Role of NQO1 Gene Involvement and Susceptibility of T2DM Among Saudi Arabia Population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia and is a significant contributor to the development and progression of diabetes. Oxidative stress has been linked to several symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, the present research aimed to evaluate the genetic abnormality of NQO1 (rs1800566, C609T) gene polymorphism, expression, and vitamin-D level assessment among Type 2 diabetes mellitus (T2DM) patients. The study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy controls. Total RNA was extracted from the whole blood using the TRIzol method, and further cDNA was synthesized, and expression was evaluated. There is a significant difference in NQO1 (rs1800566, C609T) genotype distribution among the T2DM patients and healthy controls (p = 0.04). Compared with the NQO1 CC wild-type genotype, the NQO1 CT heterozygous genotype had an odds ratio of 1.96 (1.08-3.55), and the NQO1 TT mutant type genotype had an odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p < 0.0001) and homozygous mutant TT genotype (p = 0.0004), compared with homozygous wild-type CC genotype. NQO1 mRNA expression level was also compared with vitamin D levels among the T2DM patients. T2DM patients with vitamin D deficiency had 1.83-fold NQO1 mRNA expression, while vitamin D insufficient and sufficient T2DM cases had 3.31-fold (p < 0.0001) and 3.70-fold (p < 0.0001) NQO1 mRNA expression. It was concluded that NQO1 (rs1800566, C609T) CT and TT genotypes played a significant role in the worseness of type II diabetes mellitus, and decreased expression of NQO1 mRNA expression could be an essential factor for disease worseness as well as hypermethylation could be a factor for reduced expression leading to disease severity. The decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype associated with vitamin D deficiency may contribute to disease progression.

Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100 mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

Phytocompound screening, antioxidant activity and molecular docking studies of pomegranate seed: a preventive approach for SARS-CoV-2 pathogenesis.

A global hazard to public health has been generated by the coronavirus infection 2019 (COVID-19), which is spreading quickly. Pomegranate is a strong source of antioxidants and has demonstrated a number of pharmacological characteristics. This work was aimed to analyze the phytochemicals present in ethanolic pomegranate seed extract (PSE) and their in vitro antioxidant potential and further in-silico evaluation for antiviral potential against crystal structure of two nucleocapsid proteins i.e., N-terminal RNA binding domain (NRBD) and C-terminal Domain (CTD) of SARS-CoV-2. The bioactive components from ethanolic extract of PSE were assessed by gas chromatography-mass spectroscopy (GC-MS). Free radical scavenging activity of PSE was determined using DPPH dye. Molecular docking was executed through the Glide module of Maestro software. Lipinski's 5 rule was applied for drug-likeness characteristics using cheminformatics Molinspiration software while OSIRIS Data Warrior V5.5.0 was used to predict possible toxicological characteristics of components. Thirty-two phytocomponents was detected in PSE by GC-MS technique. Free radical scavenging assay revealed the high antioxidant capacity of PSE. Docking analysis showed that twenty phytocomponents from PSE exhibited good binding affinity (Docking score ≥ - 1.0 kcal/mol) towards NRBD and CTD nucleocapsid protein. This result increases the possibility that the top 20 hits could prevent the spread of SARS-CoV-2 by concentrating on both nucleocapsid proteins. Moreover, molecular dynamics (MD) simulation using GROMACS was used to check their binding efficacy and internal dynamics of top complexes with the lowest docking scores. The metrics root mean square deviation (RMSD), root mean square fluctuation (RMSF), intermolecular hydrogen bonding (H-bonds) and radius of gyration (Rg) revealed that the lead phytochemicals form an energetically stable complex with the target protein. Majority of the phytoconstituents exhibited drug-likeness with non-tumorigenic properties. Thus, the PSE phytoconstituents could be useful source of drug or nutraceutical development in SARS-CoV-2 pathogenesis.

Crosstalk Between Aging, Circadian Rhythm, and Melatonin.

Circadian rhythms (CRs) are 24-hour periodic oscillations governed by an endogenous circadian pacemaker located in the suprachiasmatic nucleus (SCN), which organizes the physiology and behavior of organisms. Circadian rhythm disruption (CRD) is also indicative of the aging process. In mammals, melatonin is primarily synthesized in the pineal gland and participates in a variety of multifaceted intracellular signaling networks and has been shown to synchronize CRs. Endogenous melatonin synthesis and its release tend to decrease progressively with advancing age. Older individuals experience frequent CR disruption, which hastens the process of aging. A profound understanding of the relationship between CRs and aging has the potential to improve existing treatments and facilitate development of novel chronotherapies that target age-related disorders. This review article aims to examine the circadian regulatory mechanisms in which melatonin plays a key role in signaling. We describe the basic architecture of the molecular circadian clock and its functional decline with age in detail. Furthermore, we discuss the role of melatonin in regulation of the circadian pacemaker and redox homeostasis during aging. Moreover, we also discuss the protective effect of exogenous melatonin supplementation in age-dependent CR disruption, which sheds light on this pleiotropic molecule and how it can be used as an effective chronotherapeutic medicine.

Exposure to pesticide residues in honey and its potential cancer risk assessment.

Honey is the most recognized natural food by-product derived from flower nectar and the upper aero-digestive tract of the honeybees. Significance of honey for its medicinal importance are well-documented in the world's oldest medical literatures. However, the current urbanization, environmental contaminations and changes in agricultural, as well as apiculture practices has led to various types of contaminations in honey. Among all, pesticide contamination has become one of the major issues worldwide. This review focuses on the recent updates concerning pesticides occurrence in honey, as well as how the repeated use and long-term exposure to honey contaminated with pesticide residues could affect the human physiological functions, possibly leading to the development of various cancers. Our findings suggests that uncontrolled use of pesticides in farming and apiculture practices leads to the occurrence of pesticides residues in honey. Therefore, regular consumption of such honey will pose a serious threat to human health, since most of the pesticides has been reported as potential carcinogens. This review will draw the attention of honey consumers, scientific communities, apiculture farmers, as well as governing bodies to strictly monitor the pesticide usage in floriculture, agriculture as well as other related practices.

Advanced glycation end product signaling and metabolic complications: Dietary approach.

Advanced glycation end products (AGEs) are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions. The modern western diet is full of heat-treated foods that contribute to AGE intake. Foods high in AGEs in the contemporary diet include processed cereal products. Due to industrialization and marketing strategies, restaurant meals are modified rather than being traditionally or conventionally cooked. Fried, grilled, baked, and boiled foods have the greatest AGE levels. Higher AGE-content foods include dry nuts, roasted walnuts, sunflower seeds, fried chicken, bacon, and beef. Animal proteins and processed plant foods contain furosine, acrylamide, heterocyclic amines, and 5-hydroxymethylfurfural. Furosine (2-furoil-methyl-lysine) is an amino acid found in cooked meat products and other processed foods. High concentrations of carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-O are found in heat-treated nonvegetarian foods, peanut butter, and cereal items. Increased plasma levels of AGEs, which are harmful chemicals that lead to age-related diseases and physiological aging, diabetes, and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation. Insulin resistance and hyperglycemia can impact numerous human tissues and organs, leading to long-term difficulties in a number of systems and organs, including the cardiovascular system. Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease, such as ventricular dysfunction. High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure. It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress. All chronic illnesses involve protein, lipid, or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs. Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways. Many of these systems, however, require additional explanation because they are not entirely obvious. This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.

Mercuric Chloride Induced Nephrotoxicity: Ameliorative Effect of Carica papaya Leaves Confirmed by Histopathology, Immunohistochemistry, and Gene Expression Studies.

The present study analyzes the efficacy of the ethanolic extract of C. papaya leaves (ECP) against HgCl2-induced nephrotoxicity. The effects on the biochemical and percentage of body and organ weight against HgCl2-induced nephrotoxicity in female Wistar rats were studied. Wistar rats were divided into five groups with six animals in each group: control, HgCl2 (2.5 mg/kg b.w.), N-acetylcysteine (NAC 180 mg/kg) + HgCl2, ECP (300 mg/kg b.w.) + HgCl2, and ECP (600 mg/kg) + HgCl2 groups. After 28 days of study, animals were sacrificed on the 29th day to harvest the blood and kidneys for further analysis. The effect ECP was analyzed by immunohistochemistry (NGAL) and real-time PCR (KIM-1 and NGAL mRNA) in HgCl2-induced nephrotoxicity. The results revealed that the HgCl2 group showed prominent damage in the proximal tubules and glomerulus of nephrons and enormous expression of NGAL in immunohistochemistry and KIM-1 and NGAL in real-time PCR compared to the control group. The simultaneous pretreatment with NAC (180 mg/kg) and ECP (600 and 300 mg/kg) reduced renal damage and expression of NGAL in immunohistochemistry and KIM-1 and NGAL gene in real-time PCR. This study attests to the nephroprotective effect of ECP against HgCl2-induced toxicity.

Comparison of TCN-2 (776C>G) Gene Polymorphism and Vitamin B12 Status with Different Body Mass Index among Saudi Adults.

BACKGROUND: Overweight and obesity (OO) are significant public health issues, and many elements, including genetics, epigenetics, sedentary lifestyle, comorbid conditions, psychological and environmental pressures, have been linked to OO. More than 2 billion people are presently impacted by the global obesity epidemic, which is still advancing relentlessly. It is a significant public health concern and a major contributor to healthcare costs, because it increases the chance of developing conditions such as heart disease, stroke, type 2 diabetes, and chronic kidney disease (CKD). Using the ranges of 18.5-25 for normality, 25-30 for overweight, and 30 for obesity, BMI (in kg/m2) is used to identify obesity. Vitamin deficiency is one of the causative factors associated with the increasing trend of obesity. Altered vitamin B12 status is a multifactorial trait; changes in B12 status are produced by several single nucleotide polymorphisms (SNPs) in various genes that interact with the environment. They also support coordinated efforts to alter the built environment that is causing the obesity pandemic. Therefore, the present study aimed to evaluate the TCN-2 (776C>G) gene alteration and vitamin B12 levels with respect to different body mass index, as well as associating BMI with other biochemical parameters. METHODS: 250 individuals were involved in the study; among them, 100 were in the healthy weight range category (BMI: 18.5 to <25 kg/m2), 100 were overweight (BMI: 25.0 to <30 kg/m2), and 50 were obese (BMI: >30 kg/m2). Participants visited during the screening program were subjected to blood pressure measurement, and further peripheral blood samples were drawn from all the participants in plain as well as in EDTA vials for biochemical (lipid profile and vitamin B12 level) analysis and single nucleotide polymorphism studies. Extracted DNA from whole blood collected in EDTA vials using kit protocol was used for genotyping by PCR-RFLP. RESULTS: The levels of systolic (p < 0.0001) and diastolic blood pressures (p < 0.0001), HDL (p < 0.0001), LDL (p = 0.04), TG (p < 0.0001), cholesterol (p < 0.0001), and VLDL (p < 0.0001) showed significant differences between healthy controls, overweight, and obese groups. The healthy control TCN-2 (776C>G) genotypes were compared with those of overweight and obese participants, and compared to the healthy controls it was observed that overweight (p = 0.01) and obese (p = 0.002) subjects had significant differences in TCN-2 (776C>G) genotypes. For genotypes CG and GG, the odds ratio was 1.61 (0.87-2.95; p = 0.12), and 3.81 (1.47-9.88; p = 0.005) for overweight participants, respectively, and obese participants' calculated odds ratios were 2.49 (1.16-5.36; p = 0.01) and 5.79 (1.93-17.35; p = 0.001), respectively. The relative risk for genotypes CG and GG, was 1.25 (0.93-1.68; p = 0.12), 2.17 (1.12-4.17; p = 0.02) for overweight participants, while the obese participants' calculated relative risks were 1.31 (1.03-1.68; p = 0.01) and 2.02 (1.12-3.65; p = 0.001), respectively. Vitamin B12 levels were analyzed, and it was observed that a significant difference existed among overweight (305.5 pmol/L, p < 0.0001) and obese patients (229 pmol/L, p < 0.0001), respectively, as compared to healthy controls (385.5 pmol/L). Correlation analysis showed a significant association of vitamin B12 level with TG, cholesterol and VLDL; it showed a negative correlation, suggesting that decreases in B12 levels may impact the lipid profile. CONCLUSION: The study concluded that a predisposition to the GG genotype of TCN-2 gene polymorphism (776C>G) may increase susceptibility to obesity and the related complications, and higher odds and relative risk for the GG genotype may increase the risk of having obesity and further related complications. Lower vitamin B12 levels were linked with obesity and overweight, and impaired lipid parameters suggested that lower vitamin B12 may impact the altered lipid profile.

Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint.

The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing.

Moringa oleifera leaf extract induces osteogenic-like differentiation of human osteosarcoma SaOS2 cells.

Introduction: Moringa oleifera is known as a 'natural nutrition of the tropics' because it provides vital nutritional supplements and a variety of pharmacological benefits. The focus of this study was to elucidate the dose dependent effects of Moringa oleifera leaf (MOL) extract on the growth of the human osteoblast-like osteosarcoma SaOS-2 cell line and primary osteoblast cells. Methods: Trypan blue & tetrazolium assay, intracellular ROS generation, chromatin condensation, cell cycle analysis, alkaline phosphatase (ALP), mineralization, and osteogenic gene expression were tested on both treated and untreated osteosarcoma SaOS-2 cells. Results: As revealed by cell viability assay, growth activity was observed at concentrations 25 and 50 µg/mL of MOL extract, whereas 100 and 200 µg/mL doses decreased the proliferation activity, resulting in ROS production and chromatin condensation. Cell cycle study revealed that MOL extract at 50 and 100 µg/mL concentrations arrested the cells in the G2/M phase. Low doses increased the ALP levels, mineralization, and expression of the bone morphogenetic protein 2 (BMP2) and runt-related transcription factor 2 (Runx2) genes in osteoblast-like SaOS-2 cells, however, high doses inhibited the proliferation properties of MOL extract. Through AutoDock Vina and iGEMDOCK 2.1, the interaction of active components of MOL, such as ß-sitosterol, quercetin and kaempferol, with BMP2 and Runx2 proteins revealed a reasonable binding affinity. Moreover, these components did not show any Lipinski's rule of five violation and showed predictable pharmacokinetic properties. Conclusion: The results of the biphasic dose-response of MOL extract on the growth activity of osteoblast-like SaOS-2 cells and in silico binding interface, may provide a therapeutic and/or preventive implication in prospective drug development.

Biosynthesized Silver Nanoparticles from Eruca sativa Miller Leaf Extract Exhibits Antibacterial, Antioxidant, Anti-Quorum-Sensing, Antibiofilm, and Anti-Metastatic Activities.

Worldwide, the primary problem today is the proliferation of cancer and secondary bacterial infections caused by biofilms, as they are the principal causes of death due to the lack of effective drugs. A great deal of biological activities of silver nanoparticles (AgNPs) have made them a brilliant choice for the development of new drugs in recent years. The present study was conducted to evaluate the anticancer, antibacterial, anti-QS, and antibiofilm effects of AgNPs synthesized from Eruca sativa (E. sativa) leaf extract. The ultraviolet-visible (UV-Vis) spectra showed a peak of surface plasmon resonance at 424 nm λmax, which corresponded to AgNP formation. The Fourier transform infrared spectroscopy (FT-IR) confirmed that biological moieties are involved for the development of AgNPs. Moreover, transmission electron microscopy (TEM) analyses confirmed the spherical shape and uniform size (8.11 to 15 nm) of the AgNPs. In human lung cancer cells (A549), the anticancer potential of AgNPs was examined by the MTT [3-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scratch assay, and invasion assay. The results indicated that AgNPs inhibit the migration of A549 cells. The synthesized AgNPs showed MIC values of 12.5 µg/mL against Chromobacterium violaceum (C. violaceum) and 25 µg/mL against Pseudomonas aeruginosa (P. aeruginosa), which demonstrated their antibacterial abilities. Biological compounds that disable the QS system are being investigated as potential strategies for preventing bacterial infections. Thus, we analyzed the potential effectiveness of synthesized AgNPs in inhibiting QS-regulated virulence factors and biofilm formation in both strains of bacteria. In C. violaceum, the synthesized AgNPs significantly inhibited both violacein (85.18% at 1/2 × MIC) and acyl homoserine lactone (78.76% at 1/2 × MIC). QS inhibitory activity was also demonstrated in P. aeruginosa at a sub-MIC concentration (1/2 × MIC) by a reduction in pyocyanin activity (68.83%), total protease (68.50%), LasA activity (63.91%), and LasB activity (56.40%). Additionally, the exopolysaccharide production was significantly reduced in both C. violaceum (65.79% at 1/2 × MIC) and P. aeruginosa (57.65% at 1/2 × MIC). The formation of biofilm was also significantly inhibited at 1/2 × MIC in C. violaceum (76.49%) and in P. aeruginosa (65.31%). Moreover, a GC-MS analysis confirmed the presence of different classes of bioactive phytochemical constituents present in the leaf extract of E. sativa. On the basis of our results, we conclude that biologically synthesized AgNPs showed numerous multifunctional properties and have the potential to be used against human cancer and bacterial biofilm-related infections.

Chitosan-modified nanocarriers as carriers for anticancer drug delivery: Promises and hurdles.

With the advent of drug delivery, various polymeric materials are being explored to fabricate numerous nanocarriers. Each polymer is associated with a few characteristics attributes which further facilitate its usage in drug delivery. One such polymer is chitosan (CS), which is extensively employed to deliver a variety of drugs to various targets, especially to cancer cells. The desired properties like biological origin, bio-adhesive, biocompatibility, the scope of chemical modification, biodegradability and controlled drug release make it a highly rough after polymer in pharmaceutical nanotechnology. The present review attempts to compile various chemical modifications on CS and showcase the outcomes of the derived nanocarriers, especially in cancer chemotherapy and drug delivery.

Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East.

Dietary arsenic (As) contamination is a major public health issue. In the Middle East, the food supply relies primarily on the import of food commodities. Among different age groups the main source of As exposure is grains and grain-based food products, particularly rice and rice-based dietary products. Rice and rice products are a rich source of core macronutrients and act as a chief energy source across the world. The rate of rice consumption ranges from 250 to 650 g per day per person in South East Asian countries. The source of carbohydrates through rice is one of the leading causes of human As exposure. The Gulf population consumes primarily rice and ready-to-eat cereals as a large proportion of their meals. Exposure to arsenic leads to an increased risk of non-communicable diseases such as dysbiosis, obesity, metabolic syndrome, diabetes, chronic kidney disease, chronic heart disease, cancer, and maternal and fetal complications. The impact of arsenic-containing food items and their exposure on health outcomes are different among different age groups. In the Middle East countries, neurological deficit disorder (NDD) and autism spectrum disorder (ASD) cases are alarming issues. Arsenic exposure might be a causative factor that should be assessed by screening the population and regulatory bodies rechecking the limits of As among all age groups. Our goals for this review are to outline the source and distribution of arsenic in various foods and water and summarize the health complications linked with arsenic toxicity along with identified modifiers that add heterogeneity in biological responses and suggest improvements for multi-disciplinary interventions to minimize the global influence of arsenic. The development and validation of diverse analytical techniques to evaluate the toxic levels of different As contaminants in our food products is the need of the hour. Furthermore, standard parameters and guidelines for As-containing foods should be developed and implemented.

Long-term outcomes post chronic total occlusion intervention-implications of completeness of revascularization.

BACKGROUND: Long term clinical outcomes post chronic total occlusion (CTO) intervention may depend not only on CTO success/failure alone but also on Completeness of revascularization. OBJECTIVES: To determine long term outcomes post CTO intervention and relate them to both success versus failure and Complete Revascularization (CR) versus Incomplete Revascularization (IR). METHODS: Consecutive patients taken up for CTO intervention with at-least one CTO vessel between Jan 2006 to Dec 2015 were included. Clinical, procedural and follow up details were recorded in a pre-specified custom made software. Primary endpoint of the study was survival free of major adverse event individual, death, myocardial infarction (MI), repeat revascularisation (percutaneous coronary intervention [PCI], or coronary artery bypass grafting (CABG) and recurrent or continued angina. Each individual adverse event was considered as a secondary end point. RESULTS: A total of 632 patients were enrolled in study with follow up data available in 549 (86%) constituting the study group with 490 (89.3%) success and 59 (11.7%) failure. Complete revascularization (CR) was obtained in 410 (74.7%). Follow up was median 2.9 years with inter-quartile range 1.1-4.8 years. Kaplan Meier survival analysis showed a better EFS with both CTO success versus failure (P = 0.03)and CR versus IR (P = 0.017). Individual adverse outcomes however were not significantly different in CTO success versus failure group but significantly better when analyzed with respect to CR versus IR including death (P = 0.049) and recurrent angina (P = 0.024). Repeat intervention and MI were not different by either analysis. CONCLUSIONS: Successful CTO PCI results in a better long term event free survival but the difference between the groups is more if analyzed with respect to completeness of revascularization rather than CTO success/failure alone.

A weighted angiographic scoring model (W-CTO score) to predict success of antegrade wire crossing in chronic total occlusion: analysis from a single centre.

Aims: The aim of this study was to derive a weighted score model predicting success/failure of antegrade wire crossing in chronic total occlusion (CTO) percutaneous coronary intervention (PCI). Methods and results: Four hundred and four consecutive CTO cases (408 lesions) undergoing CTO-PCI between January 2009 and March 2015 were included. Data were divided into two sets, namely "derivation" and "validation", in a 70:30 ratio. The score was derived using multivariate analysis to identify independent predictors of wire crossing failure from the derivation set (n=285 lesions) and validated on the remaining 123 lesions (validation set). The overall procedural success rate was 83.6%. Independent predictors of CTO-PCI failure and their contribution to the weighted score were a blunt stump (beta coefficient 2.12), length of occlusion >20 mm (beta coefficient 1.71), presence of calcification (beta coefficient 0.72), presence of tortuosity (beta coefficient 1.06) and collateral with Rentrop grade <2 (beta coefficient 1.06). The respective scores allotted were +2.0, +1.5, +1, +1, +1 (total 6.5), rounding the coefficient to the nearest 0.5. Score values of 0-2, >2-4 and >4 were classified as low, intermediate and high levels of difficulty for CTO-PCI success and were associated with 98%, 74.2%, and 42.5% (p<0.0001), respectively, of antegrade wire crossing success in the derivation set. This was also validated on the validation set with CTO success in the three derived difficulty levels being 100%, 82.4% and 48.4%, respectively. Conclusions: Our weighted angiographic CTO score is a strong predictor of final antegrade wire crossing success and could be used in day-to-day clinical practice of CTO interventions.

The Association Between Small Dense Low Density Lipoprotein and Coronary Artery Disease in North Indian Patients.

Pathogenesis of coronary artery disease (CAD) is multi-factorial and several conventional risk factors have been ascribed; LDL-C being one of the important risk factor. However Indian population studies with established CAD often show LDL levels within normal range in patients with proven CAD. We hypothesized that Small dense low density lipoprotein (sdLDL) being more atherogenic might correlate more strongly to the occurrence and severity of CAD. The aim of the study was to evaluate the association between serum small dense LDL level and angiographically documented coronary artery disease. This is a cross sectional case control study in which sdLDL were measured in 126 patients with CAD and in 64 patients without CAD. Total cholesterol, HDL Cholesterol, LDL cholesterol and triglycerides were measured by standard methods along with other traditional risk factors. Direct quantitative measurement of sdLDL was done by enzymatic analysis. Mean sdLDL level was higher in patients with coronary stenosis than patients without coronary stenosis (16.3 ± 6.8 vs. 10.1 ± 5.7 mg/dL respectively, (p < 0.001). There was significant correlation between mean sdLDL and severity of CAD as assessed by syntax score with mean sdLDL level in low, intermediate and high syntax score being 15.0 ± 5.8, 20.1 ± 6.7 and 22.7 ± 7.3 mg/dL respectively (p value <0.001). A cut off value of 10.02 mg/dL was associated with presence of CAD (95 % CI 0.82-0.93, p < 0.001) using ROC curve. In conclusion Indian patients with established CAD have higher sdLDL levels compared to individuals without CAD despite having comparable LDL levels.

Effect of high-dose zinc supplementation with oral hypoglycemic agents on glycemic control and inflammation in type-2 diabetic nephropathy patients.

OBJECTIVE: The study aims to evaluate the effect of zinc sulfate on markers of glycemic control, lipid profile and inflammation in type-2 diabetes with microalbuminuria patients. MATERIALS AND METHODS: Type-2 diabetes with microalbuminuria patients on oral hypoglycemic agents (OHA) and angiotensin converting enzyme (ACE) inhibitors were selected and divided into 2 groups: One group (n = 27) continued with OHA alone, second group (n = 27) was on OHA and in addition 50 mg elemental zinc as zinc sulphate supplementation for 12 weeks. Fasting, post-prandial blood glucose, glycosylated hemoglobin, lipid profiles, inflammatory marker hs-CRP and urine microalbumin were measured. RESULTS: There were no significant differences in biochemical status among groups at baseline. After receiving zinc, the mean fasting blood glucose (FBS), post-prandial blood glucose (PPBS) and glycosylated hemoglobin (HbA1c) were decreased significantly (P = 0.0001). Significant decrease was observed in TG (P = 0.002) and VLDL-cholesterol (P = 0.002), whereas there was no significant decrease in TC and LDL-cholesterol. The high-density lipoprotein (HDL) cholesterol was significantly (P = 0.0001) increased from baseline. Zinc supplementation had significant effects in decreasing serum hs-CRP from 10.51 ± 1.68 mg/L to 7.75 ± 1.56 mg/L (P = 0.0001) and microalbumin level from 146.87 ± 30.83 mg/day to 80.70 ± 33.99 mg/day (P = 0.0001). There were no significant changes in the levels of all these parameters in OHA group. CONCLUSION: Our results conclude that supplementation of zinc improved the effectiveness of OHA and may be beneficial in decreasing blood glucose, TG, urinary albumin excretion and inflammation in diabetic nephropathy patients and thus reducing the risk of complications.

Lipoprotein (a) Levels in Relation to Severity of Coronary Artery Disease in North Indian Patients.

BACKGROUND: Lipoprotein (a) [Lp (a)] is an established risk marker of coronary artery disease which is independent from other risk factors. OBJECTIVE: The aim was to address the association between Lp (a) and CAD risk in North Indians. To evaluate whether high levels of lipoprotein (a) [Lp (a)] is a predictor of risk and is related to the severity of CAD. MATERIALS AND METHODS: This was a cross-sectional study done on 360 patients presenting with chest pain. Coronary angiography revealed CAD in 270 patients and 90 patients without CAD. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. RESULTS: Lipoprotein (a) 21.0 mg/dL is associated with the presence of coronary lesions (P = 0.0001). A highly significant difference in Lp (a) levels was observed between normal coronaries vs. single-vessel disease, double-and triple-vessel disease ( P < 0.0001). Body mass index (BMI) was significantly raised in CAD group compared to normal coronary. CONCLUSION: Multivariate analysis found that Lp (a) was considered an independent predictor for severity of CAD and Lp (a) levels 21.0 mg/dL are associated with severe patterns of coronary atherosclerosis.

A study of clinical presentation and delays in management of acute myocardial infarction in community.

To assess the medico social demographics of acute myocardial infarction (AMI) in our community we studied 609 patients presenting between January 2008 to December 2008 with a detailed questionnaire in four centres of UP. Medical attention was sought late (> 6 hours) in 316 (51.6%), thrombolysis was obtained in 45.2% (275) and presentation was atypical in 16.3% (99). 36.2% (221) had pre-monitory symptoms of which 68% (150) ignored the same while of 32% (71) who did seek medical attention 47.9% (37) were brushed away as non-cardiac in origin. 20.3% (46/226) of hypertension, 23.2% (43/185) of diabetes and 83.4% (91/109) of hyperlipidaemia was diagnosed post event. We conclude that at least half of patients with AMI do not get definitive therapy, at least one in 10 patients do not have the classical symptoms, reasonable proportion are unaware of their risk factors, and a good majority have pre-monitory symptoms which get overlooked.

Lipoprotein(a) and SYNTAX Score Association with Severity of Coronary Artery Atherosclerosis in North India.

OBJECTIVES: This cross-sectional study investigated the association of lipoprotein(a) [Lp(a)] levels as an atherosclerosis predictor and their relationship to the severity of coronary artery disease (CAD). METHODS: 360 consecutive patients at Sanjay Gandhi Postgraduate Institute of Medical Sciences and King George's Medical University hospitals, Lucknow, North India, with chest pains, CAD symptoms and on lipid-lowering therapy were enrolled between June 2009 and October 2011. Before coronary artery angiography (CAG), a fasting blood sample was assessed for lipid and Lp(a) levels. The synergy between percutaneous coronary intervention with taxus and cardiac surgery (SYNTAX) score was calculated according to the CAG results. Patients were divided into 3 groups based on CAD severity and SYNTAX scores. RESULTS: Angiography revealed CAD in 270 patients. Lp(a) levels were higher in CAD compared to non-CAD patients (48.7 ± 23.8 mg/dl versus 18.9 ± 11.1 mg/dl [P <0.0001]). The levels of Lp(a) were lower in single than in double and triple vessels (39.3 ± 18.4 mg/dl versus 58.0 ± 23.0 mg/dl, and 69.2 ± 24.1 mg/dl, [P <0.05]). Lp(a) levels were significantly higher in severe CAD with SYNTAX score >30 (88.0±24.0 mg/dl). Lp(a) levels correlated significantly with SYNTAX scores (r = 0.70, P <0.0001). CONCLUSION: In this study, Lp(a) levels were positively associated with a patient's SYNTAX score in diseased vessels. Furthermore, an elevated Lp(a) level was a causal, independent risk factor of CAD. Lowering Lp(a) levels would reduce CAD in primary and secondary prevention settings. There is an urgent need to define more precisely which patients to treat and which to target for earlier interventions.