Correlation of Risk Factors with Severity of Diabetic Retinopathy - A Retrospective Study.

Diabetic retinopathy (DR) is a major microvascular complication of diabetes. It is the most common cause of blindness in the working-age population in developed countries. We wanted to analyse the correlation between risk factors of blindness like duration of diabetes, dyslipidaemia, hypertension, HbA1c with severity of diabetic retinopathy in order to design appropriate strategies for prevention and treatment of diabetic retinopathy.METHODSThis was a retrospective study of all diabetic patients with diabetic retinopathy who presented to the eye OPD at KS Hegde Medical Academy from April 1st 2018 to March 31st 2019 that fulfilled the inclusion criteria. A dilated fundus examination was done to note the grade of diabetic retinopathy. The demographic data along with the duration of diabetes, HbA1c values, Cholesterol levels and Blood pressure were documented and correlated with the severity of diabetic retinopathy.RESULTSThe study included 92 patients, of which 63 were males and 29 were females with a mean age of 54.5±2.8 years. We found that there was statistically significant association between the duration of diabetes and HbA1c levels with severity of diabetic retinopathy (p= 0.022 and 0.034 association), whereas there was no statistically significant correlation between blood pressure and cholesterol levels with severity of diabetic retinopathy (p= 0.52 and 0.456 respectively)CONCLUSIONSDiabetic retinopathy showed a male preponderance, with risk factors like duration of diabetes and HbA1c levels having a significant association with the severity of diabetic retinopathy. Therefore, it is essential to have a good systemic control of diabetes with diet and suitable medications. Diabetic retinopathy is a preventable cause of blindness when diagnosed early and screening of diabetic retinopathy must be done in all diabetics to prevent the progression of the disease.

Numerical Study on Low-Density Lipoprotein Transport and Deposition in Carotid Arteries and the Associated Factors / 医用生物力学

Objective To investigate the transport and deposition behaviors of lowdensity lipoproteins (LDL) in the carotid artery and explore their associations with hemodynamic and morphological factors, so as to provide theoretical references for assessing the risk and predisposing regions of atherosclerosis based on the characteristics and associated factors of LDL deposition at the carotid artery wall. Methods Subject-specific computational models of the carotid artery based on medical images from six healthy volunteers were built, and the transport and wall deposition of LDL under pulsatile flow conditions were simulated, and finally the correlations of wall LDL concentration and total area of regions with LDL concentration polarization with flow velocity and morphological parameters of the carotid artery were quantitatively analyzed. Results Regions with significant LDL deposition often appeared in carotid sinus near distal end of the common carotid artery, with the degree and spatial distribution of deposition differing considerably among subjects. The degree of LDL deposition was determined mainly by flow velocity, i.e., the lower the flow velocity was, the higher the degree of LDL deposition and accordingly the larger the area of wall regions with LDL concentration polarization was; whereas the spatial distribution of LDL deposition was significantly affected by morphological characteristics (especially bifurcation eccentricity ratio) of the carotid artery, for example, the distribution patterns could be divided into two typical types (i.e., circular distribution, unilateral distribution) according to bifurcation eccentricity ratio. Conclusions Flow velocity and morphological characteristics of the carotid artery are major factors determining respectively the degree and spatial distribution of LDL deposition, and therefore subject-specifically measuring these parameters will provide useful information for screening individuals at high risk of atherosclerosis or identifying atheroprone regions.

To Study the Association of Cerebrovascular Disease with Metabolic Syndrome in Western Uttar Pradesh

Objective: To Study the association of cerebrovascular disease with metabolic syndrome. Methods: A Total 104 patients were included in this study & investigated for cerebrovascular disease associated with metabolic syndrome or not. A study of presence or absence of metabolic syndrome in cerebrovascular disease was done. P value was calculated by using analysis of variance test (ANOVA) & P value <0.05 was considered as statistically significant. Results: Total 104 patients were included in this study in 72 patients (69.23%) were suffering from metabolic syndrome and 32 patient (30.77%) were not suffering from metabolic syndrome. Most of the patients suffering from cerebrovascular disease associated with metabolic syndrome were of older age groups (61.11%)>61 years. Second most common group was (22.22%) 51-60 years. Other patients of cerebrovascular disease not suffering from metabolic syndrome (56.25%) in 51-60 years followed by (31.25%) in 41-50 years. Amongst the patients suffering from cerebrovascular accident and metabolic syndrome males outnumbered females, although this data is not statistically significant p=0.4. Among the Cerebrovascular accident patient group prevalence was highest therefore raised fasting blood sugar (n=58) (80.55%) and low HDL values (75.2%), whereas it was highest for Hypertension (88.89%). In the cerebrovascular accident group out of total 104 patients 72%(n=72) were suffering from metabolic syndrome and 30.77%(n=32) were not suffering from metabolic syndrome there is positive correlation between metabolic syndrome and cerebrovascular accident .Using Test for equality for proportion (zscore) this data is found to be statistically significant. Conclusion: In cerebrovascular accident group (total patients =104) 67.5%(n=108) were having 3 risk factors, 50%(n=80) were having 4 risk factors and 11.25%(n=18) were having 5 risk factors of metabolic syndrome among the cases .Among the patients suffering from cerebrovascular accident (total patients =104) the prevalence of hypertension was 88.89%(n=64),of low HDL was 75.2%(n=54),of high TGs was 80.55%(n=58),of raised waist circumference was 58.32%(n=42) and of increased fasting blood sugar was 80.55%(n=58) in the case group.

Association between Chronic Periodontitis and Serum Lipid Levels

Hyperlipidemia is a known risk factor for cardiovascular diseases. A common biologic mechanism between systemic diseases, such as cardiovascular diseases, and periodontal diseases has been suggested. The aim of this study is to examine the association between blood lipid profile and periodontitis. Aim: To study the correlation between serum lipid profile and periodontitis. Methods: The levels of serum lipid profile in 60 subjects, 30 with chronic generalized periodontitis based on clinical attachment loss (CAL) constituting the test group and 30 without periodontitis constituting the control group, were measured and compared with each other. Both these groups were free from other systemic illnesses. Statistical Analysis: The mean CAL was positively correlated with serum low-density lipoprotein (LDL) cholesterol (P < 0.01). Results: The mean serum LDL cholesterol (126.62) and total cholesterol (173.32) in periodontitis patients were found to be significantly higher as compared to that of the controls. The mean CAL (5.32 mm) was positively correlated with serum LDL cholesterol. The frequency of persons with pathologic values of LDL cholesterol and total cholesterol was significantly higher in periodontitis patients compared with that of the controls. Conclusion: These results showed that high serum LDL cholesterol and total cholesterol may be associated with periodontitis in otherwise healthy people. However, it is unclear whether periodontitis causes an increase in the levels of serum LDL.

Vascular Endothelial Glycocalyx and Lipoproteins / 医用生物力学

Vascular endothelial cell glycocalyx is a layer of glycoprotein complex located on the surface of endothelial cells, forming a selective permeation barrier on the surface of endothelial cells. In the present review, after a brief introduction of glycocalyx, the relationship between glycocalyx and mass transport under fluid sheer stress (FSS), especially the relationship between glycocalyx and macromolecules such as low density lipoprotein (LDL) has been discussed. This relationship was reflected as following: on the one hand, the thickness and integrity of the glycocalyx affects the concentration polarization of LDL and its transendothelial transport and heparan sulfate proteoglycan (HSPG) participates in the whole process of residual lipoproteins metabolism. On the other hand, ox-LDL, an oxidized product of LDL, destroys heparan sulfate (HS) which is a major component of the endothelial cell glycocalyx. The study on relationship between vascular endothelial glycocalyx and lipoproteins will provide a new clue to elucidate the pathogenesis of atherosclerosis and provide more evidence to view the glycocalyx as a new control target.

CARDIAC AUTONOMIC NEUROPATHY AMONG DIABETIC PATIENTS / Шинэ санаа Шинэ нээлт

Today, there are 382 million people living with diabetes. A further 316 million with impaired glucose tolerance are at high risk from the disease – an alarming number that is set to reach 471 million by 2035. One of the most overlooked of all serious complications of diabetes is cardiovascular autonomic neuropathy (CAN) which encompasses damage to the autonomic nerve fibers that innervate the heart and blood vessels, resulting in abnormalities in heart rate control and vascular dynamics. The present report discusses the clinical manifestations (eg, resting tachycardia, orthostatic hypotension exercise intolerance, intra operative cardiovascular liability, silent myocardial infarction (MI), and increased risk of mortality) in the presence of CAN. The reported prevalence of CAN varies greatly depending on the criteria used to identify CAN and the population studied. CAN prevalence ranges from as low as 2.5% of the primary prevention cohort in the Diabetes Control and Complications Trial (DCCT) to as high as 90% of patients with long-standing type 1 diabetes who were potential candidates for a pancreas transplantation. Objective: The aim of this study was to evaluate the Cardiac Autonomic Neuropathy (CAN) among diabetic patients.This study included patients with T1 DM and 20 patients with T2 DM total (97 male, 86 female) diabetic patients. The CAN diagnosed by 6 clinical tests: Resting Heart Rate (RHR), Expiration : Inspiration (E:I) ratio, Heart rate response to standing (30:15 ratio), Orthostatic hypotension (OH) and Sustained Hand Grip (SHG) using Cardiac Autonomic Neuropathy System Analyzer CAN-504. CAN was indicated at least two of five tests are abnormal.Diabetic patients’ mean age was 48.74±12.74, diabetes duration 7.55±5.72, systolic blood pressure 136.25±22.76mm Hg, diastolic blood pressure 84.82±11.90 mmHg, cholesterol 5.04±1.04mmol/l, triglyceride 2.20±1.24mmol/l, LDL2.64±0.85mmol/l, HDL 1.12±0.41mmol/l, non-HDL 3.71±1.06, cholesterol/HDL ratio 4.70±1.29, HBA1c 10.08±2.39%. Result of RHR resting heart rate test was normal 92%, borderline 0.5% and abnormal 7.1%,Expiration:inspiration(E:I) ratio was normal 72.7%,borderline 13.7% and abnormal 14%, Heart rate response to standing (30:15ratio) was normal 47%,borderline 13.714% and abnormal 39.3%, Valsalva was normal 97.8%,borderline 2.2% and abnormal 0%, Orthostatic hypotension (OH) was normal 66%,borderline 29% abnormal 6% and Sustained hand grip(SHG) test was normal 4.9%,borderline 9%, and abnormal 87.8%.Number of abnormal cardiac autonomic neuropathy test results 2 (with cardiac autonomic neuropathy) was in 97(53%) among diabetic patients. Among diabetic patients cardiac autonomic neuropathy (CAN) was 53%.

Serum Lipid Profile in Ischemic Heart Disease: A Cross-Sectional Analytical Study.

Risk of coronary heart disease and other forms of atherosclerotic vascular diseases, rises with plasma cholesterol concentration and in particular with the rise of ratio of total cholesterol to high density lipoprotein (HDL-C) cholesterol. A much weaker correlation also exists with plasma triglyceride concentration. Extensive large-scale randomized trials have shown that lowering total cholesterol and LDL-C concentrations reduces the risk of cardiovascular events including death, myocardial infarction and stroke and reduces the need for revascularisation.This cross-sectional analytical study was designed to observe association between lipid profile level with chronic ischaemic heart disease and the study was conducted in the Department of Biochemistry, Dhaka Medical College, Dhaka from July 2010 to June 2011. A total of 50 cases were selected purposively according to the selection criteria from the patients admitted in the Department of Cardiology, Dhaka Medical College Hospital with chronic ischaemic heart disease (IHD). Diagnosed IHD patients were taken as cases and 50 age- & sex- matched healthy subjects were taken as controls. Serum TC, TG, LDL-C & HDL-C were measured in all study subjects.The mean±SD of serum TC, TG, HDL-C and LDL-C concentration in cases were 314.54±73.72 mg/dl, 288.04±60.45 mg/dl, 36.02±4.12 mg/dl, and 178.62±22.7 mg/dl respectively and in controls were 174.64±18.97 mg/dl, 119.42±12.47 mg/dl, 43.04±2.58 mg/dl & 126.28±11.45 mg/dl respectively. Serum Total Cholesterol, TG & LDL-C were found to be significantly higher in cases than that of controls. Serum HDL-C was found to be significantly lower in cases than that of controls. The present study reveals that the patients with chronic ischemic heart disease is accociated with significantly higher levels of serum TC, TG and LDL-C whereas HDL-C was found to be lower in IHD patients.

Small Dense Low-density Lipoprotein and Cardiovascular Disease

Cardiovascular disease (CVD) is the leading cause of death worldwide and small dense low-density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular disease (CVD). We reviewed published studies on formation and measurement of sdLDL, as well as relationship between LDL subfractions and CVD. sdLDL particle formation is highly dependent on triglycerides (TG) levels, and the physicochemical properties of sdLDL particles provide a potential for increased atherogenicity. Various conditions (e.g. hypertriglyceridemia, diabetes mellitus, metabolic syndrome, chronic renal failure and HIV infections) with increased cardiometabolic risk are associated with increased sdLDLs. Most studies suggest that sdLDL particles are associated with increased prevalence of clinical and subclinical CVDs, as well as non-coronary forms of atherosclerosis. Moreover, LDL size seems to be an important determinant of the progression of CVD. Therapeutic modulation (mostly fibrates, but also some statins, as well as niacin and thiazolidinediones) of small LDL size, number and distribution may decrease CVD risk. However, no definitive causal relationship is yet established, probably due to the close association between sdLDL and triglycerides and other risk factors.

Biomarcadores de peroxidação lipídica na aterosclerose / Lipid peroxidation biomarkers in atherosclerosis

A aterosclerose é caracterizada por uma resposta inflamatória crônica da parede arterial, iniciada por uma lesão do endotélio, cuja etiologia está relacionada à modificação oxidativa da lipoproteína de baixa densidade. O objetivo deste trabalho é apresentar os principais metabólitos envolvidos nos processos bioquímicos de peroxidação lipídica, discutindo as vantagens e desvantagens dos métodos empregados para a mensuração dos biomarcadores de peroxidação lipídica relacionados com a aterosclerose. A avaliação da oxidação das lipoproteínas pode ser realizada pela determinação dos produtos gerados durante a peroxidação lipídica, como os isoprostanos, hidroperóxidos lipídicos, aldeídos, fosfolípides oxidados e os produtos da oxidação do colesterol. A suscetibilidade das partículas de lipoproteína de baixa densidade à oxidação pode ser avaliada in vitro, após a indução da peroxidação lipídica por azoiniciadores radicalares lipossolúveis, hidrossolúveis, ou mais comumente, pelos íons cobre. Por outro lado, as modificações da lipoproteína de baixa densidade, pela ação das lipoxigenases e peroxidases, ou oxidação não-enzimática, resultam no aumento da carga negativa destas partículas e podem contribuir para a geração in vivo de uma subfração de lipoproteína de baixa densidade minimamente oxidada, denominada lipoproteína de baixa densidade eletronegativa (lipoproteína de baixa densidade). A determinação das concentrações desta partícula pode ser realizada em plasma por cromatografia líquida ou por imunoensaios..Diversos métodos podem ser utilizados para a avaliação dos biomarcadores de peroxidação lipídica in vivo e in vitro, porém, a definição do marcador mais adequado, depende de uma avaliação criteriosa das vantagens, desvantagens e particularidades de cada análise, levando-se em consideração os objetivos do estudo que será conduzido.

Atherosclerosis is characterized by a chronic inflammatory response in the arterial wall triggered by endothelial injury. Its etiology is associated with the oxidative modification of low density lipoprotein. The objective of this work is to present the main metabolites involved in the biochemical process of lipid peroxidation and discuss the advantages and disadvantages of the methods used to measure the lipid peroxidation biomarkers associated with atherosclerosis. Lipoprotein oxidation can be assessed by determining the products generated during lipid peroxidation, such as isoprostanes, lipid hydroperoxides, aldehydes, oxidized phospholipids and products of cholesterol oxidation. The susceptibility of low density lipoprotein particles to oxidation can be assessed in vitro after induction of lipid peroxidation by oil-soluble or water-soluble azo initiators or more commonly by copper ions. On the other hand, low density lipoprotein modification by lipoxygenases and peroxidases or non-enzymatic oxidation increases the negative charge of these particles and may contribute to in vivo generation of a minimally oxidized low density lipoprotein subfraction called electronegative low density lipoprotein (low density lipoprotein). Plasma concentrations of these particles can be determined by liquid chromatography or immunoassays. Many methods can be used to assess lipid peroxidation biomarkers in vivo and in vitro, however determination of the most suitable biomarker depends on a minute assessment of the advantages, disadvantages and particularities of each analysis, bearing in mind the objectives of the study that will be performed.

In vitro model of atherosclerosis using coculture of arterial wall cells and macrophage

In order to determine the precise mechanism of the interactions between different types of cells, which are common phenomena in tissues and organs, the importance of coculture techniques are becoming increasingly important. In the area of cardiology, artificial arteries have been developed, based on the understanding of physiological communication of the arterial smooth muscle cells (SMC), endothelial cells (EC), and the extracellular matrix (ECM). In the study of atherosclerosis, the modification of low-density lipoprotein (LDL), which result in the recruitment and accumulation of white blood cells, especially, monocytes/macrophages, and foam cell formation, are hypothesized. Although there are well known animal models, an in vitro model of atherogenesis with a precisely known atherogenesis mechanism has not yet been developed. In this paper, an arterial wall reconstruction model using rabbit primary cultivated aortic SMCs and ECs, was shown. In addition, human peripheral monocytes were used and the transmigration of monocytes was observed by scanning electron and laser confocal microscopy. Monocyte differentiation into macrophages was shown by immunohistochemistry and comprehensive gene expression analysis. With the modified form of LDL, the macrophages were observed to accumulate lipids with a foamy appearance and differentiate into the foam cells in the ECM between the ECs and SMCs in the area of our coculture model.

Effect of human scavenger receptor SR-A Ⅰ overexpression on uptaking ox-LDL and adhesion in 293T cells / 中国病理生理杂志

AIM:To construct the recombinant eukaryotic expression plasmid pEGFP-C1-SR-A I for the high expression in 293T cells in order to identify functions of savenger receptor-A I(SR-A).METHODS:The primer was designed according to MSR1 cDNA and pEGFP-C1-SR-A I was constructed by standard molecular cloning technique and enzyme digestion.After sequencing,the plasmid was transfected into 293T cells by lipidosome method.The expression of scavenger receptor-A I was identified by RT-PCR and Western blotting.The foam cells were evaluated by the formation of lipid granules in the cells with oil red staining.Cell adhesion was analyzed by cell adhesion assay.RESULTS:24 h after transfection,SR-A I mRNA was highly expressed and the high level of the protein was detected.The ratio of foam cell formation was doubled,the efficacy of cell adhesion was enhanced two times compared to the control group and the empty vector group.CONCLUSION:The recombinant eukaryotic expression plasmid has been constructed successfully with enhancing the function of uptake ox-LDL and adhesion in 293T cells by overexpression of SR-A I.

The Effect of LDL Oxidation Caused an Atherosclerosis in Macrophage Cells * : The Antioxidant Effect of Ganhaungenin / 대한면역학회지

Oxidatively modified low density lipoprotein (LDL) could contribute to one of the atherosclerotic processes through its uptake by the scavenger receptor of macrophage. The aim of the present study was to examine whether ganghaungenin has an antioxidant effect. For the approach of the aim, a lipid peroxidation of LDL, the changes of degradation and negative charge of LDL, and LDL uptake in macrophage were measured after ganghaungenin was treated in the reaction process of LDL oxidation. The effective LDL oxidation was performed with treatment of 20 pM CuSO4 for 5 hours. Quercetin, one of the well-known antioxidant, was used as a positive control. The antioxdant effect of ganghaungenin on the LDL oxidation were examined at concentrations of both 40 p,M and 80 p,M for Sh. Ganghaungenin significantly inhibited the lipid peroxidation of LDL. It inhibited the oxidation-enhanced degradation and negative charge of LDL. Even 100 p,M of it did not have any toxic effects on macrophage. It inhibited the uptake of the oxidized LDL into macrophage. These data revealed that ganghaungenin obtained from Scutellaria Baicalensis Georgi was a potent antioxidant in inhibiting the oxidative modification of LDL. Conclusively, these findings indicate that ganghaungenin in physiologic concentrations could inhibit the oxidative modification of LDL in vivo, and suggest that ganghaungenin could be also used for the atherosclerosis prevention.

Effect of adrenomedullin on tissue factors and TFPI expression in HUVECs treated with oxLDL / 中国病理生理杂志

AIM: To explore the role of adrenomedullin (AM) in tissue factor (TF) and TFPI expression in HUVECs stimulated with oxLDL and to investigate its possible signal transduction pathway. METHODS: Using chromogenic assay and RT-PCR technique, TF and TFPI protein activity and mRNA level in cultured HUVECs were observed. The signal transduction pathway of AM action was further analyzed by applying Rp-cAMP (cAMP antagonist), PD098059 (MAPK inhibitor) and H7 (PKC inhibitor). RESULTS: AM inhibited TF protein activity and mRNA expression in HUVECs treated with oxLDL in a concentration-dependent fashion; AM alone increased TFPI protein activity and mRNA expression in concentration-dependent and time-dependent manner. Moreover, AM reversed the decrease in TFPI protein activity and mRNA level caused by oxLDL; AM-induced TFPI expression was inhibited by cAMP and MAPK inhibitors. CONCLUSION: AM can reverse the effects of oxLDL on TF and TFPI expression in HUVECs, which can help improve the state of blood coagulation in atherosclerosis and delay development of atherosclerosis.

EFFECT OF MAGNESIUM SUPPLEMENTATIO N ON OXIDATIVE MODIFICATION OF HUMAN LOW DENS ITY LIPOPROTEIN / 营养学报

Objective: The effects of magnesium on the oxidation of low density lipoprotein (LDL) were systematically investigated by two different oxidation systems. Methods: LDLs were isolated from pooled healthy human fresh sera by ultracentrifugation. Oxidation of LDL was induced by adding Cu 2+ or co-cultured with cultured human umbilical vein endothelial cells. Conjugate diene was measured to assess the susceptibility of LDL to oxidation. The extent of LDL modification was determined by measuring the formation of thiobarbituric acid reaction substances (TBARS). Results: (1)The presence of Mg 2+ resulted in a protracted lag phase at doses of 0.3 mmol/L, 0.6 mmol/L, 1.2 mmol/L, and 2.4 mmol/L, as well as decreased production of TBARS when LDL was oxidized by the addition of Cu 2+ , at doses of 0.3 mmol/L and 0.6 mmol/L Mg 2+ .(2)Treatment of LDL with Mg 2+ (0.3 mmol/L, 0.6 mmol/L, 1.2 mmol/L, and 2.4 mmol/L) reduced the production of TBARS during endothelial cell-mediated LDL oxidation, P