do they all behave in the same manner? Does the host/guest size make any difference? What if we play with regiochemistry: will one of the isomers be selectively recognized? Here we present a case study featuring the tetrazine-based ligands L1 and L2 and a series of selected organic anions; potentiometric, NMR, and XRD data and in silico simulations are employed to render such a complex picture.Financial support from the Italian MIUR (project 2015MP34H3) and from the Spanish MINECO (project MAT2014-60104-C2-2-R) is gratefully acknowledged

Halide and hydroxide anion binding in water

The formation of halide and hydroxide anion complexes with two ligands L1 (3,6-bis(morpholin-4- ylmethyl)-1,2,4,5-tetrazine) and L2 (3,6-bis(morpholin-4-ylethyl)-1,2,4,5-tetrazine) was studied in aqueous solution, by means of potentiometric and ITC procedures. In the solid state, HF2 −, Cl− and Br− complexes of H2L22+ were analysed by single crystal XRD measurements. Further information on the latter was obtained with the use of density functional theory (DFT) calculations in combination with the polarizable continuum model (PCM). The presence of two halide or bifluoride HF2 − (F–H–F−) anions forming anion–π interactions, respectively above and below the ligand tetrazine ring, is the leitmotiv of the [(H2L2)X2] (X = HF2, Cl, Br, I) complexes in the solid state, while hydrogen bonding between the anions and protonated morpholine ligand groups contributes to strengthen the anion–ligand interaction, in particular in the case of Cl− and Br−. In contrast to the solid state, only the anion : ligand complexes of 1 : 1 stoichiometry were found in solution. The stability of these complexes displays the peculiar trend I− > F− > Br− > Cl− which was rationalized in terms of electrostatic, hydrogen bond, anion–π interactions and solvent effects. DFT calculations performed on [(H2L2)X]+ (X = F, Cl, Br, I) in PCM water suggested that the ligand assumes a U-shaped conformation to form one anion–π and two salt bridge interactions with the included anions and furnished structural information to interpret the solvation effects affecting complex formation. The formation of hydroxide anion complexes with neutral (not protonated) L1 and L2 molecules represents an unprecedented case in water. The stability of the [L(OH)]− (L = L1, L2) complexes is comparable to or higher than the stability of halide complexes with protonated ligand molecules, their formation being promoted by largely favourable enthalpic contributions that prevail over unfavourable entropic changes.Financial support from the Italian MIUR (project 2015MP34H3) and from the Spanish MINECO (project MAT2014-60104-C2-2-R) is gratefully acknowledged. The centre of instrumental facilities, STI, of the University of Jaén is acknowledged for technical assistance. FP acknowledges the Department of Applied Chemistry of the Graduate School of Engineering of Tohoku University for financial support