High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele

BACKGROUND: In-stent restenosis occurs in 10-30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. METHODS: In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. RESULTS: Average follow-up time was 1.0 (+ - 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ - 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. CONCLUSIONS: MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism

MR fluoroscopy in vascular and cardiac interventions (review)

Vascular and cardiac disease remains a leading cause of morbidity and mortality in developed and emerging countries. Vascular and cardiac interventions require extensive fluoroscopic guidance to navigate endovascular catheters. X-ray fluoroscopy is considered the current modality for real time imaging. It provides excellent spatial and temporal resolution, but is limited by exposure of patients and staff to ionizing radiation, poor soft tissue characterization and lack of quantitative physiologic information. MR fluoroscopy has been introduced with substantial progress during the last decade. Clinical and experimental studies performed under MR fluoroscopy have indicated the suitability of this modality for: delivery of ASD closure, aortic valves, and endovascular stents (aortic, carotid, iliac, renal arteries, inferior vena cava). It aids in performing ablation, creation of hepatic shunts and local delivery of therapies. Development of more MR compatible equipment and devices will widen the applications of MR-guided procedures. At post-intervention, MR imaging aids in assessing the efficacy of therapies, success of interventions. It also provides information on vascular flow and cardiac morphology, function, perfusion and viability. MR fluoroscopy has the potential to form the basis for minimally invasive image–guided surgeries that offer improved patient management and cost effectiveness

Design, synthesis and cytotoxic evaluation of a library of oxadiazole-containing hybrids

The development of hybrid compounds led to the discovery of new pharmacologically active agents for some of the most critical diseases, including cancer. Herein, we describe a new series of oxadiazole-containing structures designed by a molecular hybridization approach. Penicillin derivatives and amino acids were linked to amino acid and aromatic moieties through the formation of a 1,2,4-oxadiazole ring. Alternatively, condensation between amino acid-derived hydrazides and an activated penicillanic acid led to a series of 1,3,4-oxadiazole penicillin-containing hybrids and non-cyclized diacylhydrazides. From the cytotoxicity assays it is highlighted that two 1,2,4-oxadiazoles and one 1,3,4-oxadiazole connecting a penicillin and aliphatic amino acids displayed a high degree of cytotoxic selectivity, ranging between being three and four times more potent against tumor cells than normal cells. The results give a very interesting perspective suggesting that these hybrid compounds can offer a novel antitumor scaffold with promising cytotoxicity profiles.Fil: Camacho, Cristián Matías. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (CONICET-UNR); Argentina.Fil: Pizzio, Marianela G. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (CONICET-UNR); Argentina.Fil: Roces, David L. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (CONICET-UNR); Argentina.Fil: Boggian, Dora Bernarda. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (CONICET-UNR); Argentina.Fil: Mata, Ernesto Gabino. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario (CONICET-UNR); Argentina.Fil: Bellizzi, Yanina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas (UBA–CONICET); Argentina.Fil: Blank, Viviana C. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas (UBA–CONICET); Argentina.Fil: Roguin, Leonor P. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Fisicoquímica Biológicas (UBA–CONICET); Argentina

Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 to 2019.

AIMS: We report disease-specific cardiovascular causes of mortality amongst cancer patients in the USA between 1999 to 2019, considering temporal trends by age, sex, and cancer site. METHODS AND RESULTS: We used the Multiple Cause of Death database, accessed through the CDC WONDER (Centres for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) resource. We included 629,308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with largest change in breast cancer patients (+191.1%). CONCLUSIONS: We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high cardiovascular risk population