Analysis of Citrus Bioflavonoid Content and Dipeptidyl Peptidase-4 Inhibitory Potential of Commercially Available Supplements.

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.

Genetic polymorphism of angiotensin converting enzyme and angiotensin II type 1 receptors and their impact on the outcome of acute coronary syndrome.

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).

Genetic Polymorphism of Angiotensin II Type 1 Receptors and Their Effect on the Clinical Outcome of Captopril Treatment in Arab Iraqi Patients with Acute Coronary Syndrome (Mid Euphrates).

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.

Minimal effects of reduced teaching hours on undergraduate medical student learning outcomes and course evaluations.

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.

The Nephroprotective Effect of Lycopene on Renal Ischemic Reperfusion Injury: A Mouse Model.

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).

Impact of letrozole versus clomiphene citrate on endometrial receptivity in Iraqi women with polycystic ovarian syndrome.

WHAT IS KNOWN AND OBJECTIVES: Letrozole is widely known for its use as an ovulation inductor. This study aims to investigate the effects of letrozole and clomiphene citrate in females with polycystic ovarian syndrome. METHODS: This is a randomized non-blinded controlled trial study that included 80 infertile females with polycystic ovarian syndrome receiving a standard dose of either clomiphene citrate or letrozole on day 2 of the cycle. An ultrasound was done to examine growth of the follicle, endometrial thickness on days 12-13, and a Doppler study to measure resistance index (RI), pulsatility index and ratio of systolic/diastolic velocity. RESULTS AND DISCUSSION: The mean levels of dominant follicle and oestradiol were significantly higher in the clomiphene citrate group than in the letrozole group. The letrozole group had a significantly greater endometrial thickness than the clomiphene citrate group. The resistance index and pulsatility index were lower in the letrozole group and in pregnant women than in the clomiphene citrate group and the non-pregnant group. WHAT IS NEW AND CONCLUSION: The use of letrozole for ovulation induction in polycystic ovarian syndrome patients has a better effect on endometrial receptivity markers when compared to clomiphene citrate.

Reno-protective effects of TAK-242 on acute kidney injury in a rat model.

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.

Expression of ZO1, vimentin, pan-cadherin and AGTR1 in tanycyte-like cells of the sulcus medianus organum.

Tanycytes are a specialized ependymal lining of brain ventricles with exceptional features of having long basal processes and junctional complexes between cell bodies. These tanycytes are present at the regions of circumventricular organs (CVOs) which possess common morphological and functional features enabling them to be described as the brain windows where the barrier systems have special properties. Previous studies detailed seven of these CVOs but little information is available regarding another putative site at the rostral part of the median sulcus of the 4th ventricle, or the sulcus medianus organum (SMO). Here we performed a pilot immunohistochemical study to support earlier observations suggesting the SMO as a novel CVO. We labeled rat brain with ZO1, vimentin, pan-cadherin and angiotensin II type 1 receptors markers which showed a morphologically distinct population of cells at the region of the SMO similar to tanycytes present in the median eminence, a known CVO. These cells had basal processes reaching the deeply seated blood vessels while the caudal part of the median sulcus did not show similar long cellular extensions. We concluded that tanycyte-like cells are present in the SMO in a pattern resembling that of other CVOs where the strategic location of the SMO is probably for signal integration between brainstem nuclei and the rostrally located neuronal centers.

Citrus bioflavonoids dipeptidyl peptidase-4 inhibition compared with gliptin antidiabetic medications.

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 IC50 values ranging from 485 µM (rutin) to 5700 µM (hesperitin and eriodictyol). Similarly, the flavonoid supplements had IC50 values of 16.9 mg/mL (EN), 3.44 mg/mL (SB) and 2.72 mg/mL (CB). These values compare with gliptin IC50 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.

Acute-Phase Inflammatory Response to Single-Bout HIIT and Endurance Training: A Comparative Study.

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-1ß, 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.

Reduced Insulin Resistance and Oxidative Stress in a Mouse Model of Metabolic Syndrome following Twelve Weeks of Citrus Bioflavonoid Hesperidin Supplementation: A Dose-Response Study.

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.

A systematic review exploring the mechanisms by which citrus bioflavonoid supplementation benefits blood glucose levels and metabolic complications in type 2 diabetes mellitus.

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.

Oridonin supplementation in rabbits may help to improve the outcome of induced atherosclerosis via autophagy induction.

BACKGROUND AND AIM: Inflammation plays a crucial role in the development of atherosclerotic plague. Oridonin is the major active ingredient of the traditional Chinese medicinal herb Rabdosia rubescens. It is a natural terpenoids that is known as a strong anti-inflammatory supplement by acting as a potent inhibitor of the TXNIP/NLRP3 pathway. Hence, it can reduce the severity of inflammation and improve the outcome of atherosclerotic changes. This study aims to evaluate the anti-inflammatory effects of oridonin in the progression of atherosclerotic plague in rabbits. METHODS: Sixty-three male rabbits were included. The rabbits were randomly assigned to one of the three study groups (21 rabbits in each group), normal control diet (NC) fed normal diet for 8 weeks, atherogenic control (AC) fed atherogenic diet (2% cholesterol-enriched diet) for 8 weeks, and oridonin treated group (OT) fed atherogenic diet (2% cholesterol-enriched diet) with oridonin (purity 94%, Sigma-Aldrich, USA) at 20 mg/kg orally daily for 8 weeks. After the end of the study, blood and tissue samples were collected for analysis of various markers of inflammation and atherosclerotic plaque progression. RESULTS: Serum lipids showed a statistically significant improvement in terms of reduction in total cholesterol and low-density lipoprotein (LDL) in the OT group compared to the AC group. This was associated with a significant reduction in serum F2-isoprostane (marker of inflammation) and LC3B (marker of tissue autophagy) between the OT group compared to the AC group. There was also a significant reduction in NLRP3 inflammasome RNA expression in OT group, P<0.001. CONCLUSIONS: In animal model, with atherogenic diet, oridonin supplementation can significantly improve the outcome of atherosclerosis by its strong anti-inflammatory action.

Correlation of serum 1,25-dihydroxycholecalciferol with the incidence of primary open-angle glaucoma: A cross-sectional study on patients with chronic illnesses.

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.

Association of Toll-like receptors 4 (TLR-4) gene expression and polymorphisms in patients with severe asthma.

Innate immunity plays a central role in the pathogenesis of severe asthma, and it is closely linked to elevated IgE and Toll-like receptor 4 (TLR-4) levels. However, there is a scarcity of information about the association of the TLR-4 receptor polymorphism in the pathogenesis of severe asthma. This study highlights the level of gene expression of different alleles in asthmatic patients compared to healthy control individuals. This was a randomized control trial, which included 150 patients with asthma (with high serum levels of IgE) with a matching 150 healthy control individuals. Participants had a series of blood tests to measure various immune parameters: interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), intercellular adhesion molecule-1 (ICAM1) and detect allele type and gene expression of the TLR-4 gene. Patients with asthma had significantly higher levels of IL-8 when compared to the healthy control participants. In addition, in the rs91 genotyping, there were significant differences in the levels of IL-8 and TNF between CC and TT genotyping. While in rs90 TLR-4, TNF levels were significantly higher in AA vs. AG and GG genotypes among the asthmatic patients when compared to the control group. The results showed that in TLR-4, rs4986791 were significantly associated with asthma risk. Polymorphisms in TLRs play essential roles in asthma.

Twelve-Week Mediterranean Diet Intervention Increases Citrus Bioflavonoid Levels and Reduces Inflammation in People with Type 2 Diabetes Mellitus.

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.

Phytosterol supplements do not inhibit dipeptidyl peptidase-4.

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, ß-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; ß-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 ß-sitosterol had an IC50 > 50 mg/ml (maximum tested concentration) and the Thompson's Cholesterol Manager® and Mega Strength Beta Sitosterol® supplements gave an IC50 > 100 mg/ml (maximum tested concentration). Blackmores Cholesterol Health® gave an IC50 value of 40 mg/ml which was attributed to ß-carotene content. CONCLUSIONS: Phytosterol supplements do not appear to offer any anti-diabetic activity potential via pathways that involve the inhibition of DPP-4.

Correlation of CYP2D6 allelic polymorphism to outcome of acute coronary syndrome in mid-Euphrates Iraqi patients on metoprolol therapy.

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.

Assessing urinary levels of IL-18, NGAL and albumin creatinine ratio in patients with diabetic nephropathy.

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.

The association of the common fat mass and obesity associated gene polymorphisms with type 2 diabetes in obese Iraqi population.

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.