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IntroductionDiabetic cardiomyopathy (DCM) is a serious complication that frequently occurs in patients with type 1 diabetes (T1D) necessitating early diagnosis. The aim of the current study was to detect subclinical DCM in Egyptian children and adolescents with T1D and evaluate the effect of antioxidants on myocardial dysfunction.Material and methodsThe current prospective observational cohort study included 81 T1D patients (9-20 years old) with diabetes duration > 4 years compared to 50 age and sex matched non-diabetic controls. Serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was assessed in addition to conventional echocardiography, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE). Patients with myocardial dysfunction were supplemented with vitamin E (α-tocopherol) as an antioxidant for 1 year, then follow up echocardiography was done.ResultsNT-proBNP was elevated in 73 (90.1%) patients, 50.6% had left ventricular (LV) diastolic dysfunction, 14.8% had right ventricular (RV) diastolic dysfunction, 84% had LV systolic dysfunction and 91.4% had RV systolic dysfunction with statistically significant difference compared to controls. There was a significant negative correlation between LV global longitudinal strain (GLS) and NT-proBNP (pConclusionsNT-proBNP and non-conventional echocardiography were useful in early detection of subclinical cardiomyopathy in patients with T1D. Antioxidant treatment improved subclinical myocardial dysfunction in T1D patients.

BackgroundTetralogy of Fallot (TOF) is a common congenital cyanotic heart disease in which arrhythmias could develop even after successful operative repair. Pulmonary regurgitation and right ventricular dilatation develop in many cases. The relation between arrhythmias and right ventricular dilatation is not established. Our aim is to assess the relation in between the degree of right ventricular volume affection and the severity of the pulmonary regurgitation, associated arrhythmias and the need for pulmonary valve repair in Egyptian pediatric and adolescent cases after successful TOF repair.ResultsA cross sectional descriptive study was conducted on 32 cases after successful surgical repair. Transthoracic Doppler echocardiography, 24 h Holter monitoring and cardiac MRI for assessment of pulmonary regurgitation fraction (PRF), ventricular volumes and function were measured. Cases were classified according to right ventricular end diastolic volume index (RVEDVI) into 2 groups with cut off value 150 ml/m2. Mean age of the studied cases was (12.96 ± 3.384) years, mean age at time of surgical repair was (34.23 ± 22.1) months, and mean duration postoperatively was (121.72 ± 41.028) months. Eighteen cases (56%) had RVEDVI ≥ 150 ml/m2, PRF was significantly higher in cases with increased RVEDVI (pvalue 0.007), with positive significant correlation between RVEDVI and PRF (pvalue = 0.0001,r = 0.61). Arrhythmias were detected in 18 cases (56%), the most common of which was infrequent supraventricular ectopy. No significant difference in incidence of arrhythmias between the 2 groups (pvalue = 1) with also no significant correlation between arrhythmias and increased RVEDVI (pvalue = 0.76,r = 0.05). No difference between cases with and without arrhythmias regarding RVEDVI (pvalue = 0.56) or PRF (pvalue = 0.5).ConclusionHolter detected arrhythmias after successful surgical repair of TOF were significantly associated with increased postoperative duration but not with PRF or RVEDVI.

Exaggerated inflammatory responses may cause serious and debilitating diseases such as acute lung injury and rheumatoid arthritis. Two series of chalcone derivatives were prepared as anti-inflammatory agents. Methoxylated phenyl-based chalcones 2a-l and coumarin-based chalcones 3a-f were synthesized and compared for their inhibition of COX-2 enzyme and nitric oxide production suppression. Methoxylated phenyl-based chalcones showed better inhibition to COX-2 enzyme and nitric oxide suppression than the coumarin-based chalcones. Among the 18 synthesized chalcone derivatives, compound 2f exhibited the highest anti-inflammatory activity by inhibition of nitric oxide concentration in LPS-induced RAW264.7 macrophages (IC50 = 11.2 μM). The tested compound 2f showed suppression of iNOS and COX-2 enzymes. Moreover, compound 2f decreases in the expression of NF-κB and phosphorylated IκB in LPS-stimulated macrophages. Finally, docking studies suggested the inhibition of IKKβ as a mechanism of action and highlighted the importance of 2f hydrophobic interactions.

Uncontrolled type-1 diabetes (T1DM) can lead to dyslipidaemia and albuminuria, which may promote cardiovascular injuries. However, some lipidemic factors could be useful in predicting cardiac dysfunction. Seventy-eight adolescents under insulin treatment due to a 6-year history of T1DM and were retrospectively examined. Glycemia, lipidemia, and albuminuria were measured in addition to development of cardiovascular abnormalities Both girls and boys showed higher HbA1c and fasting blood glucose and 27.1% females and 33.3% males exhibited microalbuminuria though their plasma levels of total cholesterol (TC), triglycerides (TG), and low-density lipoproteins (LDL) and high-density lipoproteins (HDL lipoproteins were in the normal range. They exhibited a preserved systolic function, but 50% of females and 66.6% of males had developed diastolic failures. Interestingly, girls with diastolic dysfunction showed significantly lower concentrations of HDL and higher TC/HDL and TG/HDL ratios. In fact, low HDL levels (OR 0.93, 95% CI 0.88&ndash, 0.99, p = 0.029) and high TC/HDL (OR 2.55, 95% CI 1.9&ndash, 5.45, p = 0.016) and TG/HDL (OR 2.74, 95% CI 1.12&ndash, 6.71, p = 0.028) ratios associated with the development of diastolic complications. The cut-off values for HDL, TC/HDL, and TG/HDL were 49 mg/dL, 3.0 and 1.85, respectively. HDL and TC/HDL and TG/HDL ratios may be useful for predicting diastolic dysfunction in girls with uncontrolled T1DM.

IntroductionA role for ficolin (FCN) 2 gene polymorphisms in the pathogenesis of recurrent severe streptococcal infections and rheumatic carditis has been suggested. The aim of the study was to evaluate a possible relationship between single nucleotide polymorphisms located at positions -602 and -4 of the FCN2 gene and FCN2 serum levels and risk of development of rheumatic fever (RF) and rheumatic heart disease (RHD).Material and methodsSeventy-seven Caucasian Egyptian patients with RF were recruited with a control group of 43 healthy subjects. DNA was extracted for analysis of the FCN2 gene at positions -602 and -4 and serum protein level was measured by ELISA.ResultsFCN2 AA genotype at the -4 position was more frequently observed in RF and RHD patients, as compared to healthy subjects (p = 0.005 and p = 0.013, respectively); furthermore, the A allele was identified as a possible risk factor for the development of RF (p = 0.023, OR = 1.852, 95% CI: 1.085–3.159). The haplotype –602/–4 G/A, which was associated with low median levels of L-ficolin, was observed more frequently in the RF group when compared to the healthy subjects (74/162, 48.1% vs. 29/420, 33.7%, OR = 1.834, 95% CI: 1·034–3.252, p = 0·038). Low serum ficolin 2 level was associated with ESV and EDV increases. FCN 2 level was significantly lower with AA genotypes than GG+AG genotypes of the -4 position (56.68 ±17.90 vs. 66.05 ±18.79, p = 0.008).ConclusionsPolymorphisms linked to low levels of L-ficolin may render an individual at risk of recurrent and/or severe streptococcal infection. The -4 AA genotype and -602/-4 G/A haplotype are possible risk factors for the development of carditis.

Two series of pyrazoline compounds were designed and synthesized as antiproliferative agents by VEGFR pathway inhibition. All synthesized compounds were screened by the National Cancer Institute (NCI), Bethesda, USA for anticancer activity against 60 human cancer cell lines. Compound 3f exhibited the highest anticancer activity on the ovarian cell line (OVCAR-4) with IC50 = 0.29 μM and on the breast cell line (MDA-MB-468) with IC50 = 0.35 μM. It also exhibited the highest selectivity index (SI = 74). Compound 3f caused cell cycle arrest in OVCAR-4 cell line at the S phase which consequently inhibited cell proliferation and induced apoptosis. Moreover, 3f showed potent down-regulation of VEGF and p-VEGFR-2. Docking studies showed that compound 3f interacts in a similar pattern to axitinib on the VEGFR-2 receptor. The same compound was also able to fit into the gorge of STAT3 binding site, the transcription factor for VEGF, which explains the VEGF down-regulation.

A series of pyrazoline derivatives 2a-e, 3a-e and 4a-e structurally related to combretastatin A4 (CA-4) were synthesized and characterized by spectroscopic means and elemental analyses. In these compounds, the cis double bond of CA-4 was replaced with the pyrazoline ring aiming to enhance the cytotoxic effects displayed by CA-4 and to prevent the cis/trans isomerization that is associated with inactivation of CA-4. The cytotoxic activity of all new compounds was investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by the most active compounds 3d, 4a and e was evaluated. The cytotoxicity of 4e was correlated with induction of apoptosis and caspase-3 activation in vitro thus indicating the apoptotic pathway of anticancer effect of these compounds. Furthermore, in vivo evaluation of the synthesized compounds was carried out against Ehrlich's ascites carcinoma (EAC) solid tumor grown in mice. Compounds 2c, 3a and e showed significant reduction in tumor weight, and about 2-4 fold increase in caspase-3 expression.

Background and objectives To evaluate the efficacy of recently updated Jones criteria for diagnosis of rheumatic fever in high incidence populations like Egypt. Methods Clinical data of 891 Egyptian patients with rheumatic fever, aged 5-15 years in a highly specialized rheumatic fever clinic were reviewed retrospectively from March 2014 to March 2016. Discriminant analysis was used to detect the most effective predictors for diagnosis of rheumatic fever in our patients incorporating echocardiographic criteria. We compared our results to the most recent update by the American Heart Association. Results The most effective predictors of rheumatic fever included arthritis, carditis, chorea, aortic regurgitation, grades of mitral regurgitation ≥10mm length and velocity ≥2.5 m/s, thick anterior mitral valve leaflets, elevated acute phase reactants, positive family history and prolonged PR interval. Our predictors showed a high sensitivity of 93%, a specificity of 62% and an overall prediction accuracy of 81.4%. Conclusion We concluded that strict application of updated Jones criteria may lead to under diagnosis of rheumatic fever in highly endemic countries. We recommend further studies to examine the sensitivity of the most recent update of Jones criteria on other highly endemic populations.

Various 1,3,4-oxadiazole-2-thiol derivatives have considerable potential in the field of antitumor activity. On the basis of the structure of the highly active reported oxadiazole analogues, 36 novel compounds were designed. Their molecular transport properties were predicted using a computer-aided program, and they were then synthesized and tested for anticancer activity against the breast cancer cell line MCF-7. Most of the tested compounds showed excellent to potent cytotoxic activity. Docking studies were carried out to examine the possibilities of the target compounds to become lead compounds in the future after more biological investigations. Compounds 18 and 22 were more active than the reference drug with IC₅₀ values of 0.010 µM and 0.012 µM, respectively, and binding energy scores of -10.32 and -10.25, respectively.

A series of new pyridine derivatives 4a-c, 5a-d, 6a-d, 7a-f, and 8a-f structurally related to ABT-751 were synthesized and characterized by spectroscopic means and elemental analysis. All the synthesized compounds were tested for their cytotoxic activity in vitro against the HCT-116 and HepG-2 cancer cell lines using the MTT assay. The results showed that compound 8d has higher cytotoxic activity than the reference antimitotic agent colchicine, against both tested cell lines, with IC50 = 0.52 and 1.40 μM, respectively. The three most active compounds, 5d, 8b, and 8d, were further screened in vitro for inhibition of tubulin and showed remarkable results in comparison to colchicine.

Background: Primary prevention of acute rheumatic fever is achieved by proper antibiotic treatment of group A β -hemolytic streptococcal (GAS) pharyngitis. Methods: To assess noninferiority of oral amoxicillin to intramuscular benzathine penicillin G (IM BPG). Children (2 to 12 years) meeting enrollment criteria were randomized 1:1 to receive antibiotic treatment in 2 urban outpatient clinics in Egypt and Croatia. Results: A total of 558 children (Croatia = 166, Egypt = 392) were randomized, with 368 evaluable in an intention-to-treat (ITT) analysis, and 272 evaluable in the per protocol (PP) analysis. In Croatia, ITT and PP treatment success rates were comparable for IM BPG and amoxicillin (2.5% difference vs 1.1% difference, respectively). In Egypt, amoxicillin was not comparable with IM BPG in ITT analysis (15.1% difference), but was comparable in PP analysis (-9.3% difference). Conclusion: If compliance is a major issue, a single dose of IM BPG may be preferable for treatment of GAS pharyngitis.