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Metabolic syndrome (MetS) is a cluster of metabolic abnormalities affecting ~25% of adults and is linked to chronic diseases such as cardiovascular disease, cancer, and neurodegenerative diseases. Oxidative stress and inflammation are key drivers of MetS. Hesperidin, a citrus bioflavonoid, has demonstrated antioxidant and anti-inflammatory properties; however, its effects on MetS are not fully established. We aimed to determine the optimal dose of hesperidin required to improve oxidative stress, systemic inflammation, and glycemic control in a novel mouse model of MetS. Male 5-week-old C57BL/6 mice were fed a high-fat, high-salt, high-sugar diet (HFSS; 42% kcal fat content in food and drinking water with 0.9% saline and 10% high fructose corn syrup) for 16 weeks. After 6 weeks of HFSS, mice were randomly allocated to either the placebo group or low- (70 mg/kg/day), mid- (140 mg/kg/day), or high-dose (280 mg/kg/day) hesperidin supplementation for 12 weeks. The HFSS diet induced significant metabolic disturbances. HFSS + placebo mice gained almost twice the weight of control mice ( p < 0.0001). Fasting blood glucose (FBG) increased by 40% ( p < 0.0001), plasma insulin by 100% ( p < 0.05), and HOMA-IR by 150% ( p < 0.0004), indicating insulin resistance. Hesperidin supplementation reduced plasma insulin by 40% at 140 mg/kg/day ( p < 0.0001) and 50% at 280 mg/kg/day ( p < 0.005). HOMA-IR decreased by 45% at both doses ( p < 0.0001). Plasma hesperidin levels significantly increased in all hesperidin groups ( p < 0.0001). Oxidative stress, measured by 8-OHdG, was increased by 40% in HFSS diet mice ( p < 0.001) and reduced by 20% with all hesperidin doses ( p < 0.005). In conclusion, hesperidin supplementation reduced insulin resistance and oxidative stress in HFSS-fed mice, demonstrating its dose-dependent therapeutic potential in MetS.

Background: Citrus bioflavonoids are polyphenolic compounds that are derived from citrus fruits and vegetables. Although they are well known for their powerful antioxidant properties, their effects on glycemic control are not well understood. This review aims to highlight the potential benefits of using citrus bioflavonoids in patients with type 2 diabetes mellitus and its metabolic complications, as well as the medicinal effects of known subclasses of naturally occurring citrus bioflavonoids., Methods: In this systematic review, a survey of studies was conducted from January 2012 to February 2023 using various databases (PubMed, Medline, Google Scholar, and Scopus) to determine the effects of citrus bioflavonoid supplementation on reducing oxidative stress, improving lipid profiles, and glycemic index in patients with diabetes mellitus, as well as the proposed mechanisms of action., Results: The results of the survey indicate that citrus bioflavonoids may have a positive impact on reducing oxidative stress levels in patients with type 2 diabetes mellitus. In addition to reducing oxidative stress, citrus bioflavonoids may also have a positive impact on other markers of diabetes. For example, studies have shown that they can reduce non-enzymatic protein glycation, which is a process that occurs when glucose molecules bind to proteins in the body., Conclusion: The reduction in oxidative stress that can be achieved using citrus bioflavonoids may help to maintain antioxidant levels in the body, thereby reducing the severity of diabetes and its complications. These findings suggest that citrus bioflavonoids may be a useful complementary therapy for patients with diabetes., Competing Interests: Declaration of competing interest All authors declare no conflict of interest exist., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Primary open-angle glaucoma (POAG) is a clinical progressive neuropathy which can lead to irreversible blindness if left untreated. A low level of serum Vitamin D3 is a major risk factor for glaucoma, and hence, represents a second target for glaucoma therapy following intraocular pressure (IOP). However, there is still controversy about whether there is a direct correlation between Vitamin D3 deficiency and the risk of increased IOP. This study aims to investigate the correlation between low serum levels of 1,24-dihydroxycholecalciferol and the development of open-angle glaucoma., Methods: The study included a total of forty-one patients with POAG. Patients were classified into whether they have chronic illnesses such as type 2 diabetes and hypertension. Matching control subjects of 20 healthy controls were also included in the study. Anthropometric measures and venous blood samples were taken from all participants for serum analysis of various biochemical markers including serum 1,25-dihydroxycholecalciferol (1,25(OH)2D) levels., Results: Overall, serum Vitamin D3 levels were 15% significantly lower in the patient's cohort with open-angle glaucoma as compared to the healthy participants ( P < 0.05). Among those, 63% of type 2 diabetic participants had significantly low levels of Vitamin D3 ( P < 0.01). There was also a significant 70% reduction in serum Vitamin D3 levels among the hypertensive participants, ( P < 0.001)., Conclusion: We concluded that lower serum 1,25(OH) 2D levels were significantly associated with an increased risk of open-angle glaucoma in patients with chronic illnesses., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Ophthalmology.)

Citrus bioflavonoids are polyphenolic plant-derived pigments found in high levels in oranges, lemons, grapefruits and other citrus fruits. The three most abundant types of citrus bioflavonoids are hesperidin, naringenin and eriocitrin. Citrus bioflavonoids have long been known to possess powerful free radical-scavenging properties and cardioprotective effects. The study involved the analysis of 10 commercially available citrus bioflavonoid supplements from three different countries: Australia, the United States and Canada. The supplements were tested for their citrus bioflavonoid content which varied from 0.8 to 33.3% w / w . The daily bioflavonoid dose varied from 19 mg to 560 mg. Hesperidin was the major citrus bioflavonoid in nine out of ten supplements. One supplement was found to contain less than 10% of the quantity of rutin claimed to have been added. The DPP-4 inhibitory potential, compared through an estimation of rutin equivalence, ranged from 1.9 mg to 400 mg per day. This data highlights the variability between the supplements in their potential to inhibit DPP-4 for subsequent health benefits.

The benefits of a Mediterranean Diet (MedDiet) in the management of diabetes have been reported, but the contribution of polyphenol-rich citrus fruit has not been studied widely. Here, we report the sub-study findings of a previously conducted MedDiet intervention clinical trial in patients with type 2 diabetes mellitus (T2DM), where we aimed to measure the diet intervention effects on plasma citrus bioflavonoids levels and biomarkers of inflammation and oxidative stress. We analysed plasma samples from 19 (of original 27) participants with T2DM who were randomly assigned to consume the MedDiet intervention or their usual diet for 12 weeks and then crossed over to the alternate diet. Compared with baseline, MedDiet significantly increased levels of the citrus bioflavonoids naringin, hesperitin and hesperidin (by 60%, 58% and 39%, respectively, p < 0.05) and reduced plasma levels of the pro-inflammatory cytokine IL-6 (by 49%, p = 0.016). Oxidative stress marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) decreased by 32.4% ( p = 0.128). Usual diet did not induce these beneficial changes. The reduced inflammatory profile of T2DM participants may, in part, be attributed to the anti-inflammatory actions of citrus bioflavonoids. Together with indications of improved oxidative stress, these findings add to the scientific evidence base for beneficial consumption of citrus fruit in the MedDiet pattern.

Genetic variation in the angiotensin II type 1 receptor (AT1R) has an important effect on the outcome of acute coronary syndrome (ACS) initiated treatment with captopril. This study aims to investigate the impact of genetic polymorphism of AT1R (rs5186 and rs275651) on the ACS outcome in Iraqi patients treated with captopril. A total of 250 Iraqi individuals with ACS were included in this case-control study and they were divided into two study groups; Study group 1 included 125 participants who were prescribed captopril, 25 mg twice daily and study group 2 included 125 participants who received no captopril as part of their ACS treatment (control study). The AT1R gene (rs5186) CC genotype was found to be associated with ST-elevation myocardial infarction (STEMI) (Odd's ratio (O.R) = 1.2, P  = 0.7), while AC was associated with Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina (UA) (O.R = 1.2, P  = 0.8). AC genotype is more prone to have Percutaneous coronary intervention (PCI) after ACS attack (O.R = 1.2, P  = 0.6). CC genotype had a risk to get less improvement (O.R = 1.6, P  = 0.5), so might require higher doses of captopril during acute coronary insult. The AT1R gene (rs275651) AA genotype was associated with UA (O.R = 1.3, P  = 0.9). AA and AT genotypes were more prone to have PCI after ACS attack (O.R = 3.9 P  = 0.2, O.R = 3.5, P  = 0.3 respectively) and thus requiring higher doses of captopril. We conclude that the AT1R rs5186, rs275651 genetic polymorphisms might partially affect the clinical outcome of ACS patients treated with captopril and might have captopril resistance which requires higher doses., Competing Interests: Conflict of interestAll authors declare that they have no conflict of interest., (© Association of Clinical Biochemists of India 2019.)

Acute kidney injury (AKI) is characterized by fast decline in renal function within a short period of time. Renal ischemic-reperfusion (I-R) injury is the main cause of AKI. This study aims to investigate the possible nephroprotective effect of lycopene on renal ischemic-reperfusion injury in mice model. Forty Swiss Albino adult male mice were randomly allocated onto one of the four study groups: sham group: mice had median laparotomy under anesthesia with no procedures performed, renal tissues and blood samples were collected. ischemic-reperfusion group (I-R-control): mice underwent median laparotomy under anesthesia, followed by 30 min bilateral renal ischemia. Renal tissues and blood samples were collected after 2 h from reperfusion. Vehicle-treated group: mice were pretreated with intra 1% dimethyl sulfoxide 30 min before inducing ischemia. Lycopene-treated group: mice were pretreated with 10 mg/kg intraperitoneal injection of lycopene 30 min before inducing renal ischemia. Renal tissues, and blood samples were collected after 2 h from reperfusion. Blood and tissue samples were collected to look for evidence of inflammation and necrosis. Blood urea nitrogen, serum creatinine as well as plasma NGAL levels were significantly increased in the active control group ( P  ≤ 0.05), when compared to the sham group. Similarly, renal levels of Notch2/Hes 1, TLR 2, IL-6, Bax, and F2-isoprostane were significantly increased in the active control group as compared to the sham group ( P  ≤ 0.05). Moreover, lycopene treatment was found to be significantly effective in reducing the increased levels of these markers after I-R injury ( P  ≤ 0.05)., Competing Interests: Conflict of interestThe authors declare that they have no potential conflict of interest., (© Association of Clinical Biochemists of India 2019.)

Background and Aims: Several commercially available phytosterol supplements are promoted for their cholesterol-lowering effects. However, limited information is available about their potential anti-hyperglycaemic effects. This study aimed to evaluate the dipeptidyl peptidase-4 (DPP-4) inhibitory effects of phytosterol supplements in silico and in vitro to determine their potential for anti-diabetic activity., Methods: Docking studies were carried out in silico to evaluate the potential for interactions between three major phytosterol compounds (stigmasterol, β-sitosterol, campesterol) and the DPP-4 enzyme, the enzyme that is inhibited by the anti-diabetic gliptins. Gas chromatography-tandem mass spectrometry (GC-MS/MS) was used to analyse three different supplements for phytosterol content. DPP-4 inhibitory activity was tested in vitro for these phytosterol supplements and two major phytosterol standards., Results: In silico calculations predicted free binding energies for DPP-4 with the phytosterols to be: stigmasterol -8.78 kcal/mol; β-sitosterol -8.70 kcal/mol; campesterol -8.40 kcal/mol. These binding energies indicated a potential for significant DPP-4 inhibition. However, these results were not supported by the in vitro studies. Stigmasterol and β-sitosterol had an IC 50  > 50 mg/ml (maximum tested concentration) and the Thompson's Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC 50  > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC 50 value of 40 mg/ml which was attributed to β-carotene content., Conclusions: Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

This study aims to investigate the impact of ACE (rs4343) and AT1R (rs 5182) genetic polymorphisms on the outcome of acute coronary syndrome (ACS) in patients on captopril. Two hundred and fifty participants with ACS were included in this study (Group 1 (120) participants on captopril 25 mg twice daily and Group 2 (130) participants received no captopril (control study)). Participants were genotyped for ACE (rs4343) and AT1R (rs5182) polymorphisms and the phenotype was determined. ACE polymorphism (rs 4343) GG and GA genotypes are more related to STEMI (OR = 1.7, 1.5 respectively) and NSTEMI (OR = 3, 3.8 respectively), and they were more prone to have Percutaneous Coronary Intervention after ACS attack (OR = 11.6, 14.1 respectively). AT1R (rs 5182) CT genotype is mildly associated with STEMI (OR = 1.1), but also prone to have PCI after ACS attack (OR = 1.6) while TT genotype has a risk to get less improvement (OR = 1.8)., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: Various pressures exist for curricular change, including economic forces, burgeoning knowledge, broadening learning outcomes, and improving quality and outcomes of learning experiences. In an Australian 5-year undergraduate medical course, staff were asked to reduce teaching hours by 20% to alleviate perceived overcrowded preclinical curriculum, achieve operating efficiencies and liberate time for students' self-directed learning. Methods: A case study design with mixed methods was used to evaluate outcomes. Results: Teaching hours were reduced by 198 hours (14%) overall, lectures by 153 hours (19%) and other learning activities by 45 hours (7%). Summative assessment scores did not change significantly after the reductions: 0.4% increase, 1.5% decrease and 1.7% increase in Years 1, 2 and 3, respectively. The percentage of students successfully completing their academic year did not change significantly: 94.4% before and 93.3% after the reductions. Student evaluations from eVALUate surveys changed little, except workload was perceived to be more reasonable. Conclusions: Teaching hours, particularly lectures, can be moderately reduced with little impact on student learning outcomes or satisfaction with an undergraduate medical course.

Background & Objectives: This study investigates the association of two potential Fat mass and obesity associated gene (FTO) gene polymorphisms (rs9939609 and rs918031) as potential predictors of type 2 diabetes (T2D) in obese Iraqi population and their metabolic effects on hyperglycemia and insulin sensitivity., Materials & Methods: The study included 400 participants with obesity & T2D, with a matching 400 obese non-diabetic cohort. Venous blood samples were collected for DNA extraction. Using specific primers and restriction enzymes, genotyping was performed to identify the various alleles for each gene. The genotype and allele frequencies determined by multinomial logistic regression analysis for FTO single nucleotide polymorphisms (rs9939609) among all the study groups., Results: There is a two-fold increase in the risk of T2D within the homozygous genotype (TT) group (OR = 2.43, CI 95% 3.57-11.2, P ≤ 0.001) as compared to the wild type (TA). In addition, there was a significantly higher level of the minor allele genotype (T) in T2D patients when compared to the control group, (P ≤ 0.001)., Conclusion: We conclude that the FTO rs9939609 genotype significantly affect the development of insulin resistance, therefore the future occurrence of T2D, in obese individuals., (Copyright © 2019 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

This study aims to investigate the different clinically relevant allele variants (allele frequencies) of CYP2D6 gene and to determine whether a specific genotype of CYP2D6 gene (based on genetic polymorphism "allelic types" and combination) have impact on metoprolol effectiveness (clinical outcome) in patients who have acute coronary syndrome (ACS). The study included 250 patients with ACS who were classified into 2 study groups, 125 patients received metoprolol and served as a study group (Group1) and 125 who received no metoprolol therapy (due to contraindication to the medication) and served as a control group (Group 2). Venous blood samples were taken from all participants for DNA extraction. Urine samples were also collected to assess the metabolic ratio using High-performance liquid chromatography (HPLC) technique. There was significant variation in the distribution of Iraqi patients with respect to CYP2D6 allelic polymorphism as compared to similar patients in other countries. Besides, this significant difference existed in patients' outcome in terms of morbidity and mortality in respect to variable genotypes and phenotypes. We recommend a dose individualization of metoprolol in patients with ACS is essential to improve patients' outcome., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aims: Diabetic nephropathy (DN) is a serious microvascular complication of a longstanding hyperglycemia. This study aims to evaluate whether urinary neutrophil gelatinase-associated lipocalin (NGAL) and urinary Interleukin-18 possess a better diagnostic value than albumin creatinine ratio in assessing the severity of nephropathy in patients with type 2 diabetes mellitus (T2DM)., Material & Methods: Ninety participants diagnosed with T2DM were recruited and they were divided into three study groups according to their albumin/creatinine ratio (ACR): (Normoalbuminuria group, Microalbuminuria group, and Macroalbuminuria group). A matching of Ninety healthy subjects were included as controls. Blood and urine samples were collected to measure various markers of glycemic control and kidney function., Results: IL-18 levels were not changed significantly between all study groups (P > 0.05), despite a significant positive correlation between IL-18 and urinary albumin levels. NGAL levels were significantly increased in Microalbuminuria group and Macroalbuminuria group as compared to the control and Normoalbuminuria groups. NGAL was also positively correlated with urinary albumin and ACR, but negatively correlated with the age and body mass index. Receiver Operating Characteristic curves revealed that for early detection of DN, the best cutoff values to discriminate DN and diabetic without nephropathy groups were ˃ 21.4 ng/ml for NGAL (94.67 sensitivity, 26.67% specificity), ≤0.34 pg/mL for IL-18 (72% sensitivity, 53.33% specificity), and ˃29.8 mg/g for ACR (80% sensitivity, 100% specificity)., Conclusion: We conclude that the urinary ACR is a more accurate individual biomarker of DN when compared to both NGAL and IL-18., (Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO). Rats were exposed to a 30 min of ischemia then 3 h of reperfusion. At the end of reperfusion phase, rats were sacrificed then plasma, serum and tissue samples were obtained to measure markers of kidney oxidative stress and inflammation. Plasma levels of neutrophil gelatinase-associated lipocalin (NGAL), and tissue levels of interleukin-18 (IL-18) and malondialdehyde (MDA) were significantly lower in TAK-242 pretreated groups than the vehicle group and the control group (p < 0.05). Furthermore; serum levels of urea and creatinine were significantly lower in the TAK-242 pretreated groups as compared to the control group (p < 0.05). We conclude that administration of TAK-242 can be useful preventive method in attenuating the degree of acute kidney injury during ischemic reperfusion process as shown by a significant reduction of urinary inflammatory markers as well as significant reduction of urea and creatinine levels., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study compared dipeptidyl peptidase-4 (DPP-4) inhibitory activity of citrus bioflavonoid nutraceuticals compared with three gliptins. Citrus bioflavonoid standards and three commercially available citrus bioflavonoid supplements (Thompson's Super Bioflavonoid Complex ® (SB), Ethical Nutrients Bioflavonoids Plus Vitamin C ® (EN), and Country Life Citrus Bioflavonoids and Rutin ® (CB)) were considered in this study. Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis was undertaken to identify and quantitate the citrus bioflavonoids present in each supplement. The DPP-4 inhibitory activity was determined by fluorometric assay. All of the tested individual citrus flavonoids demonstrated DPP-4 inhibitory activity, with IC 50 values ranging from 485 μM (rutin) to 5700 μM (hesperitin and eriodictyol). Similarly, the flavonoid supplements had IC 50 values of 16.9 mg/mL (EN), 3.44 mg/mL (SB) and 2.72 mg/mL (CB). These values compare with gliptin IC 50 values of 0.684 μM (sitagliptin), 0.707 μM (saxagliptin) and 2.286 μM (vildagliptin). The supplement flavonoid content varied from 11.98% (CB) to 5.26% (EN) and 14.51% (SB) of tablet mass, corresponding to daily flavonoid doses of around 300, 150 and 400 mg, respectively, with CB and SB containing rutin at levels of 7.0% and 7.5% of tablet mass, respectively. While our data demonstrated that citrus bioflavonoid based supplements do possess DPP-4 inhibitory activity, they are several orders of magnitude less potent than gliptins. Further studies using higher concentrations of citrus bioflavonoids, as well as investigations into antioxidant properties which may add additional benefit are warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: Recovery of cardiac autonomic modulation following exercise can be measured using heart rate variability. The objective of this study was to investigate and compare recovery of autonomic cardiac regulation over three days following a single session of high intensity interval training compared to endurance training., Design: Nine untrained students completed two exercise protocols in a one-way crossover design. The endurance protocol consisted of 45min of moderate intensity cycling, and the high intensity interval protocol of six 30s sets of high intensity cycling., Methods: Cardiac autonomic activity recovery was measured over three days post-exercise for two hours immediately following each exercise session and each morning thereafter using linear and nonlinear heart rate variability analysis., Results: Both linear and nonlinear measures were significantly decreased immediately following exercise indicating loss of vagal activity. Root mean sum of squared differences (p=0.031) and high frequency (p=0.031) were suppressed following the interval exercise only. The long term correlation of the heart rate applying detrended fluctuation analysis was decreased immediately following endurance training (p=0.039) and trended to increase immediately following the interval protocol (p=0.156). Sample entropy was decreased immediately following both the endurance (p=0.023) and interval (p=0.031) protocols. No exercise effects were noted from 24h post exercise onwards., Conclusions: High intensity interval training had a greater impact on neurocardiac activity than moderate intensity endurance training as indicated by both linear and nonlinear heart rate variability measures., (Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.)

Background: Hypertension-induced cardiac dysfunction is variable among different anti-hypertensive medications. This study compares the effects of telmisartan and enalapril on echocardiographic parameters in hypertensive patients., Materials and Methods: This was a randomised single blinded study. Eighty hypertensive patients were included in this study and they were randomly allocated into two study groups: Group 1 included 40 patients who took telmisartan 80mg once daily for six months. Group 2 included 40 patients who took enalapril, 20mg once daily for six months. An additional 40 healthy participants were enrolled in the study as controls (Group 3). Baseline echocardiographic scan was done at the start of the study and after 6 months of treatment including assessment of left ventricular systolic and diastolic functions with assessment of left ventricular mass index, in addition to measurements of blood pressure, heart rate and double product., Results: Both group 1 and group 2 (telmisartan and enalapril groups respectively) showed comparable statistically significant improvement in the diastolic functional parameters (P<0.010), while both medications didn't demonstrate changes in the systolic functional parameters. Furthermore, telmisartan was significantly effective in reducing the interventricular septal thickness and left ventricular mass index (P<0.010)., Conclusions: Both drugs interfere with renin-angiotensin aldosterone system, protecting the myocardium from high blood pressure. Findings from our study provide key results for physicians in deciding the appropriate antihypertensive drug for each patient depending based on the patient's intolerability for either medication., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The role of homocysteine (Hcy) and associated oxidative stress processes in the metabolic syndrome (MetS) continuum has not been explored extensively. Changes in Hcy and associated oxidative stress in relation to the number of metabolic syndrome factors present are explored in this study., Method: Participants (n=266) attending a rural diabetes screening clinic had their medical history recorded as well as body mass index, Hcy, glucose, cholesterol, glutathione (GSH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) measured., Result: A significant elevation in Hcy (9.5μmol/L ±2 vs. 10.6μmol/L ±3, p=0.03) and 8-OHdG (307pg/mL ±516 vs. 1130pg/mL ±1155, p=0.0001) was observed between the noMetS and MetS groups. Hcy increased with the addition of MetS factors paralleled by 8-OHdG and GSH. A dramatic increase was seen in 8-OHdG, nearly doubling between 2 MetS and 3 MetS factors present (p=0.0001)., Conclusion: Homocysteine may be a useful marker together with 8-OHdG in assessing the extent of metabolic syndrome in a rural population., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

Background: Myocardial ischemia/reperfusion injury represents a clinically critical problem associated with coronary artery bypass graft surgery (CABG). The degree of oxidative stress, inflammation and apoptosis are increased during the reperfusion of the heart muscles following ischemia. The present study aims to examine the protective role of melatonin in ameliorating the degree of cardiac injury in patients undergoing bypass surgery, and whether this effect is a dose related., Methods: A total of forty-five patients who were undergoing elective CABG in (Al-Najaf Cardiac Center, Al-Najaf, Iraq) were included in this study for the period between January, 2015 and November, 2015. Participants were randomly allocated into 3 study groups: Placebo-controlled group (C), low dose melatonin treatment group, 10mg capsule once daily (M1) and high dose melatonin treatment group 20mg capsule once daily (M2)., Results: Compared to the control group, there was a significant increase in the ejection fraction (EF%) associated with a significant decline in heart rate (HR) among the M1 and M2 groups compared to the C group (P<0.05). In addition, there was a significant reduction in plasma levels of cardiac Troponin-I (CTnI), interleukin-1beta (IL-1β), Inducible nitric oxide synthase (iNOS) and caspase-3 enzymes in the melatonin groups (group M1 and M2) compared to the control group, (P<0.05) in Melatonin-treated groups. Comparing the two melatonin study groups, the changes in the parameters mentioned above were more significant in the M2 group compared to the M1 group (P<0.05)., Conclusion: These findings suggested that melatonin supplementation can ameliorate the degree of myocardial ischemic-reperfusion injury, dose dependent effects., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: This study aims to investigate the inflammatory response in Novolimus bioresorbable coronary scaffold implantation after a course treatment with trimetazidine (35mg tablet/twice daily for 4days)., Methods: This was a randomized single blind study. Forty diabetic patients with critical coronary stenosis were subjected to elective coronary scaffold implantation in Al-Najaf Center for Cardiac Surgery and Trans-Catheter Therapy, Najaf, Iraq, between January and July 2015. All patients were informed about the nature of the study and they signed the consent form before they included in the study. Patients were randomly allocated into the two study groups: Group 1 included 20 patients who did the elective coronary scaffold implementation without trimetazidine medication. Group 2 included 20 patients who did the elective coronary scaffold implementation with a course of the trimetazidine (35mg tablet/twice daily for 4days)., Results: There were significant reduction in the levels of the interleukin-6 and cardiac troponin-I in the trimetazidine-treated group (group 2) compared to the control group (group 1) (P<0.001), after 12h and 24h post-operative. This was associated with a significant rise in the levels of interleukin 10 in group 2 compared to group 1 (P<0.001). Pentraxin-3 was significantly reduced in group 2 but only 24h post-operative (P<0.006)., Conclusion: Our study concluded that trimetazidine minimizes the acute inflammatory response occurred due to systemic release of inflammatory markers into blood in diabetic patients undergoing elective Novolimus bioresorbable coronary scaffold implementation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

This review paper highlights the major advances investigating the roles of glucose dependent insulinotropic polypeptide and its receptors in glucose metabolism and their potential use in management of type 2 diabetes mellitus. It also focusses on the role of dipeptidyl peptidase-4 inhibitors in the treatment of this disease. This study discussed the recent therapeutic development which have occurred in this field, and also covering the evolvement of the potential treatments for diabetes which can be discovered and implemented in the near future to design an effective therapy for diabetes and prediabetes., (Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Aim: This study was done to illustrate the clinical and biochemical effects of ethinyl estradiol-cyproterone acetate (EE-AC) and metformin in this disease., Methods: This was a randomized control trial study, done on twenty-six female patients already diagnosed as cases of PCOS. Participants were divided into two study groups: group one (Group 1), received metformin of 500mg twice daily and the second group (Group 2), was given ethinyl estradiol-cyproterone acetate for 21 consecutive days followed by 7 days drug-free. The course of the treatment for both groups was continued for three consecutive months., Results: Group 1 showed a statistical significant increase in serum high density lipoprotein cholesterol (HDL-C) levels (P=0.006) and a decrease in the level of triglyceride (TG) (P=0.006). In addition, Group 1 had a significant reduction in the levels of very density lipoprotein cholesterol (VLDL-C) (P=0.006). Group 2 had a significant increase in serum TG levels (P=0.01), associated with a significant decrease in serum LDL-C (P=0.04). Serum testosterone was significantly reduced in group 1 (P=0.038). This was associated with an improvement in glucose tolerance test (GTT) and BMI in the same group (group 1). Group 2, had an improvement in the menstrual cycle control; hirsutism and acne., Conclusion: This study showed that metformin treatment is beneficial in improving serum lipids; glucose homeostasis and BMI, however, the ethinyl estradiol-cyproterone acetate is superior in improving the clinical manifestation of patients with PCOS, including menstrual cycle regulation, hyperandrogenic state., (Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: This study compared acute and late effect of single-bout endurance training (ET) and high-intensity interval training (HIIT) on the plasma levels of four inflammatory cytokines and C-reactive protein and insulin-like growth factor 1., Design: Cohort study with repeated-measures design., Methods: Seven healthy untrained volunteers completed a single bout of ET and HIIT on a cycle ergometer. ET and HIIT sessions were held in random order and at least 7 days apart. Blood was drawn before the interventions and 30 min and 2 days after the training sessions. Plasma samples were analyzed with ELISA for the interleukins (IL), IL-1β, IL-6, and IL-10, monocyte chemoattractant protein-1 (MCP-1), insulin growth factor 1 (IGF-1), and C-reactive protein (CRP). Statistical analysis was with Wilcoxon signed-rank tests., Results: ET led to both a significant acute and long-term inflammatory response with a significant decrease at 30 minutes after exercise in the IL-6/IL-10 ratio (-20%; p = 0.047) and a decrease of MCP-1 (-17.9%; p = 0.03)., Conclusion: This study demonstrates that ET affects the inflammatory response more adversely at 30 minutes after exercise compared to HIIT. However, this is compensated by a significant decrease in MCP-1 at two days associated with a reduced risk of atherosclerosis.

Objectives: Studies have shown that people with type 2 diabetes mellitus (T2DM) may develop atherosclerosis due to the disturbance in oxidative control and progressive dyslipidemia. Our study aimed to highlight the benefits of simvastatin treatment in improving serum lipids and reducing oxidative damage in patients with T2DM., Methods: Our randomized control trial included 56 patients with T2DM and dyslipidemia. The participants were on glibenclamide (5mg/day) during the period of the study. The patients were divided into two study groups (groups 1 and 2). Group 1 was the control group and consisted of 31 patients. Group 2 consisted of 25 participants, who were given simvastatin 20mg tablet once daily for 12 weeks. The control group did not receive simvastatin. Both groups were followed-up for measurement of blood pressure, pulse rate, serum lipids, and parameters of oxidative stress., Results: The simvastatin treated group showed a significant improvement with reduced erythrocyte glutathione compared to the control group (p<0.001). This was also associated with a significant reduction in erythrocyte malondialdehyde in the simvastatin treated group compared to the control group (p<0.001). Serum lipids reflected a similar improvement in the levels of erythrocyte malondialdehyde., Conclusion: Our study highlights the beneficial role of simvastatin in improving the degree of oxidative stress in patients with T2DM through its effects on serum lipids and lipid peroxidation.

Objectives: This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes., Design and Methods: Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects., Results: While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant., Conclusions: The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings., (Copyright © 2015. Published by Elsevier Inc.)

Background: Copper (Cu) is essential both for its role in antioxidant enzymes, like Cu/zinc (Zn) superoxide dismutase (SOD) and ceruloplasmin, as well as its role in lysyl oxidase, essential for the strength and integrity of the heart and blood vessels. With such a central role in cardiovascular health, Cu has been generally overlooked in the debate over improving our cardiovascular health. Cu deficiency has produced many of the same abnormalities present in cardiovascular disease. It seems almost certain that Cu plays a large role in the development of this killer disease, not because of its excess in the diet, but rather its deficiency., Aim: This study was undertaken to investigate the cardiovascular effects of Cu deficiency on the activity of SOD in patients with type 2 diabetes mellitus (T2DM) with and without diabetic nephropathy., Materials and Methods: Fifty-five patients with T2DM were recruited in this study which were divided into two subgroups based on the presence of microalbuminuria, the first group (microal buminuric group, n = 31) had a microalbuminuria between 30 and 299 μg/mg. The second group (normoal buminuric group, n = 29) had an albumin level less than 30 μg/mg. The two diabetic groups were compared to the control group (n = 37)., Results: The results of our study showed a significant reduction in the levels of SOD enzyme associated with an increased urinary Cu excretion in microalbuminuric group compared to the control group at P < 0.05., Conclusions: The current study illustrates that the regulation of the blood concentrations of Cu may be a potential therapeutic target for prevention and treatment of diabetic nephropathy.

Background: The role of triglycerides in early preclinical atherosclerosis is controversial. Antioxidant markers may be associated with triglyceride levels in early preclinical atherosclerosis especially when fasting plasma glucose is raised., Methods: This cross-sectional study included 127 participants attending the Diabetes Screening Clinic, Charles Sturt University, Australia., Results: Serum 8-hydroxy-2-deoxy-guanosine (8-OHdG) was significantly greater in the impaired fasting glucose (IFG) group compared with the control group (536.7 pg/ml ± 249.8 versus 171.4 pg/ml ± 96.9, respectively). The increase in 8-OHdG was associated with a mildly non-significant elevation in low-density lipoprotein level (3.2 ± 1.1 mmol/l) and a poor level of high-density lipoprotein (1.31 ± 0.3 mmol/l) in the IFG group. However, a significant increase in triglycerides (1.6 ± 0.97 mmol/l; P < 0.05) in the IFG group was observed. Erythrocyte reduced glutathione (GSH) levels in the IFG group, although increased, were also not significantly different to control., Conclusion: A significant increase in 8-OHdG is associated with increased levels of triglycerides in the absence of significant changes in reduced GSH and normal levels of cholesterol in the IFG cohort, suggesting that oxidative stress may be present and indicative of subclinical atherosclerosis.

Objective: This study illustrates the relationship between oxidative DNA damage and obesity in patients with prediabetes and type 2 diabetes compared with controls., Design and Methods: Participants attended the School of Community Health, Diabetes Screening Clinic, Charles Sturt University, Australia, between February 2006 and June 2008. A total of 162 participants (35 type 2 diabetic patients; eight prediabetic subjects; and 119 age-, gender-, and weight-matched controls) were investigated. All patients were selected on clinical grounds., Results: Serum 8-hydroxy 2'-deoxy-guanosine (8-OHdG) level was significantly greater in the prediabetic subjects (671.3±140 pg/ml) compared with controls (210.1±166 pg/ml; P<0.01). The diabetic group (1979.6±1209 pg/ml) had the highest level of 8-OHdG. There was a significant increase in serum 8-OHdG in obese subjects (848.5±103 pg/ml; P<0.001) and overweight subjects (724±102 pg/ml; P=0.005) compared with the lean subjects (196.5±327 pg/ml)., Conclusion: Our results indicate that serum 8-OHdG is increased already in prediabetes suggesting oxidative DNA damage to be present with minor elevation of blood glucose levels (BGLs). The statistically significant positive correlation between serum 8-OHdG and body mass index in the diabetic group indicates that obesity has an additive effect to increased BGL contributing to oxidative DNA damage.

Background: Rising levels of oxidative stress play an important role in the pathogenesis of type 2 diabetes mellitus. Therefore, we investigated the serum level of 8-hydroxy-2-deoxy-guanosine (8-OHdG) as an early oxidative stress marker in patients with prediabetes and with type 2 diabetes mellitus., Subjects and Methods: Convenience sampling from people attending a diabetes screening clinic. Participants at the rural diabetes screening clinic had their medical history recorded as well as body mass index, blood glucose, cholesterol, glutathione, malondialdehyde, fasting blood glucose and 8-OHdG measured. Statistical analysis was performed using ANOVA followed by Sheffe posthoc test for between-group differences., Results: The 8-OHdG level was significantly greater in the prediabetes (516.5 +/- 260 pg/ml) compared to control group (177.8 +/- 91 pg/ml; P < 0.01). The diabetes group (1926.9 +/- 1197 pg/ml) had the highest level of 8-OHdG, being approximately four times greater compared to the prediabetes group (P < 0.001). No significant change in the cholesterol profile, MDA level indicative of lipid peroxidation and antioxidant activity as measured by erythrocyte reduced glutathione was observed in the prediabetes group compared to the control group (P > 0.05)., Conclusions: 8-OHdG levels in both the prediabetes and diabetes group were increased from control values suggesting a role for 8-OHdG as an early disease marker that may be more sensitive compared to cholesterol, MDA and erythrocyte reduced glutathione levels, which were within normal limits. This is of clinical significance as 8-OHdG is a strong indicator of oxidative stress related DNA damage within blood vessel walls and other tissue that increases the risk of cardiovascular disease.