Metal-free synthesis of N-fused quinazolino-quinazoline-diones as a RNA triple helix intercalator.

The development of chemical scaffolds that target highly conserved RNA received attention due to its significance in splicing, nuclear organization, and gene expression in disease progression pathways. Here, we synthesized a series of N-fused quinazolino-quinazoline-diones a PIDA-induced C-N coupling methodology to target . Interestingly, compound 2z binds to the UUG pocket of a RNA triple-helix through intercalation, evidenced from molecular docking studies, fluorescence-based assay and CD experiments.

Copper(II)-Mediated Dual Reactivity of 2-(5-Phenylisoxazol-3-yl)aniline: Directed Amination and Oxidative C(═O)─C Cleavage of Amides Enabling Direct Access to Urea Derivatives.

The dual reactivity of amides fused to 2-(5-phenylisoxazol-3-yl)aniline as a directing group for the formation of urea derivatives via chemospecific cleavage of the C(═O)─C bond and C(sp)-H amination is reported here. Employing inexpensive copper as the catalyst and O in air as the oxidant, this protocol exhibited broad functional group tolerance for both the transformations. Detailed mechanistic studies and DFT calculations were performed to gain insights into a plausible mechanism for the formation of urea derivatives.

Synthesis of N-Fused Triazole-Piperazine-Quinazolinones via One-Pot Tandem Click Reaction and Cross-Dehydrogenative Coupling.

Herein, a one-pot protocol to synthesize tetracyclic triazole-piperazine-quinazolinone-fused N-heterocyclic scaffolds is reported. In this strategy, a tandem approach of two highly efficient synthetic reactions, click and cross-dehydrogentive coupling reactions, with high atom economy were employed to obtain the target N-fused scaffolds. Being highly functional group tolerable, this method has broad substrate scope.

Synthetic and Computational Studies on Rh-Catalyzed Redox-Neutral Cascade of Carbenoid Functionalization and Dephosphonylative Annulation.

A Rh(III)-catalyzed regioselective redox-neutral cascade process of carbenoid functionalization followed by dephosphonylative annulation of benzoic acids with α-diazo-β-keto phosphonate has been realized, which led to the direct synthesis of a privileged 3-substituted isocoumarin scaffold. To the best of our knowledge, this is the first report of a complete redox neutral method to synthesize isocoumarins using C-H functionalization strategy. In the catalytic cycle of this reaction, there are two possible pathways for the C-C coupling between ortho-positioned carbon atom of benzoic acid and the diazo carbon atom: (i) concerted 1,2-aryl shift and (ii) stepwise metal-carbene formation followed by migratory insertion.

The effect of patient-prosthesis mismatch on survival after aortic and mitral valve replacement: a 10 year, single institution experience.

Background: The evidence on the impact of patient-prosthesis Mismatch (PPM) on survival thus far has been conflicting. The aim of this study was to 1) study the effect of PPM on survival after isolated aortic and mitral valve replacement and 2) Assess the interaction between left ventricular function and PPM on survival.

Methods: The study cohort was patients who underwent isolated Aortic valve replacement (AVR) and Mitral valve replacement (MVR) over a 10-year period from 2008 to 2018.

Acute Traumatic Right to Left Cardiac Shunt.

Cardiac injuries after penetrating chest trauma are uncommon but potentially life threatening; these injuries can remain occult during the early stage because of the cardiac reserve of youthful physiology and may present at a later stage as the initial damage progresses or compensatory mechanisms fail. We report a case of unusual penetrating cardiac trauma from a posterior intercostal stab wound that affected both the interatrial septum and the tricuspid valve, leading to a stormy presentation as a result of the development of an acute right-to-left shunt followed by a successful surgical repair.

The use of 3D transoesophageal echocardiography in clarifying the mechanism underlying a 'flexing' strut of a mitral valve replacement.

We report the case of a 76-year-old lady who had a mitral valve (MV) replacement for severe MV stenosis. Several days following the procedure, a routine transthoracic echocardiogram (TTE) was performed. Despite the prosthesis leaflets opening well anterograde maximum velocities were elevated; MV peak velocity of 2.

Vascular stiffness is related to superoxide generation in the vessel wall.

Objectives: Oxidative stress causes endothelial dysfunction and plays a major role in the pathogenesis of cardiovascular disease. Increased vascular stiffness is an intermediate phenotype in the development of cardiovascular disease. We hypothesized that vascular stiffness is partially determined by oxidative stress.

Post myocardial infarction left ventricular free wall rupture.

Occurrence of left ventricular free wall rupture following myocardial infarction is an unpredictable event associated with very high mortality rate. The most appropriate surgical approach remains controversial. With recent advances in portable echocardiography machines there has been a progressive rise in the number of cases of left ventricular free wall rupture diagnosed and reported.

Effects of gelatine and medium molecular weight starch as priming fluid in cardiopulmonary bypass--a randomised controlled trial.

Perioperative volume replacement after cardiopulmonary bypass is complicated by post-bypass systemic inflammatory process. The aim of this study was to assess the effects of using two different colloid solutions as priming fluids in cardiopulmonary bypass. The study's primary end point was to measure the amount of fluid replacement needed during and post-cardiopulmonary bypass; blood loss, change in blood profile and intraocular pressure were secondary end points, used as measures of plasma oncotic pressures.

Mitral valve replacement for mitral stenosis secondary to Hunter's syndrome.

Hunter's syndrome is a rare, X-linked recessive, mucopolysaccharidosis. Survival into adulthood is uncommon. Mitral valve disease, predominantly regurgitation, has been reported in these patients.

Left atrial myxoma in transplanted heart.

Primary cardiac tumours are discovered in about 1 in 2000 necropsies. Cardiac myxomas make up half of all benign intracardiac tumours. Seventy five per cent are located in the left atrium.

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function.

Background: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively.

Methods: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H).

Vasorelaxant properties of isolated human radial arteries: comparison with internal mammary arteries.

Radial arteries, used in revascularisation surgery, are prone to spasm. We have examined the ability of nitrovasodilators, calcium channel blockers, and K(ATP) channel openers to cause vasodilation, and to attenuate contractions due to depolarisation and receptor activation in radial and mammary arteries used in coronary artery bypass graft surgery. Two to three millimetre rings of artery obtained from patients at surgery were studied in organ baths in vitro.

Six-year follow-up of the Toronto stentless porcine valve.

Stentless valves in the aortic position have been shown to have superior hemodynamic performance to stented valves and have now been shown to increase survival. We report the medium-term results from a single center of 229 Toronto (SPV) aortic valve replacements between 1994 and 2000. The mean age of the patients was 72 years (range, 41-87 years).

The aortic Elan stentless aortic valve: excellent hemodynamics and ease of implantation.

The superior performance of stentless aortic valves with improved left ventricular hypertrophy regression and greater effective orifice area is proven. The Aortech Elan stentless valve (AESV) is a glutraldehyde preserved porcine valve with a pericardial reinforced inflow tract and a scalloped outflow to reduce bulk. We present the early results of AESV implantation at our institution.

Is hydrogen peroxide an EDHF in human radial arteries?

In human radial arteries, a nitric oxide/prostanoid-independent mechanism that has the pharmacological characteristics of an EDHF contributes to endothelium-dependent relaxation. H2O2 can act as an EDHF in some vascular beds. We examined the hypothesis that endogenously produced H2O2 mediated the nitric oxide/prostanoid-independent relaxation to carbachol in radial arteries obtained from patients undergoing coronary artery bypass surgery.

Randomized controlled trial of stented and stentless aortic bioprotheses: hemodynamic performance at 3 years.

A randomized prospective trial was undertaken to compare the hemodynamic performance and left ventricular regression after aortic valve replacement with the Toronto SPV stentless bioprosthesis and the Carpentier Edwards SAV (CE) bioprosthesis. Forty patients were randomized after the annular and sinotubular diameters had been measured. Early hemodynamic measurements were made with a thermodilution cardiac output catheter, and echocardiography was used thereafter.

Pharmacological characterisation of endothelium-dependent relaxation in human radial artery: comparison with internal thoracic artery.

Objective: The aim of this study was to investigate the contribution of nitric oxide/prostanoid-independent pathways to endothelium-dependent vasorelaxation in human conduit arteries.

Methods: Rings of internal thoracic artery (ITA) and radial artery (RA) taken from patients undergoing coronary artery bypass graft surgery were suspended in 10-ml organ baths and relaxation to carbachol and bradykinin studied in the presence and absence of nitric oxide synthase (NOS) inhibitors and potassium channel blockers.

Results: No significant relaxation to carbachol or bradykinin was observed in ITA after NOS inhibition.

Ventricular remodelling and revascularization in severe left ventricular dysfunction.

Objective: To evaluate the role of surgical revascularization in the presence of severe, global impairment of left ventricular function without discrete aneurysm formation or mitral regurgitation. The high mortality and morbidity associated with this group, together with the limited benefits tend to prompt referral for cardiac transplantation.

Methods: Fifty-three patients initially referred for transplantation, in addition to coronary revascularization, underwent mitral annuloplasty (group A = 23), free wall remodelling by endoaneurysmorrhaphy (group B = 17) or mitral annuloplasty and free wall reconstruction (group C = 13).

A three year experience with the toronto stentless porcine valve.

In the three year period from March 1994, 112 Toronto Stentless Porcine Valves (SPV TM) were implanted in the Western Infirmary, Glasgow. There were 55 males and 57 females aged between 45 and 86 years (mean 70.9 +/- 7.

Alterations in renal microcirculation during cardiopulmonary bypass.

Background: This study was designed to investigate renal microvascular changes during cardiopulmonary bypass.

Methods: Kidneys were harvested from each of four groups of 6 pigs. Group A were anesthetized and heparinized only.

Breaking the rules! Cardiac injury from remote entry sites.

An unusual case of penetrating injury to the heart is reported. This presented late, after an initial silent period. A high index of suspicion must be maintained when chest injuries are managed conservatively.

Osteonecrosis of the calcaneum in a heart transplant recipient.

Avascular necrosis affects 3% of transplant recipients. In the lower limb, the femoral heads or condyles may be involved. We report the hitherto unrecorded complication of avascular necrosis of the calcaneum.