Green Synthesis of Highly Fluorescent Carbon Dots from Bovine Serum Albumin for Linezolid Drug Delivery as Potential Wound Healing Biomaterial: Bio-Synergistic Approach, Antibacterial Activity, and In Vitro and Ex Vivo Evaluation.

A simple and green approach was developed to produce novel highly fluorescent bovine serum albumin carbon dots (BCDs) via facile one-step hydrothermal treatment, using bovine serum albumin as a precursor carbon source. Inherent blue photoluminescence of the synthesized BCDs provided a maximum photostability of 90.5 ± 1.2% and was characterized via TEM, FT-IR, XPS, XRD, UV-visible, and zeta potential analyses. By virtue of their extremely small size, intrinsic optical and photoluminescence properties, superior photostability, and useful non-covalent interactions with the synthetic oxazolidinone antibiotic linezolid (LNZ), BCDs were investigated as fluorescent nano-biocarriers for LNZ drug delivery. The release profile of LNZ from the drug delivery system (LNZ-BCDs) revealed a distinct biphasic release, which is beneficial for mollifying the lethal incidents associated with wound infection. The effective wound healing performance of the developed LNZ-BCDs were evaluated through various in vitro and ex vivo assays such as MTT, ex vivo hemolysis, in vitro antibacterial activity, in vitro skin-related enzyme inhibition, and scratch wound healing assays. The examination of LNZ-BCDs as an efficient wound healing biomaterial illustrated excellent biocompatibility and low cytotoxicity against normal human skin fibroblast (HSF) cell line, indicating distinct antibacterial activity against the most common wound infectious pathogens including Staphylococcus aureus (ATCC® 25922) and methicillin-resistant Staphylococcus aureus, robust anti-elastase, anti-collagenase, and anti-tyrosinase activities, and enhanced cell proliferation and migration effect. The obtained results confirmed the feasibility of using the newly designed fluorescent LNZ-BCDs nano-bioconjugate as a unique antibacterial biomaterial for effective wound healing and tissue regeneration. Besides, the greenly synthesized BCDs could be considered as a great potential substitute for toxic nanoparticles in biomedical applications due to their biocompatibility and intense fluorescence characteristics and in pharmaceutical industries as promising drug delivery nano-biocarriers for effective wound healing applications.

Contribution of glutathione peroxidase 1 (Pro200Leu) single nucleotide polymorphism and serum homocysteine levels in the risk of acute myocardial infarction in Egyptians.

BACKGROUND: Oxidative stress is among the most common risk factors in the pathogenesis of acute myocardial infarction (AMI). Glutathione peroxidase 1 enzyme coded by the GPX1 gene plays an essential role in reducing oxidative stress. Previous studies correlated the GPX1 (Pro200Leu) single nucleotide polymorphism (SNP) with AMI incidence. Elevated homocysteine (Hcy) levels induce oxidative stress and are considered an independent risk factor for AMI. Evidence showed a complex relationship between Hcy and GPx-1 activity. This study examined the association of the common (Pro200Leu) SNP in GPX1 with AMI incidence in an Egyptian population. This study is the first to check this association in an Egyptian population. Moreover, the association between serum Hcy and the incidence of AMI was checked, and the novelty was to statistically correlate GPX1 Pro200Leu genotypes with serum Hcy levels in patients and control subjects. Hundred control subjects and hundred and twenty AMI patients were genotyped using PCR-RFLP analysis. An ELISA was used to measure serum Hcy levels. RESULTS: The GPX1 (Pro200Leu) genotype distribution and allele frequency were not significantly different between patients and control subjects (P = 0.60 and P = 0.62, respectively). Serum levels of Hcy were significantly elevated in patients compared to control subjects (P ≤ 0.0001). However, no significant difference was observed in serum Hcy levels among different GPX1 genotypes in neither patients nor control subjects. CONCLUSIONS: The minor T allele of GPX1 Pro200Leu is not associated with AMI risk in this Egyptian population. However, high homocysteine serum levels might contribute independently to the risk of AMI. Finally, Hcy levels were not significantly different in homozygous minor TT compared to homozygous wild CC.

Non-polar metabolites of green beans (Phaseolus vulgaris L.) potentiate the antidiabetic activity of mesenchymal stem cells in streptozotocin-induced diabetes in rats.

Green beans (Phaseolus vulgaris L.) are consumed as pods or mature seeds (common beans). The pods were extracted with 95% ethanol and processed to prepare non-polar and polar fractions. Comparing the antihyperglycemic activity of both fractions, non-polar fraction (NPF, 200 mg kg-1  day-1 ) lowered blood glucose in streptozotocin diabetic rats by 65% compared to 57% for the polar fraction at the same dose. When NPF treatment was combined with injection of mesenchymal stem cells (MSC) a 4.4-fold increase in serum insulin and a 73.6% reduction in blood glucose were observed compared to untreated control. Additionally, a significant decrease in malondialdehyde (76.2%), nitric oxide (68.2%), cholesterol (76.1%), and triglycerides (69.5%) and a 1.75-fold increase in HDL concentrations were observed in the group treated with this combination compared to diabetic animals. Interestingly, NPF increased homing of MSC in pancreas potentiating their antidiabetic activity. Finally, 26 compounds were identified in NPF using LC/MS analysis and four were isolated in pure form. The isolated compounds namely calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol showed good inhibitory activity against pancreatic lipase with IC50 at 1.93, 1.07, 1.34 and 1.44-1 µg/ml, respectively. Additionally, these compounds inhibited α-amylase, albeit at higher concentration, with IC50 at 248, 212, 254, and 155 µg/ml for calotroproceryl acetate, fridelin, calotroproceryl A, and stigmasterol, respectively. Our results suggest that green beans extract can potentiate effect of MSC in diabetes directly due to its own antidiabetic effect and indirectly by increasing MSC homing in pancreatic tissues. PRACTICAL APPLICATIONS: It has been suggested in this study that green beans can improve hyperglycemia, oxidative balance in diabetes, so green beans can be promoted as a healthy nutrient for diabetic patients. Green beans also can enhance homing and differentiation of mesnchymal stem cells in the pancreas for future stem cell therapy of type I diabetes.

Is there a correlation between -174(G/C) polymorphism of IL-6 gene and the incidence of acute myocardial infarction?

BACKGROUND: Cardiovascular disease (CVD) remains the major cause of death worldwide. Most CVD can be prevented by addressing risk factors. Acute myocardial infarction (AMI) is an inflammatory disorder characterized by changes in several cytokines including the interleukins (ILs). Studies are running to evaluate the genetic variation in the inflammatory system and their influence on the risk factors for CVD aiming for future prevention of this global disease. The aim of the current study was too investigate the association of -174 (G/C) IL-6 polymorphism with the incidence of AMI in a representative sector of the Egyptian population and to examine the contribution of IL-6, as a biomarker, in the pathogenesis of AMI. Genotyping of -174 (G/C) IL-6 polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) while IL-6 levels were assayed by ELISA. RESULTS: The genotype distribution of -174 (G/C) IL-6 gene was not significantly different between the control subjects (GG 81.7%, GC 16.3%, CC 1.9%) and the AMI patients (GG 79%, GC 19%, CC 2%).The serum levels of IL-6 were significantly elevated in the AMI patients in comparison to the control subjects (P < 0.0001). CONCLUSIONS: There is no significant association of -174(G/C) polymorphism in the promoter sequence of IL-6 and the incidence of AMI in the examined sample of Egyptian population. Elevated levels of serum IL-6 confirmed the relationship between inflammation and the incidence of AMI.

Molecular Networking Leveraging the Secondary Metabolomes Space of Halophila stipulaceae (Forsk.) Aschers. and Thalassia hemprichii (Ehrenb. ex Solms) Asch. in Tandem with Their Chemosystematics and Antidiabetic Potentials.

The Red Sea is one of the most biodiverse aquatic ecosystems. Notably, seagrasses possess a crucial ecological significance. Among them are the two taxa Halophila stipulacea (Forsk.) Aschers., and Thalassia hemprichii (Ehrenb. ex Solms) Asch., which were formally ranked together with the genus Enhalus in three separate families. Nevertheless, they have been recently classified as three subfamilies within Hydrocharitaceae. The interest of this study is to explore their metabolic profiles through ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS/MS) analysis in synergism with molecular networking and to assess their chemosystematics relationship. A total of 144 metabolites were annotated, encompassing phenolic acids, flavonoids, terpenoids, and lipids. Furthermore, three new phenolic acids; methoxy benzoic acid-O-sulphate (16), O-caffeoyl-O-hydroxyl dimethoxy benzoyl tartaric acid (26), dimethoxy benzoic acid-O-sulphate (30), a new flavanone glycoside; hexahydroxy-monomethoxy flavanone-O-glucoside (28), and a new steviol glycoside; rebaudioside-O-acetate (96) were tentatively described. Additionally, the evaluation of the antidiabetic potential of both taxa displayed an inherited higher activity of H. stipulaceae in alleviating the oxidative stress and dyslipidemia associated with diabetes. Hence, the current research significantly suggested Halophila, Thalassia, and Enhalus categorization in three different taxonomic ranks based on their intergeneric and interspecific relationship among them and supported the consideration of seagrasses in natural antidiabetic studies.

The association of megalin and cubilin genetic variants with serum levels of 25-hydroxvitamin D and the incidence of acute coronary syndrome in Egyptians: A case control study.

Megalin and cubilin are two receptors that mediate endocytosis of 25-hydroxyvitamin D (25(OH)D) for its final activation by hydroxylation. The aim of the present study was to evaluate the association of polymorphisms in megalin (rs2075252 and rs4668123) and cubilin (rs1801222 and rs12766939) with the circulating serum levels of 25(OH)D and with the early incidence of acute coronary syndrome (ACS) in Egyptians. The study included 328 subjects; 185 ACS patients aged between 27 and 60 years, and 143 healthy age-matched controls. Genotyping of cubilin rs12766939 Single Nucleotide Polymorphism (SNP) was performed using Real-Time Polymerase Chain Reaction (qPCR) and for megalin rs4668123 and rs2075252 and cubilin rs1801222 by Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP). 25(OH)D levels were measured by Ultra Performance Liquid Chromatography- Tandem Mass Spectroscopy (UPLC-MS/MS). Results showed that vitamin D deficiency was highly linked to ACS incidence (P < 0.0001). The megalin rs4668123 CC, cubilin rs1801222 GG and cubilin rs12766939 GG + GA genotypes are associated with a higher ACS incidence and can be considered risk factors, according to Chi-squared test (P = 0.0003, 0.0442, 0.013 respectively). Conversely, the megalin rs2075252 SNP was not associated with increased ACS incidence. However, after performing multiple logistic regression analysis, only the megalin rs4668123 SNP was considered an independent ACS risk factor. Furthermore, the megalin rs4668123 CC genotype was associated with lower 25(OH)D levels (P = 0.0018). In conclusion, megalin rs4668123 (CC) was linked to lower 25(OH)D levels and can be considered an independent risk factor for incidence of ACS.

The Association of Fractalkine Receptor (T280M) Polymorphism in the Pathogenesis of Acute Coronary Syndrome in the Egyptian Population.

BACKGROUND: Fractalkine (FKN) in its free and membrane bound-forms and its receptor CX3CR1are reported to have an atherosclerotic effect. The relationship of Single Nucleotide Polymorphisms (SNPs) in FKN and CX3CR1genes with the Coronary Artery Disease (CAD) risk showed conflicting results in different populations. The aim of this study was to investigate the influence of CX3CR1 threonine 280 methionine (T280M) polymorphism in the predisposition of Acute Coronary Syndrome (ACS) in Egyptians. METHODS: 200 Egyptian subjects were recruited for the study. They were divided into 100 ACS patients and 100 healthy controls. Genotyping of CX3CR1 T280M was performed using a Polymerase Chain Reaction-restriction Fragment Length Polymorphism (PCR-RFLP). Serum FKN was assayed by Enzyme - Linked - Immuno- Sorbent-Assay (ELISA). RESULTS: T and M allele frequencies for CX3CR1gene were not significantly different between ACS and Controls (p=0.76). Moreover, none of the genotypes had an atheroprotective effect. Serum analysis showed higher levels of FKN in ACS patients (p=0.041). FKN levels were not significantly different among genotypes of control and ACS groups (p=0.34) and (p=0.38) respectively. CONCLUSION: This study shows that CX3CR1 T280M polymorphism does not affect the incidence of ACS the Egyptian population. Moreover, none of the genotypes were associated with higher FKN levels.

AGXT2 and DDAH-1 genetic variants are highly correlated with serum ADMA and SDMA levels and with incidence of coronary artery disease in Egyptians.

Dimethylarginine aminodehydrolase (DDAH1) and alanine glyoxylate aminotransferase2 (AGXT2) are two enzymes that contribute in asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) metabolism. Hence they affect production and bioavailability of eNOS-derived nitric oxide (NO) and consequently healthy blood vessels. The major aims of the current study were to investigate the association of genetic variants of AGXT2 rs37369, AGXT2 rs16899974 and DDAH1 rs997251 SNPs with incidence of coronary artery disease (CAD) in Egyptians and to correlate these variants with the serum levels of ADMA and SDMA. The study included 150 subjects; 100 CAD patients and 50 healthy controls. Genotyping was performed by qPCR while the ADMA and SDMA concentrations were assayed by ELISA. Both serum ADMA and SDMA concentrations were significantly higher in CAD patients compared to controls (both p < 0.0001). Genotype distributions for all studied SNPs were significantly different between CAD patients and controls. Carriers of AGXT2 rs37369-T allele (CT + TT genotypes) and AGXT2 rs16899974-A allele (CA + AA genotypes) had 2.4- and 2.08-fold higher risk of having CAD than CC genotype in both SNPs (p = 0.0050 and 0.0192, respectively). DDAH1 rs997251 TC + CC genotypes were associated with 2.3-fold higher risk of CAD than TT genotype (p = 0.0063). Moreover, the AGXT2 rs37369 TT and AGXT2 rs16899974 AA genotypes were associated with the highest serum ADMA and SDMA while DDAH1 rs997251 CC genotype was associated with the highest ADMA. AGXT2 rs37369-T, AGXT2 rs16899974-A, and DDAH1 rs997251-C alleles represent independent risk factors for CAD in the Egyptians.

C(-260)T Polymorphism in CD14 Receptor Gene of Egyptians with Acute Myocardial Infarction.

BACKGROUND: Despite the significance of the traditional risk factors, recently published studies have suggested that inflammatory processes and variations in the genetics of the inflammatory system may participate in the initiation of atherosclerosis and its complications. OBJECTIVE: To investigate the possible association between CD14 C(-260)T (rs2569190) gene polymorphism and the risk of acute myocardial infarction in the Egyptian population. METHODS: We enrolled 100 acute myocardial infarction patients in addition to 107 healthy controls. Deoxyribonucleic acid was extracted, purified and used for the genotype assay of C(-260)T polymorphism in promoter region of CD14 gene. Genotyping was conducted using polymerase chain reactionrestriction fragment length polymorphism. Polymerase chain reaction product was digested using a restriction enzyme and the digestion products were specified. Serum CD14 levels were determined by Enzyme Linked Immunosorbent Assay. RESULTS: CD14 genotypic distribution (CC: 15.9% vs. 16%, CT: 62.6% vs. 58%, TT: 21.5% vs. 26% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) and allele frequencies (C allele: 47% vs., 45%, T allele: 52% vs. 55% in controls versus acute myocardial infarction patients, p > 0.05 for all variables) did not show a statistical significant difference. Serum CD14 levels were elevated in acute myocardial infarction patients (5.73±0.62 vs. 4.48±0.28 pg/ml, p < 0.05). However, there was no statistically significant difference in serum CD14 levels among different CD14 genotypes. CONCLUSION: CD14 C-(260)T polymorphism is not associated with incidence of acute myocardial infarction in Egyptians who showed elevated serum CD14 levels in comparison to healthy individuals.

Genetic Variants of CYP2R1 Are Key Regulators of Serum Vitamin D Levels and Incidence of Myocardial Infarction in Middle-Aged Egyptians.

BACKGROUND: Myocardial Infarction (MI) is one of the leading causes of morbidity and mortality in Egypt and worldwide. Vitamin D deficiency has long been linked to incidence of cardiovascular diseases. Several factors were reported to contribute to serum vitamin D level including exposure to sunlight. However, genetic variations in the vitamin D metabolic pathways have also been considered as strong determinants of vitamin D levels. CYP2R1 is the major 25-hydroxylase enzyme that is responsible for the 1st activation step of vitamin D. OBJECTIVE: to investigate the contribution of polymorphisms in CYP2R1 gene to vitamin D deficiency and incidence of MI in Egyptians. METHODS: The study included 323 subjects; 185 MI patients and 138 healthy controls. Serum 25OHD3, 25OHD2 and total 25OHD levels were measured using LC-MS/MS. SNPs rs2060793 and rs1993116 were determined by polymerase chain reaction - restriction fragment length polymorphism (PCRRFLP) which is considered one of the most commonly used techniques in genotyping. SNP rs10766197 was detected using TaqMan allele discrimination assay. RESULTS: Serum 25OHD3, 25OHD2 and total 25OHD levels were found to be significantly lower in MI patients than controls. The three studied SNPs were associated with significantly different total 25OHD levels and their genotype distributions differed significantly between MI patients and controls where the high risk genotypes were AG/AA for rs2060793, AG/GG for rs1993116 and AG/AA for rs10766197. Additionally, the concurrent presence of high risk genotypes of the three studied SNPs rendered those individuals at extremely higher risk for MI than each individual SNP (OR 14.1, 95% CI (3.1-64.7), p-value = < 0.0001). CONCLUSIONS: Genetic variants of CYP2R1 are key determinants of serum 25OHD levels and are highly associated with MI risk.

Polymorphisms in Gap Junction Proteins and their Role in Predisposition of Acute Myocardial Infarction in Egyptians.

BACKGROUND: Connexin (Cx) proteins are the building blocks of gap junctions. Among these, Cx37 and Cx40 are expressed on vascular system and reported to have cardioprotective role. Linking polymorphisms in genes coding for Cx and coronary artery disease (CAD) risk showed conflicting results in different populations. None has been studied before in Egyptians. Therefore, the aims of this study were to investigate the influence of Cx37 C1019T and Cx40 A71G polymorphisms on the predisposition of acute myocardial infarction (AMI) in Egyptians, to study linkage disequilibrium (LD) and combined effects of single nucleotide polymorphisms (SNPs) and to correlate the genotypes with sVCAM-1 serum levels. METHODS: Total of 201 Egyptian subjects were recruited for the study. They were divided into 104 AMI patients and 97 healthy controls. Genotypes for each participant were determined using a polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum sVCAM-1was measured by ELISA. RESULTS: Allele frequencies for both Cx37 and Cx40 were not significantly different between AMI and Controls (p=0.93 and p=0.26 respectively). Moreover, studying the dominant and recessive models concluded that none of the genotypes was a risk factor. Both SNPs were not in LD (R2=0.0027). Serum analysis showed higher levels of sVCAM-1 in AMI patients (p<0.0001). sVCAM-1 levels were not significantly different among SNPs (Cx37; p=0.244 and Cx40; p=0.266). CONCLUSION: This study shows that Cx37 C1019T and Cx40 A71G polymorphisms are not associated with cardioprotective role in Egyptians. Moreover, both SNPs are inherited separately and none of the genotypes were associated with higher sVCAM-1 levels.

The Role of Nitric Oxide from Neurological Disease to Cancer.

Until the beginning of the 1980s, nitric oxide (NO) was just a toxic molecule of a lengthy list of environmental pollutants such as cigarette smoke and smog. In fact, NO had a very bad reputation of being destroyer of ozone, suspected carcinogen and precursor of acid rain. However, by the early 1990s it was well recognized by the medical research community. Over the last two decades, the picture has been totally changed. Diverse lines of evidence have converged to show that this sometime poison is a fundamental player in the everyday business of the human body. NO activity was probed in the brain, arteries, immune system, liver, pancreas, uterus, peripheral nerves, lungs, and almost every system in the human body. NO is a major player in the cardiovascular system as it is involved in regulating blood pressure. In the CNS, it is involved in memory formation and the regulation of cerebral blood flow to ensure adequate supply of blood to the brain. Because NO is involved in many pathways, it has a role in several diseases related to modern life as hypertension, coronary heart diseases, Alzheimer's Disease, stroke and cancer. This chapter focuses on the discussion of the role of NO in neurological diseases and cancer and how can this Janus-faced molecule play a role in the pathology and personalized treatment of these diseases.

Association of manganese superoxide dismutase Ala16Val polymorphism in the incidence of acute myocardial infarction in the Egyptians.

Background: Oxidative stress has been implicated in various diseases including atherosclerosis; the most common pathologic process underlying acute myocardial infarction (AMI). The manganese superoxide dismutase (MnSOD) antioxidant enzyme affords the major defense against reactive oxygen species (ROS) within the mitochondria. MnSOD Alanine16Valine (A16V) single nucleotide polymorphism (SNP) has been shown to decrease MnSOD detoxification activity. Aim: A case-control study was conducted to investigate the association between MnSOD A16V polymorphism and the incidence of AMI in the Egyptians, investigate the contribution of oxidative stress represented by hexanoyl lysine adduct (HEL), an oxidative stress biomarker, in the pathogenesis of AMI and finally correlate the MnSOD genotypes with HEL serum levels. Methods: A total of 200 Egyptian subjects were recruited for the study; 100 AMI patients and 100 control subjects. Genotypes of the MnSOD A16V polymorphism were determined using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum HEL was measured by ELISA. Results: A significant difference in the distribution of the MnSOD A16V genotypes was observed; VV genotype was significantly higher in AMI than controls (p ≤ 0.0001). Also, studying the allele frequencies revealed that Val allele was significantly higher in AMI than controls (p ≤ 0.0001). Serum analysis showed higher levels of HEL in AMI patients (p = 0.0142). Furthermore, HEL levels were found to be significantly higher in VV genotype in AMI (p = 0.0273). Conclusions: Our study suggests that MnSOD A16V polymorphism is associated with increased risk of developing AMI in the Egyptians. Moreover, the VV genotype is associated with higher HEL levels.

Assessment of the link between endothelin K198n Snp, endothelin concentration and acute myocardial infarction in Egyptians.

The aim of the current study was to assess the link between EDN K198N SNP, ET-1 serum concentration and acute myocardial infarction (AMI) in Egyptians. The study cohort consisted of 84 patients at AMI onset and 84 age-matched healthy controls. Endothelin genotypes and concentrations were determined by sequencing and ELISA, respectively. Genotype distribution was not significantly different between AMI patients and controls (P=.8341). The mean serum ET-1 concentration of patients (13.83±0.7 pg/mL) was significantly higher than controls (7.26±0.2 pg/mL) (P<.0001). ET-1 serum concentrations did not vary significantly among various EDN genotypes in patients (P=.378) and controls (P=.6164). Hence, we conclude that EDN K198N genotypes were not related to either ET-1 concentration or incidence of early-onset AMI in Egyptians. But, AMI patients had higher ET-1 concentrations than controls.

Association of Thrombospondin-1 (N700S) and Thrombospondin-4 (A387P) Gene Polymorphisms with the Incidence of Acute Myocardial Infarction in Egyptians

BACKGROUND: Thrombospondin (TSP) 1 and 4 are extracellular matrix glycoproteins that me- diate cell proliferation, platelet aggregation and inflammatory response. Conflicting data addressed the possible contribution of TSP-1 and TSP-4 gene polymorphisms to acute myocardial infarction (AMI). OBJECTIVE: Our study aimed to examine the association of TSP-1 (N700S) and TSP-4 (A387P) genetic variants with the incidence of AMI in Egyptians. It also correlated TSP-1 variants to TSP-1 and TNF-α serum concentrations while TSP-4 variants to IL-8 concentration identifying TSPs' contribution to vascular inflammation. METHODS: Genotyping was done in 214 subjects; 114 AMI patients and 100 controls using PCR-RFLP analysis. Serum Tsp-1, TNF-α and IL-8 levels were measured by ELISA assay. RESULTS: For TSP-4, (GC and CC) genotype distribution and the (C) allele frequency were significantly higher in AMI patients than controls (p = 0.0186), (p = 0.0117) respectively. In contrast, TSP-1 genotypes and allele frequencies showed no significant difference between AMI and controls (p = 0.7124 and p = 0.7201, respectively). Serum TSP-1, TNF-α and IL-8 concentrations were significantly elevated in AMI compared to controls (p = 0.0146, p < 0.0001 and p = 0.0057) respectively. Serum IL-8 levels had a significant difference among TSP-4 genotypes (p= 0.0368), being highest in the mutant C allele. Serum TSP-1 and TNF-α concentrations showed no significant difference among TSP-1 genotypes, but there was a positive correlation between both concentrations in AMI patients (p = 0.0014), (r = 0.4125). CONCLUSION: TSP-4 A387P polymorphism, but not TSP-1 polymorphism, is an independent risk factor for AMI in the Egyptians.

C242T polymorphism of NADPH oxidase p22phox gene reduces the risk of coronary artery disease in a random sample of Egyptian population.

The p22phox protein subunit is essential for NADPH oxidase activity. The prevalence of C242T variants of p22phox gene was studied in 101 healthy Egyptian controls and 104 acute myocardial infarction (AMI) Egyptian patients. Contribution of oxidative stress, represented by serum oxidized-LDL (ox-LDL), in development of AMI was also examined and correlated with C242T gene variants. Genotyping and ox-LDL were assessed by PCR-RFLP and ELISA. Results showed that wild type CC genotype is prevalent in 27 % of controls; CT and TT are in 72 and 1 %. In patients, the distribution was 40.2, 59.8 and 0 % for CC, CT and TT; respectively, showing a significant difference (p = 0.0259). Serum ox-LDL levels were higher in patients than controls (p ≤ 0.0001). Subjects having CT genotype had lower levels of ox-LDL than CC genotype (p ≤ 0.005). C242T polymorphism of p22phox gene of NADPH oxidase is a novel genetic marker associated with reduced susceptibility to AMI.

Endothelial nitric oxide synthase (G894T) gene polymorphism in a random sample of the Egyptian population: comparison with myocardial infarction patients.

AIM: The aim of this study was to detect endothelial nitric oxide synthase (eNOS) Glu298Asp gene variants in a random sample of the Egyptian population, compare it with those from other populations, and attempt to correlate these variants with serum levels of nitric oxide (NO). The association of eNOS genotypes or serum NO levels with the incidence of acute myocardial infarction (AMI) was also examined. METHODS: One hundred one unrelated healthy subjects and 104 unrelated AMI patients were recruited randomly from the 57357 Hospital and intensive care units of El Demerdash Hospital and National Heart Institute, Cairo, Egypt. eNOS genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. Serum NO was determined spectrophotometrically. RESULTS: The genotype distribution of eNOS Glu298Asp polymorphism determined for our sample was 58.42% GG (wild type), 33.66% GT, and 7.92% TT genotypes while allele frequencies were 75.25% and 24.75% for G and T alleles, respectively. No significant association between serum NO and specific eNOS genotype could be detected. No significant correlation between eNOS genotype distribution or allele frequencies and the incidence of AMI was observed. CONCLUSION: The present study demonstrated the predominance of the homozygous genotype GG over the heterozygous GT and homozygous TT in random samples of Egyptian population. It also showed the lack of association between eNOS genotypes and mean serum levels of NO, as well as the incidence of AMI.