Association between the polymorphisms of matrix metalloproteinases 9 and 3 genes and risk of myocardial infarction in Egyptian patients

Abstract The present study investigated the relationship between the genetic polymorphisms in MMP-9 and MMP-3 genes and acute myocardial infarction (AMI). We examined 40 patients with acute myocardial infarction and 40 age and sex matched controls for MMP-9 functional promoter polymorphism (1562 C > T) and MMP-3 (5A/6A) deletion/insertion polymorphism using restriction fragment length polymorphism (RFLP) for amplified genomic DNA. The frequencies of the combined mutant genotypes CT and TT in the (1562 C > T) MMP9 were significantly higher in AMI patients (20%) when compared to the controls (0%) (p value = 0.005) showing an association between these genotypes and AMI. Also there was a significant difference between 5A/5A genotype and 5A allele frequencies when both are compared in the patients (25% and 35%) and the controls (2.5% and 18.75%) (p= 0.009; OR =13; CI= 1.576–107.233); and (p=0.02; OR =2.333, CI= 1.130–4.820) respectively. In conclusion, the 1562C> T polymorphism of the MMP9 gene is strongly associated with acute myocardial infarction in the Egyptian population. Furthermore, our study supported the presence of the 5A/5A genotype of MMP3 gene promoter polymorphism as a risk factor of AMI in Egyptian patients. Meanwhile, the race selection should be paid more attention since the pathogenesis of a disease might have different bases in different racial population groups.Keywords: Matrix metalloproteinase; 1562C>T; 5A/6A; RFLP; Myocardial infarctionThe Egyptian Journal of Medical Human Genetics (2013) 14, 143–14

Echocardiographic Parameters of Severity in Isolated Neonatal Patent Ductus Arteriosus

Background: A hemodynamically-significant patent ductus arteriosus (hsPDA) compromises the early neonatal transition. There is no general agreement on echocardiographic indicators of hsPDA that can predict clinical decompensation. Aim of the Work: We aimed to assess echocardiographic parameters that are associated with the isolated PDA effects on hemodynamics, which could help in subsequent management decision making. Materials and Methods: We conducted a prospective observational analytical study on 50 neonates with isolated PDA and 20 controls. They underwent clinical and echocardiographic assessment at 48 hours of age, after another 48-72 hours and prior to discharge. Results: No correlation was found between PDA diameter and weight (p=0.72), length (p=0.11), Body surface area (BSA) (p=0.33), gestational age (p=0.13). A strong association of PDA-related hemodynamic instability was found with pulmonary hypertension (p=<0.01 & 0.05 for initial and latter studies). Left atrium diameter (LA) Z-score was higher among cases, correlated with PDA size in the 3 echocardiographic studies (p=0.001, 0.001 and 0.007 respectively), and correlated with hemodynamic instability in the initial study (p=0.03). Diameter of descending aorta at level of diaphragm and pulmonary flow/systemic flow ratio (Qp:Qs) correlated with PDA diameter in the latter 2 studies (p=0.001). Main pulmonary artery and left pulmonary artery (LPA) Z-scores were correlated with PDA size at the initial and follow-up studies as expected (p=0.001, 0.047 & 0.047; and p=0.004, 0.018 & 0.032, respectively). LPA Z-score correlated with hemodynamic instability at the follow-up study (p=0.005), which was not sustained at the subsequent study. Conclusion: Pulmonary hypertension, larger LA Z-score and LPA Z-scores are important early (at 48 hours) associations of a hsPDA and hemodynamic instability

Motesanib inhibits Kit mutations associated with gastrointestinal stromal tumors

<p>Abstract</p> <p>Background</p> <p>Activating mutations in Kit receptor tyrosine kinase or the related platelet-derived growth factor receptor (PDGFR) play an important role in the pathogenesis of gastrointestinal stromal tumors (GIST).</p> <p>Methods</p> <p>This study investigated the activity of motesanib, an inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3; PDGFR; and Kit, against primary activating Kit mutants and mutants associated with secondary resistance to imatinib. Single- and double-mutant isoforms of Kit were evaluated for their sensitivity to motesanib or imatinib in autophosphorylation assays and in Ba/F3 cell proliferation assays.</p> <p>Results</p> <p>Motesanib inhibited Kit autophosphorylation in CHO cell lines expressing primary activating mutations in exon 9 (AYins503-504, IC₅₀= 18 nM) and exon 11 (V560 D, IC₅₀= 5 nM; Δ552-559, IC₅₀= 1 nM). Motesanib also demonstrated activity against kinase domain mutations conferring imatinib resistance (V560D/V654A, IC₅₀= 77 nM; V560D/T670I, IC₅₀= 277 nM; Y823 D, IC₅₀= 64 nM) but failed to inhibit the imatinib-resistant D816V mutant (IC₅₀> 3000 nM). Motesanib suppressed the proliferation of Ba/F3 cells expressing Kit mutants with IC₅₀values in good agreement with those observed in the autophosphorylation assays.</p> <p>Conclusions</p> <p>In conclusion, our data suggest that motesanib possesses inhibitory activity against primary Kit mutations and some imatinib-resistant secondary mutations.</p

Progressive fibrosing interstitial lung diseases: current practice in diagnosis and management

Objective: Some patients with interstitial lung diseases (ILDs) other than idiopathic pulmonary fibrosis (IPF) develop a progressive fibrosing phenotype. We investigated the diagnosis and management of non-IPF ILDs using data from a survey of physicians and from US insurance claims. Methods: Pulmonologists, rheumatologists and internists in France, Germany, Italy, Japan, Spain, UK and US who had managed ≥10 patients with non-IPF ILDs in the past year, including those with progressive fibrosing ILDs, completed an online survey. Data on US insurance and prescription claims were obtained from a repository that aggregates data on claims routed from providers or pharmacies to payers. Results: In May–June 2017, 243 pulmonologists, 203 rheumatologists and 40 internists completed an online survey. Respondents estimated that 18–32% of patients diagnosed with non-IPF ILDs develop progressive fibrosis and that time from symptom onset to death in these patients was 61–80 months. Drug treatment was given to 50–75% of patients with non-IPF progressive fibrosing ILDs. Reasons for patients not being treated included that physicians considered patients to have mild or slowly progressing disease, or did not believe that available treatments are effective or well tolerated. Corticosteroids were the preferred first-line treatment for all types of non-IPF ILD. There was considerable heterogeneity in preferences for second- and third-line treatments. US insurance claims data from 3823 patients indicated that, in 2016, 50–75% of patients with ILDs received drug treatment (mostly corticosteroids) for their ILD. Conclusions: Physicians estimate that 18–32% of patients diagnosed with non-IPF ILDs develop a progressive fibrosing phenotype and that these patients experience significant delays in the diagnosis of ILD and the detection of progressive fibrosis. Between 25% and 50% of patients with progressive fibrosing ILDs do not receive drug therapy. There is an unmet need for effective and well tolerated treatments for progressive fibrosing ILDs

Microbial Status and Formation of Biogenic Amines in Salted Fish: A Study for Their Dietary Intake and Health Risk Assessment

Salted fish is a common food type in Egypt that is consumed in certain occasions and celebrations. The manufacture process of the salted fish allows fermentation of different fish species. Therefore, there is a high chance for microbial growth and multiplication on such rich protein substrate, and decomposition of the amino acids to their biogenic amines (BAs) derivatives. This study was undertaken to estimate the formed BAs in three salted fish retailed in Egypt, named feseikh, sahlia, and salted sardine. In addition, microbial counts including total plate counts (TPC), total psychrophilic counts (TPsC), and total Staphylococcus aureus counts (TSC) were enumerated. Dietary intakes and health risks associated with the formed BAs were also calculated and discussed. The obtained results revealed formation of the BAs in all examined salted fish species. Feseikh had the highest BAs contents as well as microbial counts. In conclusion, although the calculated dietary intakes revealed no potential risks associated with the consumption of the salted fish, however this assumption should be handled carefully due to inter-individual differences in their immune-reactions to such BAs, particularly histamine

Identification of sesquiterpene coumarins of oleo-gum resin of <i>Ferula assa-foetida</i> L. from the Yasuj region

<div><p>Chemical investigation of the oleo-gum resin of <i>Ferula assa-foetida</i> L. from Yasuj region led to the identification of five sesquiterpene coumarins namely, conferone (<b>1</b>), badrakemin (<b>2</b>), feslol (<b>3</b>), isosamarcandin (<b>4</b>) and samarcandin (<b>5</b>). The compounds were characterised by detailed 1D (¹H and ¹³C) and 2D NMR (HMBC, HSQC and NOESY) experiments. Among these compounds, conferone (<b>1</b>) and isosamarcandin (<b>4</b>) are being newly reported in <i>F. assa-foetida</i> L.</p></div

An Innovative Polymer-Based Electrochemical Sensor Encrusted with Tb Nanoparticles for the Detection of Favipiravir: A Potential Antiviral Drug for the Treatment of COVID-19

An innovative polymer-based electro-sensor decorated with Tb nanoparticles has been developed for the first time. The fabricated sensor was utilized for trace determination of favipiravir (FAV), a recently US FDA-approved antiviral drug for the treatment of COVID-19. Different techniques, including ultraviolet-visible spectrophotometry (UV-VIS), cyclic voltammetry (CV), scanning electron microscope (SEM), X-ray Diffraction (XRD) and electrochemical impedance spectroscopy (EIS), were applied for the characterization of the developed electrode TbNPs@ poly m-THB/PGE. Various experimental variables, including pH, potential range, polymer concentration, number of cycles, scan rate and deposition time, were optimized. Moreover, different voltammetric parameters were examined and optimized. The presented SWV method showed linearity over the range of 10-150 × 10-9 M with a good correlation coefficient (R = 0.9994), and the detection limit (LOD) reached 3.1 × 10-9 M. The proposed method was applied for the quantification of FAV in tablet dosage forms and in human plasma without any interference from complex matrices, obtaining good % recovery results (98.58-101.93%)