Normal HDL Research Articles

Metabolic and inflammatory links to rotator cuff tear in hand osteoarthritis: A cross sectional study.

ObjectivesTo estimate the prevalence and associated factors of rotator cuff tear (RCT) in patients with hand osteoarthritis (HOA).MethodsBetween June 2013 and December 2015, we recruited 1150 participants in rural area of South Korea. Of the 1150 participants, 307 participants with HOA were analyzed. Plain radiography of both hands, magnetic resonance imaging of both shoulders, and serum levels of high-sensitive C-reactive protein (hsCRP) and high-density lipoprotein (HDL) were obtained for all patients. HOA and RCT were diagnosed by clinical and radiologic findings.ResultsThe prevalence of RCT in patients with HOA (192/307, 62.5%) was higher than that in those without HOA (410/827, 49.5%, p<0.001). Among the 307 patients with HOA, the patients with RCT were older, and had higher hsCRP and lower HDL levels than the patients without RCT. Multiple logistic regression analysis confirmed significant associations of age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.02–1.11), serum hsCRP levels ≥0.6mg/L (OR, 1.68; CI, 1.00–2.80), and low HDL levels (male, <50 mg/dL; female, <40 mg/dL) (OR, 1.93; CI, 1.05–3.56) with RCT in patients with HOA. For patients below 60 years old, the prevalence of RCT was 2.8-fold higher in the low HDL group than normal HDL group (p = 0.048). Finally, the prevalence of RCT was 2.6-fold higher in patients with HOA with both elevated hsCRP and low HDL levels compared with those with neither (p<0.05).ConclusionsOur findings suggest inflammation and metabolic factors were associated with the prevalence of RCT in HOA patients.

System simulations for the ALICE ITS detector upgrade

The ALICE experiment at the CERN LHC will feature several upgrades for Run 3, one of which is a new Inner Tracking System (ITS). The ITS upgrade is currently under development and commissioning, and will be installed during the ongoing long shutdown 2. A number of factors will have an impact on the performance and readout efficiency of the ITS in run 3, and to that end, a simulation model of the readout logic in the ALPIDE pixel sensor chips for the ITS was developed, using the SystemC library for system level modeling in C++. This simulation model is three orders of magnitude faster than a normal HDL simulation of the chip and facilitates simulations of an increased number of events for a large portion of the detector. In this paper, we present simulation results, where we have been able to quantify detector performance under different running conditions. The results are used for system configuration as well as for the ongoing development of the readout electronics.

Does the nutritional status of acute stroke patients affect the neurological status in the early post-stroke period?

ABSTRACTAccording to recent reports, malnutrition may be associated with a worse prognosis in stroke patients. The aim of this study was to determine the nutritional status of stroke patients and its impact on neurological and functional status of patients in the early post-stroke period. Our prospective study included a total of 128 patients admitted to the Stroke Unit. The assessment was made in the patients within the first week after the onset of stroke symptoms. Groups of patients with abnormal body mass index (BMI <20kg/m2 or >25kg/m2) were compared to the group of normal BMI, serum albumin, total cholesterol, HDL and LDL levels were determined in each patient within 24h following admission. The analysis showed that the patients with lower levels of serum albumin and triglycerides had higher scores in the National Institutes of Health Stroke Scale (NIHSS) on admission. Patients with a higher risk of malnutrition, confirmed by the Subjective Global Assessment scale, had higher NIHSS scores. The study showed a positive relationship between the nutritional status and worse neurological status of patients in the early post-stroke period.Abbreviation: NIHSS; Rankin scale

Modulation of cholesterol efflux capacity in patients with myocardial infarction

Epidemiologic studies consistently demonstrated that patients with coronary artery disease (CAD) and low HDL cholesterol (HDL-C) are more likely to develop major adverse cardiovascular events as compared with those with normal or high HDL. However, several large randomized trials failed to demonstrate that a substantial, pharmacological-based, increase of HDL-C concentrations results in a clinically significant reduction of ischemic outcomes. This has been largely attributed to the fact that, although these drugs are able to raise the HDL-C concentration, they have no effect on HDL-C atheroprotective function. Subsequently, the 'HDL hypothesis' evolved, and the focus shifted from raising the concentration of HDL-C to raising the reverse cholesterol transport (RCT) function by increasing patients cholesterol efflux capacity (CEC) instead. Indeed, new data suggest that HDL-C metabolism and the ability of the HDL molecule to transport cholesterol from the atherosclerotic plaque to the liver, measured by the CEC, is more important than steady-state HDL-C levels. Modulation of the CEC has become, therefore, a promising therapeutic target in CAD patients. This article reviews the current data on the 'cholesterol efflux hypothesis' and discuss its ability to be modulated has a potential therapeutic target. Recent data have demonstrated that impaired serum CEC was associated with increased mortality after a myocardial infarction (MI). Thus, therapeutic intervention aiming to improve CEC and RCT may reduce the risk of recurrent events. Early phase clinical studies targeting CEC showed promising results and a megatrial is ongoing testing the hypothesis that an improved RCT trough a modulation of the CEC can modify patient's prognosis after an acute MI. The 'cholesterol efflux hypothesis' is now supported by several clinical studies and is being tested with a therapeutic candidate in a megatrial enrolling high-risk patient with MI.

Efficacy of a Validated Yoga Protocol on Dyslipidemia in Diabetes Patients: NMB-2017 India Trial.

Background: Dyslipidemia is considered a risk factor in Type 2 diabetes mellitus (T2DM) resulting in cardio-vascular complications. Yoga practices have shown promising results in alleviating Type 2 Diabetes pathology. Method: In this stratified trial on a Yoga based lifestyle program in cases with Type 2 diabetes, in the rural and urban population from all zones of India, a total of 17,012 adults (>20 years) of both genders were screened for lipid profile and sugar levels. Those who satisfied the selection criteria were taught the Diabetes Yoga Protocol (DYP) for three months and the data were analyzed. Results: Among those with Diabetes, 29.1% had elevated total cholesterol (TC > 200 mg/dL) levels that were higher in urban (69%) than rural (31%) Diabetes patients. There was a positive correlation (p = 0.048) between HbA1c and total cholesterol levels. DYP intervention helped in reducing TC from 232.34 ± 31.48 mg/dL to 189.38 ± 40.23 mg/dL with significant pre post difference (p < 0.001). Conversion rate from high TC (>200 mg/dL) to normal TC (<200 mg/dL) was observed in 60.3% of cases with Type 2 Diabetes Mellitus (T2DM); from high LDL (>130 mg/dL) to normal LDL (<130 mg/dL) in 73.7%; from high triglyceride (>200 mg/dL) to normal triglyceride level (<200 mg/dL) in 63%; from low HDL (<45 mg/dL) to normal HDL (>45 mg/dL) in 43.7% of T2DM patients after three months of DYP. Conclusions: A Yoga lifestyle program designed specifically to manage Diabetes helps in reducing the co-morbidity of dyslipidemia in cases of patients with T2DM.

76 GENETIC ARCHITECTURE OF PERSISTENT ATTENTION DEFICIT/HYPERACTIVITY DISORDER

High-density lipoprotein (HDL) plays a key role in protecting against atherosclerosis. In cardiovascular disease, HDL can be nitrated and chlorinated by myeloperoxidase (MPO). In this study, we discovered that MPO-oxidized HDL is dysfunctional in promoting endothelial repair compared to normal HDL. Proliferation assay, wound healing, and transwell migration experiments showed that MPO-oxidized HDL was associated with a reduced stimulation of endothelial cell (EC) proliferation and migration. In addition, we found that Akt and ERK1/2 phosphorylation in ECs was significantly lower when ECs were incubated with oxidized HDL compared with normal HDL. To further determine whether oxidized HDL diminished EC migration through the PI3K/Akt and MEK/ERK pathways, we performed experiments with inhibitors of both these pathways. The transwell experiments performed in the presence of these inhibitors showed that the migration capacity was reduced and the differences observed between normal HDL and oxidized HDL were diminished. Furthermore, to study the effects of oxidized HDL on endothelial cells in vivo, we performed a carotid artery electric injury model on nude mice injected with either normal or oxidized HDL. Oxidized HDL inhibited reendothelialization compared to normal HDL in vivo. These findings implicate a key role for MPO-oxidized HDL in the pathogenesis of cardiovascular disease.

Biological Factors Related to Distress of Patients with Diabetes Type-2

Objective: The purpose of this study was to analyze the relationship between biological factors with distress of diabetes type 2.Material and Methods: The research method is quantitative correlation. Samples were taken by accidental sampling method for 3 months (November 2017-January 2018) in 44 patients who were treated at PKU Muhammadiyah Yogyakarta Hospital and PKU Muhammadiyah Bantul Hospital in Yogyakarta, Indonesia. The instruments of the study were medical records, diabetes distress scale (DDS17) questionnaire, sphygmomanometer, scales, and microtoise. Data analysis used was ordinal logistic regression.Result and Discussion: The results of the study showed 70.5% respondents were hyperglycemic; 79.5% respondents had normal total cholesterol; 45.5% respondents had normal HDL cholesterol; 52.3% respondents had normal LDL cholesterol; 63.6% respondents had normal triglycerides; 68.2% respondents had a normal BMI; 63.6% respondents had comorbidities; 50.0% respondents had complications; 72.7% respondents suffer from hypertension; and 68.2% respondents suffer from DM&gt; 5 years. The result also showed 50.0% respondents had mild distress; 43.2% respondents had moderate distress; and 6.8% had severe distress.Conclusion: It was concluded that biological factors related to distress were comorbidities, complications, BMI and total cholesterol.International Journal of Human and Health Sciences Vol. 03 No. 04 October’19 Page : 207-217

Lipoprotein modulation of proteinuric renal injury

High-density lipoprotein (HDL) and its main protein, apolipoprotein AI (apoAI), have established benefits in various cells, but whether these cytoprotective effects of HDL pertain to renal cells is unclear. We investigated the in vitro consequences of exposing damaged podocytes to normal apoAI, HDL, and apoAI mimetic (L-4F), and the in vivo effects of L-4F on kidney and atherosclerotic injury in a podocyte-specific injury model of proteinuria. In vitro, primary mouse podocytes were injured by puromycin aminonucleoside (PAN). Cellular viability, migration, production of reactive oxygen species (ROS), apoptosis, and the underlying signaling pathway were assessed. In vivo, we used a proteinuric model, Nphs1-hCD25 transgenic (NEP25+) mice, which express human CD25 on podocytes. Podocyte injury was induced by using immunotoxin (LMB2) and generated a proteinuric atherosclerosis model, NEP25+:apoE−/− mice, was generated by mating apoE-deficient (apoE−/−) mice with NEP25+ mice. Animals received L-4F or control vehicle. Renal function, podocyte injury, and atherosclerosis were assessed. PAN reduced podocyte viability, migration, and increased ROS production, all significantly lessened by apoAI, HDL, and L-4F. L-4F attenuated podocyte apoptosis and diminished PAN-induced inactivation of Janus family protein kinase-2/signal transducers and activators of transcription 3. In NEP25+ mice, L-4F significantly lessened overall proteinuria, and preserved podocyte expression of synaptopodin and cell density. Proteinuric NEP25+:apoE−/− mice had more atherosclerosis than non-proteinuric apoE−/− mice, and these lesions were significantly decreased by L-4F. Normal human apoAI, HDL, and apoAI mimetic protect against podocyte damage. ApoAI mimetic provides in vivo beneficial effects on podocytes that culminate in reduced albuminuria and atherosclerosis. The results suggest supplemental apoAI/apoAI mimetic may be a novel candidate to lessen podocyte damage and its complications.

High blood pressure in a type 2 diabetic population of the city of Sidi Bel Abbes, Algeria

The association of type 2 diabetes and high blood pressure (HT) results in increased cardiovascular risk and accelerated degenerative complications of diabetes. We aimed to determine the frequency of HT in type 2 diabetic patients and to evaluate the relationship between this association with the micro-angiopathy complications. A cross sectional study was conducted in 279 type 2diabetic patients (67.7% women, 32.3% men), mean age: 60.16 ± 0.60 years old, diabetes duration: 11 ± 0.47 years, body mass index: 28.70 kg/m 2 ; 47.9% of patients were overweight and 32.3% were obese. HT was found in 58.9% of patients (62.7% women, 50.6% men). This percentage significantly increased with age ( P < 0.001): 20% of patients younger than 40 years old, 40% aged 40–50 years, 47% aged 50–60 years and 74% over 60 years old. HT also significantly increased with duration of diabetes ( P = 0.001): 40% of patients whose duration of diabetes did not exceed 5 years, 55% between 5 and 10 years, 67% between 10 and 20 years, and 74% among those whose duration of diabetes exceeded 20 years. HT occurred in 60% of patients with normal weight, in 55% of overweight patients and in 62% of obese patients without significant difference. HT was found in 59% of patients with normal HDL plasma levels versus 50% of patients with low HDL levels, in 58% with a normal triglyceride vs. 56% in those with high levels of TG. For degenerative complications, retinopathy was found in 34% of patients (36.6% men, 29% women) without significant difference between sexes. Nephropathy was found in 9% of patients, all those were women. Using unvaried analysis, these complications were significantly correlated with HT with P = 0, 013 and 0,011 respectively. Retinopathy was found in 40% of hypertensive diabetics vs. 24% in normotensive diabetics. Nephropathy was found in 13% of hypertensive diabetics vs. 3% in normotensive diabetics. Our study confirms the association between diabetes and HT. We observed a high prevalence of HT in our diabetic population increasing with age and duration of diabetes. High risk of degenerative complications requires intensive management of HT in diabetic patients.

Effect of the components of the metabolic syndrome on pulmonary function. The unexpected role of high-density lipoprotein cholesterol

Metabolic syndrome is a condition that predisposes to cardiovascular disease and diabetes mellitus. In addition, it can have effects over neoplastic pathologies, liver and pulmonary function. Our objective is to analyze the effect of the metabolic syndrome and its components on pulmonary function. 110 subjects from Mexico City were evaluated and anthropometric measurements, glucose determination, triglycerides and high-density lipoprotein (HDL) cholesterol were made. They underwent a simple spirometry. Diagnosis of metabolic syndrome was made following the NCEP-ATPIII criteria. Of 110 individuals, 90 (82%) were women and 20 men (18%); 71 subjects (65%) presented metabolic syndrome. Subjects with central obesity had a forced vital capacity (FVC) lower than subjects without central obesity (2.72 vs. 3.11 liters; p < 0.05). Those with low HDL had better spirometric results than subjects with normal HDL (FEV1 2.36 vs. 1.85 liters; p < 0.05), FVC (2.95 vs. 2.45 liters; p < 0.05) and FEV1/FVC ratio (0.78 vs.74; p < 0.05). Hypertensive subjects presented lower volumes in FEV1 (1.91 vs. 2.38; p < 0.05) and FVC (2.49 vs. 2.99; p < 0.05). There is no difference between the spirometry volumes of patients with metabolic syndrome versus the metabolically healthy subjects. The only factors associated with a decrease in FEV1 and FVC are central obesity and arterial hypertension. An unexpected finding was the negative correlation between HDL levels and lung function.

Effects of Poly-herbal Tablet as Herbal Medicine on Lipid Level

Dyslipidemia is one of the high-risk factors that cause cardiovascular disease and the prevalence is increasing all the time. Garlic (Alii sativi) has been suggested to reduce serum lipid level. Poly-herbal is herbal medicine that has been widely used in Indonesia, and it contains Alii sativi, Belericae fructus, Curcumae aeroginosae, and Amomi fructus extract. This study aimed to evaluate the effects of poly-herbal tablet on lipid levels in dylipidemia subjects. The study was conducted for 6 weeks on 58 dyslipidemic subjects. The subject was divided into 2 groups. Group 1 was given Poly-herbal with the dose 2x1200 mg, and group 2 was not given anti-dyslipidemic drugs (control group). Serum lipid level (total cholesterol, LDL, HDL, and triglycerides) were checked before the treatment (H0) and after the treatment (M6). There was a significant difference on the reduction of serum lipids level between the group that given Poly-herbal vs control group, respectively total cholesterol (-12.04±3.2 vs 8.38±4.3; p=.000), LDL (-4.42±2.8 vs 6.93±4.7; p=.049) and HDL (-2.62+1.0 vs 3.31+1.4; p=.005). Triglyceride level on Poly-herbal group is not significantly decreased. In Poly-herbal group there was also a decrease in HDL levels which was not statistically significant (-2.62±1, p=.015). This is probably due to the HDL baseline in the control group included in the normal HDL category (57.38 ± 14.9) so that the HDL levels after being given treatment did not increase. This study suggests that using Poly-herbal in dyslipidemia subjects can reduce the level of total cholesterol and LDL.

Yerba Mate (Ilex paraguariensis) and Dimethyl Fumarate Can Improve Metabolic Syndrome Condition Induced by High Fat Diet in Mice

IntroductionMetabolic syndrome (MS) is a combination of clinical signs and symptoms that occur together and directly contribute to the risk of developing cardiovascular disease and diabetes. Some studies suggest that the prevalence of MS in the US is 32% of the population, while in Brazil this level reaches 23%. The criteria for the classification of MS are diverse, but according to the WHO, the presence of diabetes or reduced glucose tolerance or insulin resistance, associated with at least two of the following conditions: elevation of blood pressure, dyslipidemia and obesity are considered. MS confers a two‐fold increased risk for developing cardiovascular disease, two to four times the risk of stroke, three to four times the risk of acute myocardial infarction. Our hypothesis is that toasted yerba mate and dimethyl fumarate have a therapeutic effect on the metabolic syndrome in mice.MethodsMetabolic syndrome was induced by hyperlipidic diet (60% of total calorie) in C57BL / 6 mice for 12 weeks, and treatment was performed concomitantly with yerba mate (2 mg / g) and dimethyl fumarate (0.24 mg / g) diluted in water, to which the animals had free access. The groups were separated as follows: control group (standard diet and water), HFD group (hyperlipidic diet and water), HFD + Mate group (hyperlipidic diet and mat herb tea) and HFD + DMF group (hyperlipidic diet and dimethyl fumarate).ResultsIt was observed that the HFD + Mate group obtained an increase in body mass in the same way as the HFD group, also increasing triglyceride levels, but maintained normal HDL levels. The HFD + DMF group, however, remained with body mass equal to the control group, maintaining normal levels of HDL and triglycerides. Both the HFD + Mate group and the HFD + DMF group remained at optimal glycemic levels, including glucose tolerance and insulin resistance tests. Histological analysis of the liver showed hepatic steatosis in the HFD group, but not in the HFD + Mate and HFD + DMF groups.ConclusionDMF was effective to prevent metabolic syndrome, once the hallmarks glucose, body weight, triglycerides and HDL cholesterol were kept similar to control group. DMF also protected against hepatic steatosis. About mate tea, the effect was more modest than DMF, once only HDL cholesterol and glucose were protected, as well as hepatic steatosis was avoided. These data suggest DMF can modulate satiation preventing the syndrome metabolic development.Support or Funding InformationBrazilian Research Agencies ‐ CAPES, CNPq and FAPERJThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Correlation between HDL Level with Clinical and Biochemical Markers of Atherogenesis

Introduction: HDL cholesterol (HDL-C) level is an independent predictor of risk for cardiovascular events in both genders, low levels of which have been demonstrated to have an inverse association with cardiovascular disease and mortality. Anthropometric measurements serve as surrogate markers for atherogenic burden. Atherosclerosis represents a chronic inflammatory process and low HDL being an inflammatory state, inflammatory markers such as high-sensitivity C Reactive Protein (hs-CRP) may provide an adjunctive method for global assessment of cardiovascular risk. TG/HDL ratio has been proved to have a high association with prevalence of metabolic syndrome and with insulin resistance.Aim: To find out the correlation between High Density Lipoprotein (HDL) level with clinical and biochemical markers of atherogenesis.Materials and Methods: This cross-sectional study was conducted with a study population of 200 individuals, who were either in-patients or outpatients in the Department of Medicine at Kasturba Medical College (KMC), Manipal Karnataka, India. (Study period July 2012-July 2014). Individuals aged 18-70 years being investigated for dyslipidemia for the first time were included. Data was collected by in person interview by specific questionnaire. Height, weight, waist circumference and hip circumference were measured as per standard protocol. Laboratory reports were noted for the estimation of Fasting Blood Sugar (FBS), HDL and Triglycerides (TG), hs-CRP, fasting insulin. Serum LDL was calculated. Statistical data analysis was done using SPSS 16.0 version. Mean and median values were calculated corresponding to the data. Results were analysed using Pearson’s and Spearman’s correlation coefficient. Independent t- est and Mann-Whitney’s tests were used for calculation of significance of correlation.Results: Among the studied individuals 53% (106) were males and 47% (94) were females. A total of 77%(154) of the individuals with low HDL and 70%(140) individuals with normal HDL had abnormal waist circumference. Mean Waist Hip Ratio (WHR) was same across groups with low and normal HDL. Mean Body Mass Index (BMI) was similar in both the groups among males; however, a statistically significant difference was found among females. Abnormal waist circumference was found similar across both the groups. Median hs-CRP showed a statistically significant higher values among individuals with lower HDL. Fasting insulin and HOMA-IR was higher among individuals with low HDL (vs normal HDL), but it was statistically insignificant. Median TG/HDL ratio among 41 individuals were found to be 3.08, which was higher than the cut-off to signify insulin resistance. HOMA-IR and TG/HDL ratio showed a statistically significant positive correlation suggesting that TG/HDL ratio can be used as a marker of insulin resistance.Conclusion: This study revealed that anthropometric indices showed an inverse correlation with HDL levels, with BMI being a better predictor of HDL-C changes. HDL was lower in individuals with insulin resistance, with TG/HDL ratio being a significant marker of insulin resistance.

A CONTRIBUTION OF RARE COPY NUMBER VARIATIONS TO THE DEVELOPMENT OF ATTENTION DEFICIT HYPERACTIVITY DISORDER: GENOME-WIDE META-ANALYSES IN 12548 INDIVIDUALS

High-density lipoprotein (HDL) plays a key role in protecting against atherosclerosis. In cardiovascular disease, HDL can be nitrated and chlorinated by myeloperoxidase (MPO). In this study, we discovered that MPO-oxidized HDL is dysfunctional in promoting endothelial repair compared to normal HDL. Proliferation assay, wound healing, and transwell migration experiments showed that MPO-oxidized HDL was associated with a reduced stimulation of endothelial cell (EC) proliferation and migration. In addition, we found that Akt and ERK1/2 phosphorylation in ECs was significantly lower when ECs were incubated with oxidized HDL compared with normal HDL. To further determine whether oxidized HDL diminished EC migration through the PI3K/Akt and MEK/ERK pathways, we performed experiments with inhibitors of both these pathways. The transwell experiments performed in the presence of these inhibitors showed that the migration capacity was reduced and the differences observed between normal HDL and oxidized HDL were diminished. Furthermore, to study the effects of oxidized HDL on endothelial cells in vivo, we performed a carotid artery electric injury model on nude mice injected with either normal or oxidized HDL. Oxidized HDL inhibited reendothelialization compared to normal HDL in vivo. These findings implicate a key role for MPO-oxidized HDL in the pathogenesis of cardiovascular disease.

Metabolic Syndrome Knowledge among Adults with Cardiometabolic Risk Factors: A Cross-Sectional Study.

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors. Many people may be unaware of their risk for MetS. A cross-sectional, descriptive study was conducted among hospitalized patients with at least one cardiometabolic risk factor in Mainland China. This study assessed the MetS knowledgelevel(through MetS Knowledge Scale, MSKS) and examined the potential predictors by regression analysis. A total of 204 patients aged 58.5 ± 10.1 years (55% males) participated in this study. The majority of participants had no history of hypertension (54%), dyslipidemia (79%), or diabetes (85%). However, 56% of these participants had at least three cardiometabolic risk factors, indicating the presence of MetS. The average MSKS was very low (mean = 36.7 ± 18.8, possible range = 0–100), indicating the urgent needs of MetS education in current practice. Predictors of better MetS knowledge included higher educational level, history of dyslipidemia, and normal high-density lipoprotein cholesterol (F (8, 195) = 9.39, adjusted R2 = 0.192, p < 0.001). In conclusion, adults with cardiometabolic risk factors are at risk of developing MetS, but with a low level of knowledge. Specific health education on MetS should be provided, particularly for those with limited formal education or inadequate lipid management.

Higher Triglyceride and Normal HDL-C Concentrations, the Triglyceride/HDL-C Concentration Ratios ≥ 3.5, and Insulin Resistance as Potential Predictors of Developing Higher Paroxetine Concentrations and Suicide in the Early Months of Medication

Background: There are several reported results. Hazard ratios for suicide tended to increase with dose for selective serotonin reuptake inhibitors (SSRIs). The suicide rate in the first three months following initiation of paroxetine exposure was 799 per 100,000 person-years, while, annual suicide rates for depression and anxiety were 81.8 and 76.7, respectively. SSRIs serum concentrations were significantly associated with increases of triglyceride (TG) levels. SSRIs inhibited insulin signaling and beta cell function by a dose-dependent manner.Objective: Based on symptoms and blood lipid levels indicated by a young patient who committed suicide, my objective is to propose that higher TG concentrations above the normal range, normal high-density lipoprotein cholesterol (HDL-C) concentrations, and the TG/HDL-C concentration (mg/dL) ratios ≥ 3.5 to estimate insulin resistance are potentially useful in identifying individuals who are developing higher paroxetine concentrations.Methods: The glucose and lipid levels in the blood examination which was performed in an emergency hospital to where the patient was delivered by ambulance after his abnormal behaviors on the 14th day after the start of paroxetine treatment, were used for calculation and examination. Fasting TG levels were estimated by calculating TG values (TG-Cal) using the measured value of TG and a formula reported by Hitze et al., or the measured values of total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C), and nine formulas referred and reported by Dansethakul et al. Paroxetine levels in the patient’s serum were estimated by calculation using the regression coefficient of TG 46.49 mg/dL, with which the paroxetine serum concentration 75 ng/mL was associated in the results reported by Fjukstad et al.   Results: The 20-year-old patient free of recent suicidal ideation developed intense violent suicidal preoccupation, and exhibited abnormal behaviors in the first 41 days after the start of paroxetine treatment 10 mg twice daily. He sent emails with advanced notice of suicide to his friend on the 7th, 17th, and 18th days, drank alcohol alone and exhibited abnormal behaviors in a market place around noon, blacked out, and was ambulanced to the emergency hospital on the 14th day. Finally, he carried out suicide on the 41st day after three days of abrupt discontinuation of paroxetine. He never exhibited these abnormal behaviors before paroxetine exposure. The levels of glucose, TG, TC, HDL-C, and LDL-C measured in the blood examination at 15:56 on the 14th day after the start of paroxetine treatment were 111, 498, 185, 53, and 92 mg/dL, respectively. The levels of TC, HDL-C, and LDL-C were in the normal ranges, respectively, probably suggesting metabolic normality of the patient before paroxetine exposure. In order to estimate the fasting TG level, TG-Cal values were calculated to be 278, 200, 258, 240, 268, 272, 310, 308, 311, and 250 mg/dL in the range of 200 – 311 mg/dL beyond the normal range of TG 50 – 150 mg/dL. TG-Cal/HDL-C ratios were also calculated to be in the range of 3.8 – 5.9 (200/53 – 311/53), probably suggesting that the patient was in the stage of insulin resistance development. The paroxetine level in the patient’s serum was estimated to be in the range of 161 – 387 ng/mL by calculation using formulas 75(TG-Cal – 71)/46.49, 75(TG-Cal – 92.25)/46.49, and 75(TG-Cal – 100)/46.49, on the assumption that the patient’s TG levels before paroxetine exposure were 71, 92.25, and 100 mg/dL, respectively. The paroxetine concentrations in the range of 161 – 387 ng/mL were much higher than the therapeutic reference range 30 – 120 ng/mL.    Conclusions: The above results probably suggest that paroxetine exposure, higher TG concentration, higher paroxetine concentration, and suicide coincided in the patient. Follow-up measurements of TG and HDL-C concentrations and the TG/HDL-C ratios have a potential to predict and prevent suicides in the early months of paroxetine exposure.Â

The Role of Circulating Regulatory T Cell Levels on Subclinical Atherosclerosis and Cardiovascular Risk Factors in Women with Systemic Lupus Erythematosus.

The increase in cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE) is not fully explained by traditional CVD risk factors. Regulatory T cells (Treg cells) are considered atheroprotective. We investigated the relationship between the absolute number of different phenotypes of Treg cells and abnormal carotid intima-media thickness (IMT) in women with SLE. Sixty-six women with SLE with no history of CV disease were included. Carotid IMT was quantified by ultrasound. Abnormal carotid IMT was defined as ≥0.8 mm and two groups were compared according to this definition. Flow cytometry was used to analyze Foxp3 and Helios expression in peripheral blood CD4 T cells. A significantly higher level of absolute CD4+CD25+FoxP3high T cells was present in patients with abnormal carotid IMT compared with those without (1.795 ± 4.182 cells/μl vs. 0.274 ± 0.784 cells/μl; p = 0.003). However, no correlations were found between any Treg cell phenotypes and carotid IMT. Only the absolute number of CD4+CD45RA+FoxP3low T cells was significantly decreased in SLE patients with low HDL cholesterol compared with those with normal HDL cholesterol (0.609 ± 2.362 cells/μl vs. 1.802 ± 4.647 cells/μl; p = 0.009 and 15.358 ± 11.608 cells/μl vs. 28.274 ± 34.139; p = 0.012, respectively). In conclusion, in SLE women, diminished levels of Treg cells based on flow cytometry were not a good indicator of abnormal carotid IMT.

Periodontitis and platelet count: A new potential link with cardiovascular and other systemic inflammatory diseases.

As an infection-driven inflammatory disease, periodontitis could lead to a reactive increase in platelet count. This mechanism could partially mediate the well-documented association between periodontitis and atherosclerotic cardiovascular disease. The aim of this cross-sectional study was to test the presence of an association between periodontitis and platelet count in a representative sample of the South Korea population. A total of 5,197 subjects representative of 34.9 million of adults were examined. Multivariate regression analyses were applied controlling for age, gender, smoking status, educational level, body mass index, alcoholism, diabetes and hypertension status, vitamin D serum levels and total cholesterol, triglycerides, HDL and LDL blood levels. Compared to the non-severe periodontitis group, subjects with severe periodontitis (CPI=4) displayed 13,048.93 more platelets for μl of blood (95% CI: 3,296.26-22,801.61, p=0.009) in the fully-adjusted model. The association between severe periodontitis and platelet count has shown to be highlighted in subjects aged more than 60years, females, non-smokers and with normal HDL blood levels. A systemic inflammatory biomarker (white blood cell count) explained the 19.25% of this association. Within the limitations of this study, periodontitis-especially severe-is independently associated with a considerable increase in platelet count which is explained, at least in part, by an increase in the systemic inflammation.

Apolipoprotein A5 gene variants are associated with decreased adiponectin levels and increased arterial stiffness in subjects with low high-density lipoprotein-cholesterol levels.

We performed a genome-wide association study to find genetic variants associated with high-density lipoprotein (HDL)-cholesterol levels in a Korean population and verified two apolipoprotein A5 (APOA5) gene variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), in 612 subjects with low HDL-cholesterol (cases) and 1536 subjects with normal HDL-cholesterol (controls). To explain this association, we compared clinical outcomes according to their genotype in normal (control) and low HDL (case) groups. In both the case and control groups, the rare alleles of rs662799 and rs2075291 were associated with higher triglyceride and lower HDL-cholesterol levels. In the subjects with the rs662799 CC genotype, lower levels of apoA-I and apoA-V and a smaller low-density lipoprotein (LDL) particle size were detected in both the case and control groups. In the case group, APOA5 rs662799 single nucleotide polymorphisms (SNPs) were associated with lower adiponectin and higher brachial-ankle pulse wave velocity (ba-PWV). Our results show that two APOA5 variants, rs662799 (-1131T>C) and rs2075291 (c.553G>T), are associated with HDL-cholesterol levels in a Korean population, and suggest that individuals with an APOA5 rs662799 CC genotype are at higher risk of atherosclerosis, particularly when they have low HDL-cholesterol, and this association is related to adiponectin levels.

High-Density Lipoprotein Particles, Cell-Cholesterol Efflux, and Coronary Heart Disease Risk.

Objective- The cell-cholesterol efflux capacity of HDL (high-density lipoprotein) is inversely associated with coronary heart disease risk. ABCA1 (ATP-binding cassette transporter A1) plays a crucial role in cholesterol efflux from macrophages to preβ-1-HDL. We tested the hypothesis that coronary heart disease patients have functionally abnormal preβ-1-HDL. Approach and Results- HDL cell-cholesterol efflux capacity via the ABCA1 and the SR-BI (scavenger receptor class B type I) pathways, HDL antioxidative capacity, apo (apolipoprotein) A-I-containing HDL particles, and inflammatory- and oxidative-stress markers were measured in a case-control study of 100 coronary heart disease cases and 100 sex-matched controls. There were significant positive correlations between ABCA1-dependent cholesterol efflux and the levels of small lipid-poor preβ-1 particles ( R2=0.535) and between SR-BI-dependent cholesterol efflux and the levels of large lipid-rich (α-1+α-2) HDL particles ( R2=0.712). Cases had significantly higher (87%) preβ-1 concentrations than controls, but the functionality of their preβ-1 particles (preβ-1 concentration normalized ABCA1-dependent efflux capacity) was significantly lower (-31%). Cases had significantly lower (-12%) mean concentration of large HDL particles, but the functionality of their particles (α-1+α-2 concentration normalized SR-BI-dependent efflux capacity) was significantly higher (22%) compared with that of controls. HDL antioxidative capacity was significantly lower (-16%) in cases than in controls. There were no significant correlations between either preβ-1 functionality or large HDL particle functionality with HDL antioxidative capacity or the concentrations of inflammatory- and oxidative-stress markers. Conclusions- HDL cell-cholesterol efflux capacity is significantly influenced by both the concentration and the functionality of specific HDL particles participating in cell-cholesterol efflux. Coronary heart disease patients have higher than normal preβ-1 concentrations with decreased functionality and lower than normal large HDL particle concentrations with enhanced functionality.