The risk of bone fractures in dementia patients receiving acetylcholinesterase inhibitors: a meta-analysis.

Aim: The authors aimed to conduct a meta-analysis to determine if acetylcholinesterase inhibitors may pose a direct threat, increasing the incidence of fractures in dementia patients. Methods: PubMed, Scopus, and Cochrane Library were searched. Inclusion criteria were any original studies that demonstrated the link between acetylcholinesterase inhibitors and the incidence of fracture in patients with dementia. RevMan(5.4) was used. Results: Seven observational studies were included. The total number of patients included in the acetylcholinesterase inhibitors group is 274 332 and 290 347 in the control group. The pooled analysis showed that the risk of bone fracture was not statistically different between dementia patients who received acetylcholinesterase inhibitors and those who did not receive them (odds ratio=1.44, CI 0.95, 2.19, P=0.09). Subgroup analysis showed no statistically significant difference between dementia patients who took acetylcholinesterase inhibitors, and those who didn't take acetylcholinesterase inhibitors in those more than or equal to 80 years old and those less than 80 years old (P=0.44) and (P=0.34) respectively. However, our results showed a statistically significant association between dementia patients who received acetylcholinesterase inhibitors and decreased fracture risk in those receiving the treatment for more than or less than 2 years (risk ratio=0.48, CI= 0.45, 0.51, P<0.00001) and (risk ratio=0.84, CI 0.70, 0.99, P=0.04), respectively. Conclusion: Our study revealed no role for acetylcholinesterase inhibitors in increasing the risk of fracture compared with controls. Hence, based on our analysis, they might have a protective role against fracture when used for long periods considering their positive action on bone growth and development. Therefore, Acetylcholinesterase inhibitors could be considered a safe option for improving cognitive functions in elderly demented patients without carrying any additional risks.

MicroRNA-29a and microRNA-122 expressions and other inflammatory markers among obese children with diabetes.

OBJECTIVES: This study was conducted to study the expression of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, interleukin-6 (IL-6), and other inflammatory markers among obese children with/and without diabetes mellitus. METHODS: One hundred obese children with diabetes in addition to 100 age- and sex-matched obese children without diabetes, and 100 age- and sex-matched apparently healthy children were included in the study. Expressions of both microRNA-29a and microRNA-122, and serum levels of sestrin-2, IL-6, tumor necrosis factor-α (TNF-α), and high sensitive-CRP (hsCRP) were measured for all included study populations. RESULTS: Study results showed that the expressions of both microRNA-29a and microRNA-122, serum levels of IL-6, TNF-α, and hsCRP were significantly higher among obese children with diabetes in comparison to both obese children without diabetes and healthy children. In contrast, serum sestrin level was significantly low among obese children with diabetes in comparison to the other study populations. Expressions of both microRNA-29a and microRNA-122 were correlated with waist circumference, BMI, total cholesterol, triglycerides, LDL-cholesterol, HbA1c, c-peptide, glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP, and TNF-α among obese children with diabetes. However, serum sestrin-2 level was correlated inversely with these parameters. Higher expressions of both microRNA-29a and microRNA-122 among obese children either with or without diabetes mellitus (DM) can suggest their roles in the development of obesity among children. CONCLUSIONS: The study results can hypothesize that down-regulation of these micro-RNAs may solve this health problem with its sequelae, a hypothesis that needs more studies.

Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension.

Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks. The control rats were injected with the vehicle for the same period. The metformin-treated group received 200 mg/kg metformin daily for 10 weeks, beginning week 1, and received TAA injections with dosage and timing similar to those of the model group. All rats were culled at week 10. It was observed that TAA induced substantial renal injury, as demonstrated by significant kidney tissue damage and fibrosis, as well as augmented blood and kidney tissue levels of urea, creatinine, inflammation, oxidative stress, dyslipidemia, tissue inhibitor of metalloproteinases-1 (TIMP-1), and hypertension. TAA nephrotoxicity substantially inhibited the renal expression of phosphorylated AMPK. All these markers were significantly protected by metformin administration. In addition, a link between kidney fibrosis and these parameters was observed. Thus, metformin provides profound protection against TAA-induced kidney damage and fibrosis associated with the augmentation of the tissue protective enzyme AMPK and inhibition of oxidative stress, inflammation, the profibrogenic gene TIMP-1, dyslipidemia, and hypertension for a period of 10 weeks in rats.

Lower Extremity Arterial Disease in Type 2 Diabetes Mellitus: Metformin Inhibits Femoral Artery Ultrastructural Alterations as well as Vascular Tissue Levels of AGEs/ET-1 Axis-Mediated Inflammation and Modulation of Vascular iNOS and eNOS Expression.

Lower extremity arterial disease (LEAD) is a major risk factor for amputation in diabetic patients. The advanced glycation end products (AGEs)/endothelin-1 (ET-1)/nitric oxide synthase (NOS) axis-mediated femoral artery injury with and without metformin has not been previously investigated. Type 2 diabetes mellitus (T2DM) was established in rats, with another group of rats treated for two weeks with 200 mg/kg metformin, before being induced with T2DM. The latter cohort were continued on metformin until they were sacrificed at week 12. Femoral artery injury was established in the diabetic group as demonstrated by substantial alterations to the femoral artery ultrastructure, which importantly were ameliorated by metformin. In addition, diabetes caused a significant (p < 0.0001) upregulation of vascular tissue levels of AGEs, ET-1, and iNOS, as well as high blood levels of glycated haemoglobin, TNF-α, and dyslipidemia. All of these parameters were also significantly inhibited by metformin. Moreover, metformin treatment augmented arterial eNOS expression which had been inhibited by diabetes progression. Furthermore, a significant correlation was observed between femoral artery endothelial tissue damage and glycemia, AGEs, ET-1, TNF-α, and dyslipidemia. Thus, in a rat model of T2DM-induced LEAD, an association between femoral artery tissue damage and the AGEs/ET-1/inflammation/NOS/dyslipidemia axis was demonstrated, with metformin treatment demonstrating beneficial vascular protective effects.

Metformin Is Associated with the Inhibition of Renal Artery AT1R/ET-1/iNOS Axis in a Rat Model of Diabetic Nephropathy with Suppression of Inflammation and Oxidative Stress and Kidney Injury.

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.

Vitamin E suppresses aortic ultrastructural alterations induced by toxic doses of monosodium glutamate / La vitamina E suprime las alteraciones ultraestructurales aórticas inducidas por dosis tóxicas de glutamato monosódico

SUMMARY: An association between certain food additives and chronic diseases is reported. Current study determined whether administering toxic doses of the food additive monosodium glutamate (MSG) into rats can induce aortopathy in association with the oxidative stress and inflammatory biomarkers upregulation and whether the effects of MSG overdose can be inhibited by vitamin E. MSG at a dose of (4 mg/kg; orally) that exceeds the average human daily consumption by 1000x was administered daily for 7 days to the rats in the model group. Whereas, rats treated with vitamin E were divided into two groups and given daily doses of MSG plus 100 mg/ kg vitamin E or MSG plus 300 mg/kg vitamin E. On the eighth day, all rats were culled. Using light and electron microscopy examinations, a profound aortic injury in the model group was observed demonstrated by damaged endothelial layer, degenerated smooth muscle cells (SMC) with vacuoles and condensed nuclei, vacuolated cytoplasm, disrupted plasma membrane, interrupted internal elastic lamina, clumped chromatin, and damaged actin and myosin filaments. Vitamin E significantly protected aorta tissue and cells as well as inhibited MSG-induced tissue malondialdehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). The highest used vitamin E dosage was more effective. Additionally, a significant correlation was observed between the aortic injury degree and tissue MDA, TNF-α, IL-6, and superoxide dismutase (SOD) levels (p=0.001). Vitamin E effectively protects against aortopathy induced by toxic doses of MSG in rats and inhibits oxidative stress and inflammation.

RESUMEN: Se reporta una asociación entre ciertos aditivos alimentarios y enfermedades crónicas. El objetivo de este estudio fue determinar si la administración de dosis tóxicas del aditivo alimentario glutamato monosódico (MSG) en ratas puede inducir aortopatía en asociación con el estrés oxidativo y la regulación positiva de los biomarcadores inflamatorios y si el efecto de una sobredosis de MSG se puede inhibir con vitamina E. Se administró MSG diariamente durante 7 días una dosis de (4 g/kg; por vía oral) que excede el consumo diario humano promedio, en 1000x a las ratas del grupo modelo. Mientras que las ratas tratadas con vitamina E se dividieron en dos grupos y se administraron dosis diarias de MSG más 100 mg/kg de vitamina E o MSG más 300 mg/kg de vitamina E. Todas las ratas fueron sacrificadas en el octavo día. Usando exámenes de microscopía óptica y electrónica, se observó una lesión aórtica profunda en el grupo modelo demostrada por una capa endotelial dañada, células musculares lisas degeneradas (SMC) con vacuolas y núcleos condensados, citoplasma vacuolado, membrana plasmática rota, lámina elástica interna interrumpida, cromatina agrupada y filamentos de actina y miosina dañados. La vitamina E protegió significativamente el tejido y las células de la aorta, además de inhibir el malondialdehído tisular (MDA) inducido por MSG, la interleucina-6 (IL-6) y el factor de necrosis tumoral alfa (TNF-α). La dosis más alta de vitamina E utilizada fue más efectiva. Además, se observó una correlación significativa entre el grado de lesión aórtica y los niveles tisulares de MDA, TNF-α, IL-6 y superóxido dismutasa (SOD) (p=0,001). La vitamina E efectivamente protege contra la aortopatía inducida por dosis tóxicas de MSG en ratas e inhibe el estrés oxidativo y la inflamación.

Quercetin protects against acetaminophen-induced acute nephrotoxicity associated with the inhibition of biomarkers of acute kidney injury in rats / La quercetina protege contra la nefrotoxicidad aguda inducida por acetaminofén asociada con la inhibición de biomarcadores de lesión renal aguda en ratas

Acetaminophen (also called paracetamol, or APAP) causes acute kidney injury after accidental or intentional ingestion of a toxic dose of the drug. We tested whether the antioxidant and anti-inflammatory agent, quercetin (QUR) given alone can protect against acute nephrotoxicity induced by APAP overdose in a rat model of APAP-induced acute kidney injury. Rats were either given a single dose of APAP (2 g/kg) before being sacrificed after 24 hours or were pre-treated for 7 days with QUR (50 mg/kg) before being given a single dose of APAP and then sacrificed 24 hours post APAP ingestion. Kidneys were examined by light microscopy after staining with hematoxylin and eosin (H&E) and collected blood samples were assayed for biomarkers of oxidative stress, inflammation, and kidney injury. H&E stained sections of kidney from the model group of rats (APAP) showed substantial damage to the kidney architecture as demonstrated by widening of Bowman's space, tubular dilatation, vacuolization of tubular epithelium, and congested dilated blood vessels, which were partially protected by QUR. In addition, APAP significantly (p<0.05) increased blood levels of urea, creatinine, malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-a), and interleukin-6 (IL-6), which were significantly (p<0.05) reduced by QUR. These results indicate that quercetin partially protects against APAP-induced acute kidney injury in rats, which is associated with the inhibition of biomarkers of oxidative stress and inflammation and kidney injury.

El acetaminofeno (también llamado paracetamol o DCI) causa daño renal agudo después de la ingestión accidental o intencional de una dosis tóxica del medicamento. En el estudio analizamos si el agente antioxidante y antiinflamatorio, la quercetina (QUR) administrada sola, puede proteger contra la nefrotoxicidad aguda inducida por sobredosis de DCI en un modelo de rata. Las ratas recibieron una dosis única de DCI (2 g / kg) antes de ser sacrificadas después de 24 horas o fueron pretratadas durante 7 días con QUR (50 mg / kg) antes de recibir una dosis única de DCI y luego sacrificadas 24 horas post ingestión. Los riñones se examinaron mediante microscopía óptica después de la tinción con hematoxilina y eosina (H&E) y las muestras de sangre recolectadas se analizaron para detectar biomarcadores de estrés oxidativo, inflamación y daño renal. Las secciones de riñón teñidas con H&E del grupo modelo de ratas (DCI) mostraron un daño sustancial a la arquitectura del riñón, como lo demuestra la ampliación del espacio de Bowman, la dilatación tubular, la vacuolización del epitelio tubular y los vasos sanguíneos dilatados congestionados, que estaban parcialmente protegidos por QUR. Además, DCI aumentó significativamente (p <0,05) los niveles sanguíneos de la urea, creatinina, malondialdehído (MDA), factor de necrosis tumoral alfa (TNF-a) e interleucina-6 (IL-6), los que fueron reducidos significativamente (p < 0,05) por QUR. Estos resultados indican que la quercetina protege parcialmente contra la lesión renal aguda inducida por DCI en ratas, asociada con la inhibición de biomarcadores de estrés oxidativo, inflamación y lesión renal.

Association of ELMO1 gene polymorphism and diabetic nephropathy among Egyptian patients with type 2 diabetes mellitus.

BACKGROUND AND OBJECTIVE: Diabetic nephropathy (DN) is the most common cause of end stage renal failure or even death among patients with type 2 diabetes mellitus. Genetic predisposition is widely studied among these patients to identify manageable aspects of the disease pathogenesis. This study was carried out to test the association of engulfment and cell motility 1 (ELMO1) gene polymorphism with DN among Egyptians. ELMO1 is required for phagocytosis of apoptotic cells and cell motility. METHODS: This case-control study was conducted on type 2 diabetic patients who attended Suez Canal University Hospital, Egypt, between November 2016 and October 2017. Peripheral blood was collected from 200 diabetic patients (without nephropathy), 200 patients with DN, and 100 healthy controls for DNA extraction. The single nucleotide polymorphism of ELMO1 (rs741301) was genotyped using real-time polymerase chain reaction and the allele discrimination technique. RESULTS: GG genotype was significantly associated with DN (odds ratio [OR] = 2.7; 95% confidence interval [CI]: 1.4-5.3) (P = .016). The OR for the high-risk allele (G) was 1.9 with 95% CI from 1.5 to 2.9 (P < .001). CONCLUSION: ELMO1 gene (rs741301) polymorphism is a candidate variant in the predisposition to DN.

PPARα receptor expression in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is considered one of the major worldwide epidemics. It accounts for billions of cardiovascular disease events and deaths. Till now, major basics of MS are not fully clarified. Peroxisome Proliferator-Activated Receptor-α (PPARα) displays a ligand-activated transcription factor. It is involved in the regulation of many metabolic processes including inflammation, lipid, and glucose metabolism. Therefore, this study investigated the leucocytic expression of PPARα in a metabolic patient in comparison to healthy controls. METHODS: 100 subjects with MS were recruited, in addition to 100 subjects without any obvious metabolic disorders as healthy controls. Expression of PPARα and CD 36 were analyzed on different leucocytic populations using optimized flow-cytometric analysis. Correlations of the expression of both indexes with different clinical and laboratory parameters were analyzed. RESULTS: The eosinophilic expression of PPARα was found to be lower in subjects with MS in comparison to the healthy controls (p value 0.001). Also, PPARα expression, on most of the leucocytic populations, was inversely correlated with waist circumferences among the study populations. CONCLUSION: Circulated eosinophilic expression of PPARα protein is reduced in MS subjects. This conclusion may explain the endothelial dysfunction and obesity associated with MS, as well as it may help in the management of this worldwide health problem.

Neutrophil chemokines levels in different stages of nephrotic syndrome.

Nephrotic syndrome (NS) is a disease of glomerular filtration barrier failure presenting with variable degrees of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Inflammation may contribute to the pathogenesis of NS. The aim of this study was to monitor the serum levels of three cytokines [i.e., granulocyte chemotactic protein-2 (GCP-2), growth-related oncogene-α (GRO-α), and interleukin-8 (IL-8)] in different stages of NS and to find out whether changes in the levels of these cytokines could be related to the severity of NS. This study included 125 patients who were divided into 40 patients with nephrotic range proteinuria (NRP), 45 patients with NS, and 40 patients who were in remission. This study also included 80 healthy participants as a control group. Enzyme-linked immunosorbent assay was used for the determination of the plasma levels of GRO-α, GCP-2, and IL-8. GCP-2 plasma levels were significantly higher in the NS and NRP groups when compared to the control group, whereas the GRO-α and IL-8 levels were significantly higher in all patient groups in comparison with the control group. All these chemokine levels were significantly decreased in remission as compared with the participants in the NS group (P <0.0001). There was a significant correlation between the cytokine levels and proteinuria and serum albumin in the NS group (P <0.0001). However, in the follow-up group, GCP-2 levels were significantly lower during remission as compared to those with active NS (P <0.0001). Our findings suggest that the pro-inflammatory cytokines GCP-2, GRO-α, and IL-8 could play a role in the pathogenesis of NS, particularly glomerular permeability.

α-Adducin gene promoter DNA methylation and the risk of essential hypertension.

This study was conducted to test the association between promoter DNA methylation of α-Adducin (ADD1) gene and the risk of essential hypertension (EH). A total of 150 EH patients and 100 aged- and gender-matched controls were investigated. DNA methylation levels of five cytosine-phosphate-guanine (CpG) dinucleotides on ADD1 promoter were measured employing bisulfite pyrosequencing technology. Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among males. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r = -0.703). These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders.

T-helper 17 cytokines (interleukins 17, 21, 22, and 6, and tumor necrosis factor-α) in patients with alopecia areata: association with clinical type and severity.

BACKGROUND: Alopecia areata (AA) is an organ-specific autoimmune disease characterized by T-cell infiltrates and cytokine production. T-helper 17 (Th17) cells are crucially involved in the pathogenesis of autoimmune diseases. OBJECTIVES: Our aim was to assess the association of Th17 with AA. We examined interleukin (IL)-17, IL-21, IL-22, IL-6, and tumor necrosis factor-alpha (TNF-α) levels in the serum of patients with AA and studied their association with clinical type and severity of AA. SUBJECTS AND METHODS: The serum concentrations of IL-17, IL-21, IL-22, IL-6, and TNF-α were measured in 47 patients with AA and 40 healthy controls. The clinical type of AA was determined, and the severity of hair loss was assessed in accordance with the Alopecia Areata Investigational Assessment Guideline criteria. RESULTS: The serum concentrations of IL-17, IL-21, IL-22, IL-6, and TNF-α were significantly higher in patients with AA as compared with healthy controls (mean: IL-17 33.23 ± 11.58 vs. 4.62 ± 1.88 pg/ml; P = 0.000, IL-21 62.10 ± 6.11 vs. 48.38 ± 3.31 pg/ml; P = 0.000, IL-22 19.27 ± 3.36 vs. 7.09 ± 1.62 pg/ml; P = 0.000, IL-6 17.18 ± 3.08 vs. 4.59 ± 1.66 pg/ml; P = 0.000, TNF-α 19.94 ± 3.59 vs. 9.95 ± 2.42 pg/ml; P = 0.000, respectively). There were significant positive correlations between serum IL-17, TNF-α, and disease severity. There was also significant positive correlation between serum IL-22 and duration of AA. CONCLUSION: Our results showed high serum levels of Th17 cytokines among patients with AA that may suggest a functional role of these cytokines in the pathogenesis of this important skin disease. It could also provide the rationale for new treatment strategies in AA.

Study of the association of adrenomedullin and basic-fibroblast growth factors with the peripheral arterial blood flow and endothelial dysfunction biomarkers in type 2 diabetic patients with peripheral vascular insufficiency.

BACKGROUND: Progressive micro-vascular vaso-degeneration is the major factor in progression of diabetic complications. Adrenomedullin (AM) and basic-Fibroblast growth factor (b-FGF) are strongly correlated with angiogenesis in vascular diseases. This study aims to provide base line data regarding the vascular effects and correlation of AM, and b-FGF with the peripheral blood flow in diabetic patients with peripheral vascular disease (PVD), and their effect on endothelial dysfunction markers. Ninety age- and sex matched females were enrolled in the study: 30 were controls, 30 had diabetes without complications (group II) and 30 had diabetes with PVD (group III) diagnosed by ankle/ brachial index (A/BI). Plasma levels of AM, b-FGF, intercellular adhesion molecule -1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were measured by indirect enzyme immunoassay (ELISA). RESULTS: There was a significant increase in plasma AM, VCAM-1and ICAM-1, while a significant decrease in plasma b-FGF in diabetic patients with PVD (p < 0.05). A positive correlation was observed between plasma AM, b-FGF and A/BI and a negative correlation with VCAM -1 and ICAM in diabetic PVD. AM was not a predictor, while b-FG, VCAM-1 and ICAM-1 could be predictors for peripheral blood flow in diabetic PVD. CONCLUSION: This study elucidates for the first time that AM and b-FGF are correlated and have a direct impact on the peripheral blood flow, the rise of AM in diabetic PVD may be a consecutive and compensatory vasculo-protective effect as its angiogenic and anti-inflammatory properties act to relief the endothelial insult. Down expression of b-FGF may be a predisposing factor for micro-vascular derangement. It is not clear if the rise of AM and the decline of b- FGF levels may be consequences or predisposing factors for VCAM-1 and ICAM-1 elevation as these endothelial dysfunction biomarkers could reduce peripheral blood flow and vascular integrity. It is optimistic to believe that drug intervention through AM and b-FGF administration together with reversing the endothelial inflammatory process by targeting VCAM and ICAM could reduce the prevalence of diabetic vascular complications, reduce the risk of cerebrovascular and cardiovascular morbidity in diabetes through normalizing vascular endothelium function and peripheral blood flow.

Evaluation of resistance to anti-platelet therapy in patients with coronary heart disease in a developing country.

BACKGROUND: Resistance to anti-platelet therapy whether defined by the laboratory detection of platelet function or the recurrence of cardiovascular events, has received extensive coverage in the literature coming predominantly from developed countries and very scanty information comes from developing countries. We aim to document the prevalence of aspirin and clopidogrel resistance in Saudi patients with coronary heart disease (CHD) and to probe the possible responsible mechanism[s]. METHODS: 238 patients with CHD were enrolled from the outpatient clinic and wards of King Khalid University Hospital, Riyadh. Platelet function testing was undertaken using both optical aggregometry in platelet rich plasma as well as the Platelet Function Analyzer [PFA100] which uses whole blood. RESULTS: Agonist-induced platelet aggregation in response to arachidonic acid-induction: The prevalence of residual activity was detected in 12.6% patients. Resistance to clopidogrel as reflected by the residual aggregation responses to ADP was detected in 25.7%. PFA100 closure time: Closure times for collagen and epinephrine cartridges that are shorter than the maximum for local reference of 84 - 198 seconds were detected in around 30% of patients on therapy. There was no significant relationship between diabetes mellitus, smoking, dyslipidemia, or consumption of non-steroidal anti-inflammatory drugs and the resistance to anti-platelet therapy. CONCLUSIONS: Resistance to anti-platelet therapy is quite prevalent among patients with CHD in Saudi Arabia and compares favorably with reports in the literature. However, the lack of a significant relationship between resistance to antiplatelet therapy and the above-mentioned conditions could be due to small numbers.

The role of interleukin-6 promoter polymorphism -174G/C in Saudi women with hypertensive disorders of pregnancy.

OBJECTIVE: To study the relationship between -174 GC interleukin-6 single nucleotide polymorphism and hypertensive disorders of pregnancy (HDP) in Saudi women. METHODS: In this case-control study, 109 HDP patients and 100 women with normal pregnancy as a control group were studied. The HDP study group constituted of 60 women with gestational hypertension (GH) and 49 women with preeclampsia (PE). All women were randomly selected from the antenatal clinic and the prenatal and postnatal wards at the Antenatal Clinic and the Obstetric Ward of King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from April 2010 to December 2011. The -174 GC of IL-6 SNP was determined using real time polymerase chain reaction, allele discrimination technique. RESULTS: Distribution of -174 GC of IL-6 genotype in HDP patients was GG (58.5%), GC (31.1%), and CC (10.4%), while in the control group was GG (67%), GC (30.9%), and CC (2.1%). The CC homozygosity was significantly associated with HDP (odds ratio [OR] = 5.76; 95% confidence interval [CI] 1.23-27.06, p=0.03). This association only manifested with GH (OR = 7.65; 95% CI = 1.54-38.03, p=0.01). However, no significant association was found with PE (OR = 3.48; 95% CI = 0.55-21.99, p=0.19). CONCLUSION: The results indicate a positive association between -174 GC of IL-6 genotype and the risk of HDP. Genotypes CC and GC are associated with increased risk of GH but not with PE, suggesting that they are of differing genetic predisposition/pathophysiology.

Association of cluster of differentiation 36 gene variant rs1761667 (G>A) with metabolic syndrome in Egyptian adults.

OBJECTIVE: To investigate the relationship between cluster of differentiation (CD)36 gene variant rs1761667 (G>A) and metabolic syndrome (MetS) and its components in Egyptian patients. METHODS: This case-control study was conducted on MetS patients attending Suez Canal University Hospital, Egypt from November 2010 to October 2011. Peripheral blood was collected from 100 patients and 100 healthy controls for DNA extraction. The single nucleotide polymorphism (SNP) CD36 gene rs1761667 (G>A) was genotyped using real-time polymerase chain reaction, and allele discrimination technique. RESULTS: Distribution of CD36 genotypes in the patient group was AA (n=25), AG (n=70), and GG (n=5) while in the control group it was AA (n=51), AG (n=48), and GG (n=1). Both AG and GG genotypes were significantly more prevalent among MetS patients (p<0.001). The odds ratio (OR) for the high risk allele (G) is 2 with 95% confidence interval from 1.30-3.07 (p<0.001). Patients with genotypes AG and GG had significantly higher systolic blood pressure, wider waist circumstance, and higher degree of dyslipidemia (p<0.001) than patients with genotype AA. CONCLUSION: Our findings show that CD36 rs1761667 SNP is positively associated with increased risk of MetS and its components with genotype AG heterozygotes showing highest frequency among MetS patients.