Haematic antegrade repriming to enhance recovery after cardiac surgery from the perfusionist side.

Background: New era of cardiac surgery aims to provide an enhanced postoperative recovery through the implementation of every step of the process. Thus, perfusion strategy should adopt evidence-based measures to reduce the impact of cardiopulmonary bypass (CPB). Hematic Antegrade Repriming (HAR) provides a standardized procedure combining several measures to reduce haemodilutional priming to 300 mL. Once the safety of the procedure in terms of embolic release has been proven, the evaluation of its beneficial effects in terms of transfusion and ICU stay should be assessed to determine if could be considered for inclusion in Enhanced Recovery After Cardiac Surgery (ERACS) programs. Methods: Two retrospective and non-randomized cohorts of high-risk patients, with similar characteristics, were assessed with a propensity score matching model. The treatment group (HG) (n = 225) received the HAR. A historical cohort, exposed to conventional priming with 1350 mL of crystalloid confirmed the control group (CG) (n = 210). Results: Exposure to any transfusion was lower in treated (66.75% vs. 6.88%, p < 0.01). Prolonged mechanical ventilation (>10 h) (26.51% vs. 12.62%; p < 0.01) and extended ICU stay (>2 d) (47.47% vs. 31.19%; p < 0.01) were fewer for treated. HAR did not increase early morbidity and mortality. Related savings varied from 581 to 2741.94 $/patient, depending on if direct or global expenses were considered. Discussion: By reducing the gaseous and crystalloid emboli during CPB initiation, HAR seems to have a beneficial impact on recovery and reduces the overall transfusion until discharge, leading to significant cost savings per process. Due to the preliminary and retrospective nature of the research and its limitations, our findings should be validated by future prospective and randomized studies.

Accessory left atrial cords: A case report and literature review.

INTRODUCTION: Accessory left atrial cords are fibroelastic structures found in the left atrium. Left atrial cords may be associated with mitral valve disease, atrial fibrillation, stroke, and other congenital left-side anomalies. METHODS: We presented the case of a man with severe Mitral Regurgitation and two accessories left atrial cords attached to P2 scallop by a single tendon and performed a literature review using PUBMED/MEDLINE, Web of Science, and EMBASE databases on December 4, 2021. RESULTS: According to our review, accessory left atrial cords were found more frequently in women (36 patients, 62%), more frequently attached to the mitral valve (66% of reports) and mitral regurgitation was the most frequently reported pattern of mitral valve disease (64.2%). No other cases of double left atrial cords attached to P2 segment were found. CONCLUSION: Accessory left atrial chords may be related to mitral valve disease and other left-side congenital abnormalities. These structures were found more frequently in females and A2 insertion was the most frequently observed pattern in the review.

Fishing for G-Quadruplexes in Solution with a Perylene Diimide Derivative Labeled with Biotins.

A new fluorescent, non-cytotoxic perylene diimide derivative with two biotins at the peri position, PDI2B, has been synthesized. This molecule is able to interact selectively with G-quadruplexes with scarce or no affinity towards single- or double-stranded DNA. These features have made it possible to design a simple, effective, safe, cheap, and selective method for fishing G-quadruplex structures in solution by use of PDI2B and streptavidin coated magnetic beads. The new cyclic method reported leads to the recovery of more than 80 % of G-quadruplex structures from solution, even in the presence of an excess of single-stranded or duplex DNA as competitors. Moreover, PDI2B is a G4 ligand that can display higher thermal stabilization and greater affinity for 2- over 3-tetrad quadruplexes, which constitutes a novel type of behavior.

Kinetic evidence for interaction of TMPyP4 with two different G-quadruplex conformations of human telomeric DNA.

BACKGROUND: Stabilization of G-quadruplex helices by small ligands has attracted growing attention because they inhibit the activity of the enzyme telomerase, which is overexpressed in >80% cancer cells. TMPyP4, one of the most studied G-quadruplex ligands, is used as a model to show that the ligands can exhibit different binding features with different conformations of a human telomeric specific sequence. METHODS: UV-Vis, FRET melting Assay, Isothermal Titration Calorimetry, Time-resolved Fluorescence lifetime, T-Jump and Molecular Dynamics. RESULTS: TMPyP4 yields two different complexes with two Tel22 telomeric conformations in the presence of Na+ or K+. T-Jump kinetic experiments show that the rates of formation and dissociation of these complexes in the ms time scale differ by one order of magnitude. MD simulations reveal that, in K+ buffer, "hybrid 1" conformation yields kinetic constants on interaction with TMPyP4 one order lower than "hybrid 2". The binding involves π-π stacking with external loop bases. CONCLUSIONS: For the first time we show that for a particular buffer TMPyP4 interacts in a kinetically different way with the two Tel22 conformations even if the complexes formed are thermodynamically indistinguishable. GENERAL SIGNIFICANCE: G-quadruplexes, endowed with technological applications and potential impact on regulation mechanisms, define a new research field. The possibility of building different conformations from same sequence is a complex issue that confers G-quadruplexes very interesting features. The obtaining of reliable kinetic data constitutes an efficient tool to determine reaction mechanisms between conformations and small molecules.

Strong Influence of Ancillary Ligands Containing Benzothiazole or Benzimidazole Rings on Cytotoxicity and Photoactivation of Ru(II) Arene Complexes.

A new family of neutral ruthenium(II) arene complexes of the type [Ru(η6-arene)X(κ2- O, N-L)] (η6-arene = p-cym, bz; X = Cl-, SCN-; HL1 = 2-(2'-hydroxyphenyl)benzimidazole, HL2 = 2-(2'-hydroxyphenyl)benzothiazole) has been synthesized and characterized. The cytotoxic activity of the Ru(II) complexes was evaluated in several tumor cell lines (A549, HepG2 and SW480) both in the dark and after soft irradiation with UV and blue light. None of the complexes bearing benzimidazole (HL1) as a ligand displayed phototoxicity, whereas the complexes with a benzothiazole ligand (HL2) exhibited photoactivation; the sensitivity observed for UV was higher than for blue light irradiation. The interesting results displayed by HL2 and [Ru(η6- p-cym)(NCS)(κ2- O, N-L2)], [3a], in terms of photo cytotoxicity prompted us to analyze their interaction with DNA, both in the dark and under irradiation conditions, in an effort to shed some light on their mechanism of action. The results of this study revealed that HL2 interacts with DNA by groove binding, whereas [3a] interacts by a dual mode of binding, an external groove binding, and covalent binding of the metal center to the guanine moiety. Interestingly, both HL2 and [3a] display a clear preference for AT base pairs, and this causes fluorescence enhancement. Additionally, cleavage of the pUC18 plasmid DNA by the complex is observed upon irradiation. The study of the irradiated form demonstrates that the arene ligand is released to yield species such as [Ru(κ2- O, N-L2)(κ1- S-DMSO)2(µ-SCN)]2 [3c] and [Ru(κ2- O, N-L2)(κ1- S-DMSO)3(SCN)] [3d]. Such photo dissociation occurs even in the absence of oxygen and leads to cytotoxicity enhancement, an effect attributed to the presence of [3d], thus revealing the potential of [3a] as a pro-drug for photoactivated anticancer chemotherapy (PACT).

Role of Seroalbumin in the Cytotoxicity of cis-Dichloro Pt(II) Complexes with (N

Given the potent anticancer properties of cis-diamminedichloroplatinum(II) and knowing its mode of action, we synthesized four new cis-[PtCl2(N^N)] organoplatinum complexes, two with N-substituted pbi ligands (pbiR = 1-R-2-(2-pyridyl)benzimidazole) (namely, 1 and 2) and two more with 4,4'-disubstituted bpy ligands (bpy = 2,2'-bipyridine) (namely, 3 and 4). We explored their cytotoxicity and ability to bind to deoxyguanosine monophosphate (dGMP), DNA, and albumin models. By 1H NMR and UV-vis spectroscopies, circular dichroism, agarose gel electrophoresis, differential scanning calorimetry measurements, and density functional theory calculations, we verified that only 3 can form aquacomplex species after dimethyl sulfoxide solvation; surprisingly, 1, 2, and 3 can bind covalently to DNA, whereas 4 can form a noncovalent complex. Interestingly, only complexes 1 and 4 exhibit good cytotoxicity against human ovarian carcinoma (HeLa) cell line, whereas 2 and 3 are inactive. Although lung carcinoma (A549) cells are more resistant to the four platinum complexes than HeLa cells, when the protein concentration in the extracellular media is lower, the cytotoxicity becomes substantially enhanced. By native electrophoresis of bovine seroalbumin (BSA) and inductively coupled plasma mass spectrometry uptake studies we bear out, on one hand, that 2 and 3 can interact strongly with BSA and its cellular uptake is negligible and, on the other hand, that 1 and 4 can interact with BSA only weakly, its cellular uptake being higher by several orders. These results point up the important role of the protein binding features on their biological activity and cellular uptake of cis-"PtCl2" derivatives. Our results are valuable in the future rational design of new platinum complexes with improved biological properties, as they expose the importance not only of their DNA binding abilities but also of additional factors such as protein binding.

Unequal effect of ethanol-water on the stability of ct-DNA, poly[(dA-dT)]2 and poly(rA)·poly(rU). Thermophysical properties.

Ethanol affects unequally the thermal stability of DNA and RNA. It stabilizes RNA, while destabilizing DNA. The variation of the relative viscosity (η/η0) of [poly(dA-dT)]2 with temperature unveils transitions close to the respective denaturation temperature, calculated spectrophotometrically and calorimetrically. From the raw data densities and speeds of sound, the volumetric observables were calculated. In all cases studied, a change in sign from low to high ethanol content occurred for both partial molar volume (ϕV) and partial molar adiabatic compressibility (ϕK(S)). The minima, close to 10%, should correspond to the highest solvation and the maxima, close to 30%, to the lowest solvation. For 40-50% ethanol, the solvation increases again. The complex structure of ethanol-water, for which changes are observed in regions close to such critical concentrations, justifies the observed behaviour. The variation of ϕV and ϕK(S) was sharper for RNA compared with respect to DNA, indicating that the solvation sequence is poly(rA)·poly(rU) < ct-DNA < [poly(dA-dT)]2.

Stabilization of Al(III) solutions by complexation with cacodylic acid: speciation and binding features.

Aluminium ions are believed to play a role in a number of neurological and skeletal disorders in the human body. The study of the biological processes and molecular mechanisms that underlie these pathological disorders is rendered a difficult task due to the wide variety of complex species that result from the hydrolysis of Al(3+) ions. In addition, this ion displays a pronounced tendency to precipitate as a hydroxide, so certain complexing agents should be envisaged to stabilize Al(III) solutions in near physiological conditions. In this work, we show that the common buffer cacodylic acid (dimethylarsinic acid, HCac) interacts with Al(III) to give stable complexes, even at pH 7. After preliminary analyses of the speciation of the metal ion and also of the ligand, a systematic study of the formation of different Al/Cac complexes at different pH values has been conducted. UV-Vis titrations, mass spectrometry NMR measurements and DTF calculations were performed to enlighten the details of the speciation and stoichiometry of Al/Cac complexes. The results altogether show that Al/Cac dimer complexes prevail, but monomer and trimer forms are also present. Interestingly, it was found that cacodylate promotes the formation of such relatively simple complexes, even under conditions where the polymeric form, Al13O4(OH)24(7+), should predominate. The results obtained can help to shed some light into the reactivity of aluminium ions in biological environments.

Ag2 and Ag3 clusters: synthesis, characterization, and interaction with DNA.

Subnanometric samples, containing exclusively Ag2 and Ag3 clusters, were synthesized for the first time by kinetic control using an electrochemical technique without the use of surfactants or capping agents. By combination of thermodynamic and kinetic measurements and theoretical calculations, we show herein that Ag3 clusters interact with DNA through intercalation, inducing significant structural distortion to the DNA. The lifetime of Ag3 clusters in the intercalated position is two to three orders of magnitude longer than for classical organic intercalators, such as ethidium bromide or proflavine.

Derivation of structure-activity relationships from the anticancer properties of ruthenium(II) arene complexes with 2-aryldiazole ligands.

The ligands 2-pyridin-2-yl-1H-benzimidazole (HL(1)), 1-methyl-2-pyridin-2-ylbenzimidazole (HL(2)), and 2-(1H-imidazol-2-yl)pyridine (HL(3)) and the proligand 2-phenyl-1H-benzimidazole (HL(4)) have been used to prepare five different types of new ruthenium(II) arene compounds: (i) monocationic complexes with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL)]Y [HL = HL(1), HL(2), or HL(3); Y = Cl or BF4; arene = 2-phenoxyethanol (phoxet), benzene (bz), or p-cymene (p-cym)]; (ii) dicationic aqua complexes of the formula [(η(6)-arene)Ru(OH2)(κ(2)-N,N-HL(1))](Y)2 (Y = Cl or TfO; arene = phoxet, bz, or p-cym); (iii) the nucleobase derivative [(η(6)-arene)Ru(9-MeG)(κ(2)-N,N-HL(1))](PF6)2 (9-MeG = 9-methylguanine); (iv) neutral complexes consistent with the formulation [(η(6)-arene)RuCl(κ(2)-N,N-L(1))] (arene = bz or p-cym); (v) the neutral cyclometalated complex [(η(6)-p-cym)RuCl(κ(2)-N,C-L(4))]. The cytototoxic activity of the new ruthenium(II) arene compounds has been evaluated in several cell lines (MCR-5, MCF-7, A2780, and A2780cis) in order to establish structure-activity relationships. Three of the compounds with the general formula [(η(6)-arene)RuCl(κ(2)-N,N-HL(1))]Cl differing in the arene moiety have been studied in depth in terms of thermodynamic dissociation constants, aquation kinetic constants, and DNA binding measurements. The biologically most active compound is the p-cym derivative, which strongly destabilizes the DNA double helix, whereas those with bz and phoxet have only a small effect on the stability of the DNA double helix. Moreover, the inhibitory activity of several compounds toward CDK1 has also been evaluated. The DNA binding ability of some of the studied compounds and their CDK1 inhibitory effect suggest a multitarget mechanism for their biological activity.

RNA triplex-to-duplex and duplex-to-triplex conversion induced by coralyne.

Spectrophotometric, circular dichroism, calorimetric, displacement assay and kinetic analyses of the binding of the fluorescent dye coralyne to poly(A)2poly(U) have served to enlighten the ability of the dye to produce dramatic changes in the RNA structure. The sets of data assembled convey that coralyne is able to induce the triplex-to-duplex conversion and also the duplex-to-triplex conversion according to a non-reversible cycle governed by temperature, provided that the [dye]/[polymer] ratio (CD/CP) is maintained constant above unity. Alternatively, at room temperature the triplex is formed at (roughly) CD/CP < 1 and the duplex at CD/CP > 1.

Anticancer activity and DNA binding of a bifunctional Ru(II) arene aqua-complex with the 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine ligand.

The synthesis and full characterization of the new aqua-complex [(η(6)-p-cymene)Ru(OH2)(κ(2)-N,N-2-pydaT)](BF4)2, [2](BF4)2, and the nucleobase derivative [(η(6)-p-cymene)Ru(9-MeG)(κ(2)-N,N-2-pydaT)](BF4)2, [4](PF6)2, where 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine and 9-MeG = 9-methylguanine, are reported here. The crystal structures of both [4](PF6)2 and the chloro complex [(η(6)-p-cymene)RuCl(κ(2)-N,N-2-pydaT)](PF6), [1](PF6), have been elucidated by X-ray diffraction. The former provided relevant information regarding the interaction of the metallic fragment [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) and a simple model of DNA. NMR and kinetic absorbance studies have proven that the aqua-complex [2](BF4)2 binds to the N7 site of guanine in nucleobases, nucleotides, or DNA. A stable bifunctional interaction (covalent and partially intercalated) between the [(η(6)-p-cymene)Ru(κ(2)-N,N-2-pydaT)](2+) fragment and CT-DNA has been corroborated by kinetic, circular dichroism, viscometry, and thermal denaturation experiments. The reaction mechanism entails the very fast formation of the Ru-O-(PO3) linkage prior to the fast intercalation of the 2-pydaT fragment. Then, a Ru-N7-(G) covalent bond is formed at the expense of the Ru-O-(PO3) bond, yielding a bifunctional complex. The dissociation rate of the intercalated fragment is slow, and this confers additional interest to [2](BF4)2 in view of the likely correlation between slow dissociation and biological activity, on the assumption that DNA is the only biotarget. Furthermore, [2](BF4)2 displays notable pH-dependent cytotoxic activity in human ovarian carcinoma cells (A2780, IC50 = 11.0 µM at pH = 7.4; IC50 = 6.58 µM at pH = 6.5). What is more, complex [2](BF4)2 is not cross-resistant with cisplatin, exhibiting a resistance factor, RF(A2780cis), of 0.28, and it shows moderate selectivity toward the cancer cell lines, in particular, A2780cis (IC50 = 3.0 5 ± 0.08 µM), relative to human lung fibroblast cells (MRC-5; IC50 = 24 µM), the model for healthy cells.

Outcomes of rapid deployment aortic valve replacement with concomitant cardiac procedures.

Background: Rapid deployment aortic valve replacement (RD-AVR) has been recently introduced with encouraging results. Outcomes of isolated RD-AVR include good hemodynamic profile, facilitation of minimally invasive techniques, and reduction of surgical times. However, role of this prosthesis in concomitant surgery is not well known. Methods: In 2016, we formed a registry to monitor the introduction of this prosthesis, RApid Deployment Aortic Replacement (RADAR). We aim to report mid-term outcomes focusing on patients who had RD-AVR combined with other surgical procedures. Results: Between July 2012 and February 2021, 370 patients were included in this registry (mean age, 75.8±8.0 years; 64.32% male; mean EuroSCORE II, 3.5±2.8). Of these, 128 (34.59%) had concomitant procedures including myocardial revascularization surgery in 69 patients (53.91%), surgery on the ascending aorta in 34 (26.56%), and procedures on other valves in 10 patients (7.81%). There were no significant differences between the isolated AVR and concomitant AVR groups in postoperative complications, in-hospital mortality (4.72% vs. 3.32%, P=0.524), or hemodynamic behavior of these prostheses. Three-year survival was 83.73% and 89.89% in the isolated and concomitant AVR group respectively. There was no difference in survival between the two groups (log-rank test, P=0.4124). Conclusions: Our results support the safety and efficacy of the Edwards INTUITY valve system even in complex aortic valve disease with additional cardiac procedures. RD-AVR could become a useful tool for concomitant surgeries where surgical times are expected to be prolonged.

The mode of binding ACMA-DNA relies on the base-pair nature.

A thermodynamic and kinetic study on the mode of binding of 9-amino-6-chloro-2-methoxi-acridine (ACMA) to poly(dA-dT)·poly(dA-dT) and poly(dG-dC)·poly(dG-dC) has been undertaken at pH = 7.0 and I = 0.1 M. The spectrophotometric, kinetic (T-jump), circular dichroism, viscometric and calorimetric information gathered point to formation of a fully intercalated ACMA complex with poly(dA-dT)·poly(dA-dT) and another one only partially intercalated (7%) with poly(dG-dC)·poly(dG-dC). The ACMA affinity with the A-T bases was higher than with the G-C bases. The two polynucleotide sequences give rise to external complexes when the ACMA concentration is raised, namely, the electrostatic complex poly(dA-dT)·poly(dA-dT)-ACMA and the major groove binding complex poly(dG-dC)·poly(dG-dC)-ACMA. A considerable quenching effect of the ACMA fluorescence is observed with poly(dA-dT)·poly(dA-dT), ascribable to face-to-face location in the intercalated A-T-ACMA base-pairs. The even stronger effect observed in the presence of poly(dG-dC)·poly(dG-dC) is related to the guanine residue from on- and off-slot ACMA positions.

New aspects of the interaction of the antibiotic coralyne with RNA: coralyne induces triple helix formation in poly(rA)*poly(rU).

The interaction of coralyne with poly(A)*poly(U), poly(A)*2poly(U), poly(A) and poly(A)*poly(A) is analysed using spectrophotometric, spectrofluorometric, circular dichroism (CD), viscometric, stopped-flow and temperature-jump techniques. It is shown for the first time that coralyne induces disproportionation of poly(A)*poly(U) to triplex poly(A)*2poly(U) and single-stranded poly(A) under suitable values of the [dye]/[polymer] ratio (C(D)/C(P)). Kinetic, CD and spectrofluorometric experiments reveal that this process requires that coralyne (D) binds to duplex. The resulting complex (AUD) reacts with free duplex giving triplex (UAUD) and free poly(A); moreover, ligand exchange between duplex and triplex occurs. A reaction mechanism is proposed and the reaction parameters are evaluated. For C(D)/C(P)> 0.8 poly(A)*poly(U) does not disproportionate at 25 degrees C and dye intercalation into AU to give AUD is the only observed process. Melting experiments as well show that coralyne induces the duplex disproportionation. Effects of temperature, ionic strength and ethanol content are investigated. One concludes that triplex formation requires coralyne be only partially intercalated into AUD. Under suitable concentration conditions, this feature favours the interaction of free AU with AUD to give the AUDAU intermediate which evolves into triplex UAUD and single-stranded poly(A). Duplex poly(A)*poly(A) undergoes aggregation as well, but only at much higher polymer concentrations compared to poly(A)*poly(U).

Route to metallacrowns: the mechanism of formation of a dinuclear iron(III)-salicylhydroxamate complex.

The equilibria and the kinetics of the binding of Iron(III) to salicylhydroxamic (SHA) and benzohydroxamic (BHA) acids have been investigated in aqueous solution (I = 1 M (HClO(4)/NaClO(4)), T = 298 K) using spectrophotometric and stopped-flow methods. Whereas Iron(III) forms a 1:1 complex (ML) with BHA, it forms both ML and M(2)L complexes with SHA. The presence of M(2)L in aqueous medium is corroborated by FTIR measurements. The reactive form of Iron(III) is the hydrolyzed species FeOH(2+), which binds to the O,O site in ML and to the O,O and O(P),N (P = phenolate) sites in M(2)L, inducing full deprotonation of the latter. The reaction pathway is discussed in terms of a multistep mechanistic scheme in which the metal-ligand interaction is coupled to hydrolysis and self-aggregation steps of Iron(III). The observation and characterization of M(2)L as a stable species is important because it contains the -Fe-O-N-Fe- sequence, which constitutes the repetitive motif of the SHA-based metallacrown ring and provides the rationale for 12-MC-4 metallacrowns. In the framework of this study, the kinetics of the Iron(III) dimerization and trimerization have also been investigated using the stopped-flow method to perform dilution jumps. The reaction scheme put forward involves two parallel steps (FeOH(2+) + FeOH(2+) and Fe(3+) + FeOH(2+)) that lead to formation of the Fe(2)(OH)(2)(4+) dimer and a slower step (FeOH(2+) + Fe(2)(OH)(2)(4+)) to form the trimer species. The kinetics of the last step have been investigated here for the first time, and the results deduced indicate that, of the two possible trimer structures reported in the literature, Fe(3)(OH)(3)(6+) and Fe(3)(OH)(4)(5+), the latter prevails by far.

ACMA (9-amino-6-chloro-2-methoxy acridine) forms three complexes in the presence of DNA.

The interaction of ACMA (9-amino-6-chloro-2-methoxy acridine) (D) with DNA (P) has been studied by absorbance, fluorescence, circular dichroism, spectrophotometry, viscometry and unwinding electrophoresis. A T-jump kinetic study has also been undertaken. The experimental data show that, totally unlike other drugs, ACMA is able to form with DNA three complexes (PD(I), PD(II), PD(III)) that differ from each other by the characteristics and extent of the binding process. The main features of PD(I) fulfil the classical intercalation pattern and the formation/dissociation kinetics have been elucidated by T-jump techniques. PD(II) and PD(III) are also intercalated species but, in addition to the dye units lodged between base pairs, they also bear dye molecules externally bound, more in PD(III) relative to PD(II). A reaction mechanism is put forward here. Comparison between absorbance, fluorescence and kinetic experiments has enabled us to determine the binding constants of the three complexes, namely (6.5 ± 1.1) × 10(4) M(-1) (PD(I)), (5.5 ± 1.5) × 10(4) M(-1) (PD(II)) and (5.7 ± 0.03) × 10(4) M(-1) (PD(III)). The Comet assay reveals that the ACMA binding to DNA brings about genotoxic properties. The mutagenic potential studied by the Ames test reveals that ACMA can produce frameshift and transversion/transition mutations. ACMA also is able to produce base-pair substitution in the presence of S9 mix. Moreover, the MTT assays have revealed cytotoxicity. The biological effects observed have been rationalized in light of these features.

Mid-term outcomes of rapid deployment aortic prostheses in patients with small aortic annulus.

OBJECTIVES: The Edwards Intuity valve is a rapid deployment aortic prosthesis that favours less invasive approaches. However, evidence about the clinical behaviour of their smaller sizes is scarce. Herein, we studied haemodynamic behaviours and clinical outcomes of small Intuity prostheses (19-21 mm) in comparison to larger Intuity prostheses (>21 mm). METHODS: This is an observational study including patients implanted with an Edwards Intuity rapid deployment aortic prosthesis. Patients with prosthesis sizes 19-21 and >21 mm were included. Baseline and perioperative variables, as well as adverse events during the follow-up were recorded and compared between groups. RESULTS: A total of 122 patients (37% female, mean age 75 ± 4.5 years) were included, of whom 54 (45%) were implanted with a small prosthesis and 68 (55%) with a prosthesis >21 mm. There were no significant differences between patients with small Intuity prostheses and patients with larger prostheses regarding in-hospital mortality (2% vs 4%, P = 0.43) or mortality during the follow-up (3.41 vs 2.45 per 100 patients-years; P = 0.58). Survival in the small Intuity valve group was 95% at 1 year and 83% at 6 years, whereas in the larger Intuity valve group was 96% at 1 year and 78% at 6 years. The presence of a small prosthesis did not influence mid-term survival (log-rank P-value = 0.62). CONCLUSIONS: This study showed good clinical performance of Intuity aortic prostheses with appropriate mid-term survival in patients with the small aortic annulus. Thus, the Edwards Intuity rapid deployment aortic prosthesis may be considered as a potential option in patients with the small aortic annulus.

Biological assays and noncovalent interactions of pyridine-2-carbaldehyde thiosemicarbazonecopper(II) drugs with [poly(dA-dT)](2), [poly(dG-dC)] (2), and calf thymus DNA.

The interaction of the Cu(II) drugs CuL(NO(3)) and CuL'(NO(3)) (HL is pyridine-2-carbaldehyde thiosemicarbazone and HL' is pyridine-2-carbaldehyde 4N-methylthiosemicarbazone, in water named [CuL](+) and [CuL'](+)) with [poly(dA-dT)](2), [poly(dG-dC)](2), and calf thymus (CT) DNA has been probed in aqueous solution at pH 6.0, I = 0.1 M, and T = 25 degrees C by absorbance, fluorescence, circular dichroism, and viscosity measurements. The results reveal that these drugs act as groove binders with [poly(dA-dT)](2), with a site size n = 6-7, whereas they act as external binders with [poly(dG-dC)](2) and/or CT-DNA, thus establishing overall electrostatic interaction with n = 1. The binding constants with [CuL'](+) were slightly larger than with [CuL](+). The title compounds display some cleavage activity in the presence of thiols, bringing about the rupture of the DNA strands by the reactive oxygen species formed by reoxidation of Cu(I) to Cu(II); this feature was not observed in the absence of thiols. Mutagenic assays performed both in the presence and in the absence of S9 mix, probed by the Ames test on TA 98, TA 100, and TA 102, were negative. Weak genotoxic activity was detected for [CuL](+) and [CuL'](+), with a significative dose-response effect for [CuL'](+), which was shown to be more cytotoxic in the Ames test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide cell proliferation assays. Methylation of the terminal NH(2) group enhances the antiproliferative activity of the pyridine-2-carbaldehyde thiosemicarbazones.

Left-handed DNA: intercalation of the cyanine thiazole orange and structural changes. A kinetic and thermodynamic approach.

The conditions under which different structures of left-handed DNA (poly(dG-me(5)dC)·poly(dG-me(5)dC)) can exist are investigated by spectrofluorometric, spectrophotometric, circular dichroism and calorimetric measurements and the kinetics of the transformations are analysed. The effects of temperature, salt and ethanol content on the transitions are also studied. The left-handed structure obtained by addition of either Mg(2+) ions or EtOH corresponds to Z-DNA, whereas the structure obtained using the mixture Mg(2+)/EtOH corresponds to the aggregate Z*-DNA. Upon addition of the fluorescent cyanine Thiazole Orange (TO), the transition Z → B immediately starts, whereas Z*-DNA retains its left-handed configuration in the presence of TO provided that the ratio [dye]/[polymer] ≤ 0.1. The equilibria and kinetics of the TO binding to Z*-DNA are investigated under the above conditions using the T-jump technique. The reaction mechanism consists of two series steps, the first one being characterized by the formation of an external electrostatic complex and the second corresponding to the dye penetration between the base pairs. A comparison with the B-DNA/TO system is drawn.