Rare case of iatrogenic aortic valve leaflet tear following a diagnostic coronary angiogram

We report a rare case of a 44-year-old male who underwent a diagnostic coronary angiogram following a non-ST elevation myocardial infarction complicated by an aortic valve leaflet tear requiring surgical intervention. Routine transthoracic echocardiogram demonstrated a mobile echogenic structure prolapsing into the left ventricular outflow tract. An intraoperative transesophageal echocardiogram confirmed that the structure originated from the ventricular side of left coronary cusp, causing malcoaptation between left and right coronary cusps, and subsequent moderate to severe aortic regurgitation.     

Synthesis of water soluble copper(II) complexes: crystal structures,DNA binding,oxidative DNA cleavage,and in vitro anticancer studies

Two ternary copper(II) complexes of dl-threonine and polypyridyl ligands with formula of [Cu(Thr)(Byp)Cl]·H₂O (1) and [Cu(Thr)(Phen)H₂O]Cl·2H₂O (2) were synthesized. The complexes were characterized by spectral (NMR, FT-IR, and UV–Vis), CHN elemental analysis and have been structurally elucidated by X-ray crystallography. Both of the complexes formed slightly distorted square-pyramidal coordination geometry. The electronic absorption spectra of the complexes showed a very low intensity d–d electronic band in the range of 610–620 nm in Tris–HCl/NaCl (5:5 mM) pH 7.2 buffer solution. The DNA binding interaction with calf-thymus DNA (CT-DNA) was investigated by electronic absorption spectral titration and viscosity measurements. The results revealed that the phenanthroline complex (2) interact with CT-DNA through intercalation while bipyridyl complex (1) through the groove binding mode. The calculated intrinsic binding constant (K _b) of (1) and (2) were 0.5 and 4.4 × 10⁵ M^?1, respectively. Both the complexes were found to promote efficient DNA cleavage activities at low concentration in the presence of H₂O₂. The results showed that (2) has the highest DNA binding and nuclease activity. Furthermore, both the complexes were tested against human colon cancer (HCT 116) and breast cancer (MCF-7) cell lines and showed a dose-dependent antiproliferation effect.     

Left ventricular hypertrophy and chronic fluid overload in peritoneal dialysis patients

Purpose

Cardiovascular disease is the leading cause of mortality in dialysis patients with left ventricular hypertrophy (LVH) being an important predictor of mortality. We wanted to determine the prevalence of LVH in peritoneal dialysis (PD) patients and factors contributing to it.

Methods

This is a cross-sectional study assessing LVH using echocardiogram in PD patients. Left ventricular mass index (LVMI) was calculated to determine LVH. Chronic fluid overload (overhydration) was assessed using the body composition monitor, and blood pressure (BP) was measured using 24-h ambulatory BP monitoring.

Results

Thirty-one patients (21 females:10 males, 48.97 ± 14.50 years and dialysis vintage 40.0 ± 28.9 months) were studied. More than two-thirds (77.4 %) were hypertensive, and a third (35.5 %) were diabetic. Baseline data included mean serum albumin (37.34 ± 4.43 g/l), weekly Kt/V (2.02 ± 0.23), residual renal function of 68 (0–880) ml and ultrafiltration of 1,606.9 ± 548.6 ml. Majority of patients (80.6 %) had LVH on echocardiogram with LVMI of 136.5 ± 37.8 g/m² and overhydration of 2.23 ± 1.77 l. Average systolic BP, diastolic BP and mean arterial pressure were 141.2 ± 23.3, 90.8 ± 19.7 and 107.6 ± 19.6 mmHg, respectively. Patients with LVH had a lower serum albumin (p = 0.003), were more overhydrated (p = 0.010) and were on higher number of anti-hypertensive agents (p ≤ 0.001). Predictors of LVMI were overhydration (p = 0.002), the presence of diabetes (p = 0.008) and the number of anti-hypertensive agents used (p = 0.026). However, overhydration (p = 0.007) was the main predictor of LVH on multivariate analysis.

Conclusion

Overhydration is strongly associated with LVH in PD patients.     

Scorpion Toxin,BmP01, Induces Pain by Targeting TRPV1 Channel

The intense pain induced by scorpion sting is a frequent clinical manifestation. To date, there is no established protocol with significant efficacy to alleviate the pain induced by scorpion envenomation. One of the important reasons is that, little information on pain-inducing compound from scorpion venoms is available. Here, a pain-inducing peptide (BmP01) has been identified and characterized from the venoms of scorpion (Mesobuthus martensii). In an animal model, intraplantar injection of BmP01 in mouse hind paw showed significant acute pain in wild type (WT) mice but not in TRPV1 knock-out (TRPV1 KO) mice during 30 min recording. BmP01 evoked currents in WT dorsal root ganglion (DRG) neurons but had no effect on DRG neurons of TRPV1 KO mice. Furthermore, BmP01 evoked currents on TRPV1-expressed HEK293T cells, but not on HEK293T cells without TRPV1. These results suggest that (1) BmP01 is one of the pain-inducing agents in scorpion venoms; and (2) BmP01 induces pain by acting on TRPV1. To our knowledge, this is the first report about a scorpion toxin that produces pain by targeting TRPV1. Identification of a pain-inducing compound may facilitate treating pain induced by scorpion envenomation.     

Syntheses,Cholinesterases Inhibition,and Molecular Docking Studies of Pyrido[2,3‐b]pyrazine Derivatives

Cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), have a role in cholinergic deficit which evidently leads to Alzheimer's disease (AD). Inhibition of cholinesterases with small molecules is an attractive strategy in AD therapy. This study demonstrates synthesis of pyrido[2,3‐b]pyrazines ( 6a ‐ 6q ) series, their inhibitory activities against both cholinesterases, AChE and BChE, and molecular docking studies. The bioactivities data of pyrido[2,3‐b]pyrazines showed 3‐(3′‐nitrophenyl)pyrido[2,3‐b]pyrazine 6n a potent dual inhibitor among the series against both AChE and BChE with IC₅₀ values of 0.466 ± 0.121 and 1.89 ± 0.05 μm , respectively. The analogues 3‐(3′‐methylphenyl)pyrido[2,3‐b]pyrazine 6c and 3‐(3′‐fluorophenyl)pyrido[2,3‐b]pyrazine 6f were found to be selective inhibition for BChE with IC₅₀ values of 0.583 ± 0.052 μm and AChE with IC₅₀ value of 0.899 ± 0.10 μm , respectively. Molecular docking studies of the active compounds suggested the putative binding modes with cholinesterases. The potent compounds among the series could potentially serves as good leads for the development of new cholinesterase inhibitors.