AI Ratio Research Articles

The Role of Paraoxonase-1 Activity, Apolipoprotein B Levels, and Apolipoprotein B/Apolipoprotein A-I Ratio as Risk Markers for Aortic Stenosis in Patients with a Bicuspid Aortic Valve

The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS in tricuspid aortic valve patients, the studies on the BAV population are lacking. We aimed to evaluate the association between selected lipid markers and the occurrence of AS in BAV patients. Methods: The study included 76 adults (21 female) with a BAV diagnosed by echocardiography, divided by age and AS diagnosis. Biochemical parameters concentrations in serum were measured: high density lipoprotein cholesterol (HDL-C) levels by standard enzymatic colorimetric tests, low density lipoprotein cholesterol (LDL-C) levels by the Friedewald formula, apolipoprotein A-I (Apo AI) and apolipoprotein B (Apo B) serum concentration by the nephelometric method, and paraoxonase-1 activity (PON-1 ASE) and arylesterase activity (PON-1 ARE) based on paraoxon and phenyl acetate hydrolysis. Results: A total of 54 patients (15 female) were more than 45 years old and 22 (6 female) were 45 or less years old. BAV patients with AS aged ≤45 had higher levels of Apo B, compared to those without AS [110.5 (102–132) vs. 95.6 (77–101) mg/d; p 0.044]. Similarly, Apo B/Apo AI ratio was higher in BAV patients with AS aged ≤45, compared to those without AS [(0.8 (0.7–1) vs. 0.6 (0.5–0.7); p 0.029]. In the group aged ≤45, Apo B showed a positive correlation with the aortic valve peak transvalvular velocity (AV Vmax) measurement (R Spearman 0.6, p 0.004). We found also that, among young BAV patients, those with AS had a lower level of PON-1 ARE compared to the cohort without AS [63.4 (52–80) vs. 85.3 (70–102); p 0.012]. We did not find any differences in lipid parameters in patients aged >45. Conclusions The metabolic link between Apo B level and Apo B/AI ratio with AS presence in BAV patients under 45 years of age suggests a significant impact of these parameters on the earlier development of AS in the BAV population. Molecules associated with high density lipoprotein and its antioxidant function, such as PON1, are valuable markers for AS development, compared to HDL-C and LDL-C levels.

Topochemical Modulations from 1D Iron Fluoride Precursor to 3D Frameworks.

Topochemical reactions are powerful pathways to modify inorganic extended structures, but the present approaches are limited by the degrees of freedom to tune the structural connectivity and dimensionality. In this work, we unveil a new topochemical bottom-up approach to tailor three-dimensional (3D) iron fluoride frameworks from the same one-dimensional (1D) FeF3.3H2O (IF) precursor upon reacting with iodide-based reagents (AI; A+ = Na+, K+, and NH4+). To elucidate their formation mechanism, a series of topochemical reactions are performed by varying the concentration of precursors, reaction temperatures, and durations, and their corresponding products are analyzed through X-ray diffraction, nuclear magnetic resonance, and Mössbauer spectroscopy techniques. Although the lower molar ratio of AI:IF (≈0.25:1.0) produces the same hexagonal tungsten bronze (HTB)-type AxFeF3, the topochemical reactions with higher AI:IF ratios yield weberite-Na1.95Fe2F7, tetragonal tungsten bronze (TTB)-K0.58FeF3, and pyrochlore-NH4Fe2F6 phases. Our density functional theory calculations attribute the formation of iron fluoride phases to their thermodynamic stability. Moreover, kinetics also play an important role in enabling weberite and HTB fluorides with high purity, while the pyrochlore-NH4Fe2F6 retains a minor HTB-(NH4)xFeF3 impurity. Overall, this work shows a new possibility of modulating the low-dimensional precursor to attain 3D frameworks with different structural arrangements via topochemical approaches.

Genetic and clinical factors underlying a self-reported family history of heart disease.

To estimate how much information conveyed by self-reported family history of heart disease (FHHD) is already explained by clinical and genetic risk factors. Cross-sectional analysis of UK Biobank participants without pre-existing coronary artery disease using a multivariable model with self-reported FHHD as the outcome. Clinical (diabetes, hypertension, smoking, apolipoprotein B-to-apolipoprotein AI ratio, waist-to-hip ratio, high sensitivity C-reactive protein, lipoprotein(a), triglycerides) and genetic risk factors (polygenic risk score for coronary artery disease [PRSCAD], heterozygous familial hypercholesterolemia [HeFH]) were exposures. Models were adjusted for age, sex, and cholesterol-lowering medication use. Multiple logistic regression models were fitted to associate FHHD with risk factors, with continuous variables treated as quintiles. Population attributable risks (PAR) were subsequently calculated from the resultant odds ratios. Among 166 714 individuals, 72 052 (43.2%) participants reported an FHHD. In a multivariable model, genetic risk factors PRSCAD (OR 1.30, CI 1.27-1.33) and HeFH (OR 1.31, 1.11-1.54) were most strongly associated with FHHD. Clinical risk factors followed: hypertension (OR 1.18, CI 1.15-1.21), lipoprotein(a) (OR 1.17, CI 1.14-1.20), apolipoprotein B-to-apolipoprotein AI ratio (OR 1.13, 95% CI 1.10-1.16), and triglycerides (OR 1.07, CI 1.04-1.10). For the PAR analyses: 21.9% (CI 18.19-25.63) of the risk of reporting an FHHD is attributed to clinical factors, 22.2% (CI% 20.44-23.88) is attributed to genetic factors, and 36.0% (CI 33.31-38.68) is attributed to genetic and clinical factors combined. A combined model of clinical and genetic risk factors explains only 36% of the likelihood of FHHD, implying additional value in the family history.

Predictive value of neutrophil-to-apolipoprotein A1 ratio in all-cause and cardiovascular death in elderly non-valvular atrial fibrillation patients

Neutrophil-to-apolipoprotein AI ratio’s (NAR’s) predictive value for the elderly non-valvular atrial fibrillation (NVAF) patients' death has not been fully recognized. We consecutively enrolled 1224 elderly patients with NVAF (≥75 years). With an average follow-up of 733.35 ± 271.39 days, 222 all-cause deaths were identified. Among these, 101 were caused by cardiovascular diseases. Cox regression showed that after correcting for potential confounders, patients in the Q4 group had an increased all-cause (hazard ratio [HR] = 1.90, 95% confidence interval [CI]: 1.20–2.99) and cardiovascular death (HR = 2.59, 95% CI: 1.30–5.15) risk compared to those in the lowest NAR quartile. Kaplan–Meier analysis indicated that all-cause and cardiovascular death were higher in the high NAR than those in the lowest NAR category (log rank, all, P < 0.001). A nonlinear association was observed between death and NAR. NAR may be a promising predictive biomarker for identifying elderly NVAF patients with poor clinical prognoses.

Data Management and Decision-Making Process Using Machine Learning Approach for Enterprises

Currently, Machine Learning (ML) seems very attractive since it may speed up business functions in enterprises, lower costs for supplying goods and services, and manage information to promote enterprise efficiency. Essential technological domains nowadays are the explosive period of growth in enterprise solutions, which are progressively used in almost all business platforms. The ML sessions will receive a thorough summary, and the relevant organizations will be shown procedures for relevant business processes. The data management unit is already been striving to solve related issues in ML applications for more than a generation, creating numerous customized analytical techniques. The approach described in the study uses a weighted directed graph displayed in an industrial environment to identify the core part of the neural network structure and then trains them using the relevant data source. The article proposed ML-assisted Enterprise Data Management (ML-EDM) for identifying the trade-off between ML growth in the financial sector and its consequences in precision and interpretability. According to the experimental findings, the ratio of AI for decision-making is 84.25%, the Speed and Agility proportion is 92.70%, the result of Earlier Prediction Management is 93.80%, the Infrastructure Development is 85.46%, with Data Efficiency is 84.5% and Performance efficiency of the system is 90.14%.

Early smoking initiation and changes in body weight, blood pressure and lipid profile in males: results of a 26-year prospective study

Aim. To study the relationship of early smoking initiation (adolescence) with changes in body weight, blood pressure (BP), and lipid profile in males within a prospective study. Material and methods. This paper presents the results of a 26-year follow-up of two groups: group 1 — males who began to smoke up to 17 years; group 2 — males who have not smoked until 17 years of age. The examination included a standard questionnaire, anthropometry, blood pressure measurement, determination of lipids and apolipoproteins (apo). Results. In males with an early smoking initiation, its prevalence by the age of 22 was 64,8%, and by the age of 43 it decreased to 41,7%. At 43, 60% of the original number of smokers continued to smoke. The relative risk for adolescents who started smoking before 17 years of age to be every day smoker at the age of 22, 33 and 43, respectively, was 2,2, 1,7 and 2,1 times higher than their peers who did not smoke before 17 years. With age, the prevalence of smoking decreased and its intensity increased (number of cigarettes smoked per day). At 33-43, in the group of early smoking initiation, compared with nonsmokers, there were higher values of body mass index, waist circumference, waist-to-hip ratio, systolic and diastolic blood pressure, triglycerides, low-density lipoprotein cholesterol, apo B, and apo B/apo AI ratio. Conclusion. Smoking initiation in adolescence is associated with an early adherence to smoking, higher prevalence in young adulthood and a high probability of continuation in adulthood. It also contributes to the general and abdominal obesity in adulthood and increases the atherogenicity of lipoprotein profile.

Lipids, apolipoproteins, and prognosis of amyotrophic lateral sclerosis.

ObjectiveTo determine whether lipids and apolipoproteins predict prognosis of patients with amyotrophic lateral sclerosis in a cohort study of 99 patients with amyotrophic lateral sclerosis who were diagnosed during 2015 to 2018 and followed up until October 31, 2018, at the Neurology Clinic in Karolinska University Hospital in Stockholm, Sweden.MethodsTotal cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein AI, apolipoprotein B, and lipid ratios were measured at the time of amyotrophic lateral sclerosis diagnosis or shortly thereafter. Death after amyotrophic lateral sclerosis diagnosis was used as the main outcome. The Cox model was used to estimate hazard ratios with 95% confidence intervals of death after amyotrophic lateral sclerosis diagnosis, after controlling for sex, age at diagnosis, site of symptom onset, diagnostic delay, body mass index, Amyotrophic Lateral Sclerosis Functional Rating Scale–Revised score, and progression rate.ResultsA 1-SD increase of total cholesterol (hazard ratio 0.60, 95% confidence interval 0.41–0.89, p = 0.01), low-density lipoprotein cholesterol (hazard ratio 0.64, 95% confidence interval 0.44–0.92, p = 0.02), low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (hazard ratio 0.65, 95% confidence interval 0.46–0.92, p = 0.02), apolipoprotein B (hazard ratio 0.62, 95% confidence interval 0.44–0.88, p = 0.01), or apolipoprotein B/apolipoprotein AI ratio (hazard ratio 0.61, 95% confidence interval 0.43–0.86, p < 0.01) was associated with a lower risk of death after amyotrophic lateral sclerosis diagnosis. A dose-response relationship was also noted when these biomarkers were analyzed as categorical variables.ConclusionsLipids and apolipoproteins are important prognostic indicators for amyotrophic lateral sclerosis and should be monitored at the diagnosis of amyotrophic lateral sclerosis.

Correlation of apolipoprotein levels with the severity of hyperlipidemic acute pancreatitis

Objective To explore the correlation of apolipoprotein levels with the severity of hyperlipidemic acute pancreatitis. Methods Clinical date of 169 patients with hyperlipidemic acute pancreatitis (AP) admitted in our hospital from September 2012 to December 2018 were retrospectively analyzed. Apolipoprotein (Apo) AⅠ, Apo B, Apo B/Apo AⅠ ratio were compared among hyperlipidemic AP patients with different severity. Pearson correlation analysis was conducted to explore the correlation of Apo AⅠ, Apo B, Apo B/Apo AⅠ with Atlanta classification, CTSI score, APACHE-Ⅱscore, RANSON score and C-reaction protein level. The optimal cut-off point of apolipoproteins for predict the severe hyperlipidemic AP was determined by ROC curve. The local and systemic complications of pancreatitis patients with different Apo levels were compared with chi-square test. Results There were no significant differences in general conditions among patients with severe AP (SAP), median-severe AP (MSAP) and mild AP (MAP). The Apo AⅠ levels of SAP [ (0.89±0.36) g/L] were lower than those of MSAP [(1.07±0.40)g/L, t=2.07, P=0.04] and MAP [(1.14±0.70) g/L, t=2.55, P=0.01]. Apo AⅠ was negatively correlated with Atlanta classification (r=-0.24, P 8 [70.59%(36/51) vs. 55.08%(65/118), χ2=3.56, P=0.04] in patients with Apo AⅠ≤0.8 g/L were higher than those in patients with Apo AⅠ>0.8 g/L. Conclusion Apolipoprotein AⅠ level is negatively correlated with Atlanta classification and Apo AⅠ level can be used to predict severity of hyperlipidemic acute pancreatitis. Key words: Pancreatitis; Hyperlipidemia; Apolipoproteins; APACHEⅡ; C-reactive protein

Haptoglobin Phenotype Modulates Lipoprotein-Associated Risk for Preeclampsia in Women With Type 1 Diabetes.

The incidence of preeclampsia (PE) is increased in women with diabetes (∼20% vs ∼5% in the general population), and first trimester lipoprotein profiles are predictive. Haptoglobin (Hp), a protein with functional genetic polymorphisms, has antioxidant, anti-inflammatory, and angiogenic effects. Among people with diabetes, the Hp 2-2 phenotype is associated with cardiorenal disease. To investigate whether Hp phenotype is associated with PE in type 1 diabetes mellitus (T1DM) and/or modulates lipoprotein-associated risks. Multicenter prospective study of T1DM pregnancy. Pregnant women with T1DM (normal albuminuria, normotensive at enrolment, n = 47) studied at three visits, all preceding PE onset: 12.3 ± 1.9, 21.8 ± 1.5, and 31.5 ± 1.6 weeks' gestation (mean ± SD). Hp phenotype and lipoprotein profiles in women with (n = 23) vs without (n = 24) subsequent PE. Hp phenotype did not predict PE, but lipoprotein associations with subsequent PE were confined to women with Hp 2-2, in whom the following associations with PE were observed: increased low-density lipoprotein (LDL) cholesterol, LDL particle concentration, apolipoprotein B (APOB), triacylglycerol/high-density lipoprotein (HDL) cholesterol ratio, and APOB/apolipoprotein AI (APOA1) ratio; decreased HDL cholesterol, APOA1, large HDL particle concentration, and peripheral lipoprotein lipolysis (all P < 0.05). In women with one or two Hp-1 alleles, no such associations were observed. In women with T1DM, although Hp phenotype did not predict PE risk, lipoprotein-related risks for PE were limited to those with the Hp 2-2 phenotype. Hp phenotype may modulate PE risk in diabetes.

GW29-e0424 Relationship between apolipoprotein B/apolipoprotein AI ratio and left ventricular ejection fraction in patients with stable angina pectoris

GW29-e0424 Relationship between apolipoprotein B/apolipoprotein AI ratio and left ventricular ejection fraction in patients with stable angina pectoris

Among young Sri Lankan patients with diabetes, how do lipid profiles differ between those with and without metabolic syndrome?

AimsMetabolic syndrome (MetS) is a risk factor for cardiovascular disease (CVD). Apolipoproteins are emerging as powerful predictors of CVD. We aimed to study associations of metabolic syndrome and apoB, apoAI, apoB/AI ratio in young Sri Lankans with type 2 diabetes. Materials & methodsBlood samples were available from 690 patients with type 2 diabetes in Sri Lanka Young Diabetes Study, and were analysed for apoB, apoAI, total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), triglycerides (TG) and glycated haemoglobin (HbA1c). Their associations with MetS as perNCEP/ATPIII criteria were studied. ResultsMetS was present in 60.9% of subjects. Of those with MetS, 76.0% were women. Those with MetS had higher apoB (1.27 V s 1.19 mmol/L; p = 0.001), apoB/AI (0.80 V s 0.75; p = 0.001), non-HDL cholesterol (NHDLC) (4.15 V s 3.98 mmol/L; p = 0.002),and triglycerides (1.51 V s 1.31 mmol/L; p < 0.001) and lower apoAI (1.58 V s 1.60 mmol/L; p = 0.03) and HDLC (1.02 V s 1.16 mmol/L, p < 0.001). ApoB and apoB/AIlevels increased significantly as the number of MetS components increased. ApoB and apoB:AI ratio were independently associated with MetS and components. ConclusionMetS showed a high prevalence among young Sri Lankans with diabetes. Elevated apoB is commonly clustered with other risk indicators in MetS.

Role of vitamin D3 level and Apo-B/Apo-A1 ratio in patients with unstable angina in Kerbala province, Iraq

Objectives Vitamin D deficiency may be responsible for endothelial dysfunction which in turn affects the onset and progression of coronary artery disease and its risk factors. The Apo B/Apo AI ratio indicates the balance between atherogenic and anti atherogenic particles, the higher the value, the higher is the cardiovascular risk. The aim of study is to find a possible association between unstable angina and vitamin D3, Apo A1, Apo B, and Apo B/Apo A1 ratio and other risk factors (age, body mass index and smoking).Methods This case-control study was conducted during the period from Nov. 2015 to Sep. 2016. A total of 40 patients of unstable angina presented with typical chest pain to the coronary care unit in Al-Hussein Teaching Hospital, Al-Hussein Medical City/ Kerbala. The diagnosis was based on the clinical history and electrocardiography. A total of 50 persons were matched in age, gender and BMI as a control group. The procedures were measured using Auto Immunoassay Analyzer.Results Vitamin D3 deficiency (&lt; 30 ng/mL) was prevalent in unstable angina (UA) compared with controls (vitamin D3 ≥ 30 ng/mL) (odds ratio [OR], 21.93; 95%, confidence interval [CI], 5.91–81.31; P &lt; 0.001). The results obtained that serum 25(OH) D3 was highly significant in smoker compared with non-smoker in both groups (P &lt; 0.001, P &lt; 0.05, respectively). The serum Apo B, Apo A1 and Apo B/Apo A1 ratio were highly significant between both groups (P &lt; 0.01, P &lt; 0.001, P &lt; 0.001, respectively). On the other hand, vitamin D3 recorded significant correlation with each of the age and BMI in control group (all P &lt; 0.01).Conclusion The present study showed a highly significant association between vitamin D3, Apo B, Apo A1 levels, Apo B/Apo A1 ratio and unstable angina as compared with the control group, and significant correlation between vitamin D3 and age, BMI and smoking.

Assessment of oxLDL, anti-oxLDL antibodies and lipoprotein-associated phospholipase A2 as cardiovascular risk markers in obese adolescents with and without T1DM

BackgroundOxidized low density lipoprotein (oxLDL), anti-oxLDL antibodies (oxLDL Ab) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are the sequel of lipoprotein oxidation and were not studied contemporarily in obese adolescents with and without type 1 diabetes (T1DM). Subjects and methodsThe current study enrolled seventy-five adolescents with T1DM who were selected as having hyperglycemia and seventy-five matched control subjects. Both the diabetic and the control groups were further divided into obese, normal weight and underweight subgroups according to body mass index (BMI). The following tests were performed: fasting plasma glucose (FG) glycated hemoglobin (HbA1c), insulin, apolipoprotein AI (apo AI), apolipoprotein B (apo B), oxLDL, oxLDL Ab and Lp-PLA2 mass. The diabetic subgroups were selected as having hyperglycemia. ResultsObese diabetic subgroup had higher insulin level and HOMA value than underweight and normal weight diabetic subgroups. oxLDL, oxLDL Ab and Lp-PLA2 showed higher concentrations in patients with T1DM than in control subjects (118.48±23.7, 1231.8±940 and 401.26±97.2vs. 58.1±17.9, 424.9±290.0 and 315.7±70; p<0.001).. In patients with T1DM, direct correlations were found between oxLDL, oxLDL Ab and Lp-PLA2 and cardiometabolic markers represented by apo B/apo AI ratio, FG and BMI. ConclusionThe current data provide evidence that oxLDL, its retroactive enzyme and antibody are present in circulation early in childhood when primed by obesity and hyperglycemia in T1DM and suggests that they could be useful markers for cardiovascular diseases (CVD).

Gamma-glutamyltransferase activity as a surrogate biomarker of metabolic health status in young nondiabetic obese women.

We investigated the association of gamma-glutamyltransferase (GGT) activity with atherogenic risk factors and metabolic health status in young nondiabetic obese women. In 140 obese women GGT activity was independently associated with BMI, triglyceride to high-density cholesterol ratio and homeostasis model assessment. Metabolically healthy but obese women had significantly lower GGT activity, associated with a normal insulin sensitivity, favorable lipid profile and apolipoprotein B to apolipoprotein AI ratio. GGT activity showed good diagnostic accuracy to distinguish between metabolically healthy but obese and obese women at risk (77.8% sensitivity and 60% specificity). GGT activity >17 U/l can predict atherogenic risk and insulin resistance. GGT activity may serve as a potential surrogate biomarker of atherogenic risk and metabolic health status.

Damascus kids’ slaughter, carcass and meat quality traits in different production systems using antioxidant supplementation

This study intended to investigate slaughter, carcass and meat quality characteristics of Damascus male kids reared under different production systems and antioxidant effect (Vit E). The kids, housed in pen groups and grazing groups, were equally divided for production systems and later each group was again equally divided for determination of Vit E effect. Production systems and Vit E were found to have no significant effect on slaughter and carcass traits. Differences between production systems were found significant for meat pH24, water holding capacity, cooking loss, tenderness, ether-extractable lipid and some color characteristics and concentrate feed supplemented with Vit E was effective on TBARS values. Each of the fatty acids except C18:2 n6 was affected by the production system but Vit E influence was superior on long-chain fatty acids. Grazing kids had a lower percentage of total SFA, n6, n6/n3, AI and TI ratio, while kids housed in pens had the lowest percentage of total UFA, NV and n3 ratio. On the other hand, kids that consumed supplemental Vit E had a higher percentage of total UFA, ratio of UFA/SFA, n3 and lower percentage of SFA, ratio of n6/n3, AI, TI compared to the kids fed by non-supplemental concentrate feed with Vit E. In accordance with the meat fatty acid composition, meat obtained from the kids that grazed and consumed supplemental Vit E was healthier than that of those housed in pen kids and non-supplemental Vit E consumed kids.

Abstract 112: Nitrated Apolipoprotein Ai/apolipoprotein Ai Ratio Is Increased in Diabetic Patients With Coronary Artery Disease

Recent studies indicated that protective function of HDL may be more representative than its concentration. Apolipoprotein AI (apoAI), the major protein of HDL, is nitrosylated in vivo to nitrated apoAI (NT-apoAI) that might cause dysfunction. We measured plasma NT-apoAI and apoAI levels in 777 patients with coronary artery disease (CAD) by ELISA, and found that median NT-apoAI/apoAI ratio was significantly higher in diabetes mellitus (DM) (n=327) versus non-diabetic patients (n=450). Further analysis indicated that DM, thiobarbituric acid-reactive substances and C-reactive protein levels were independent predictors of higher NT-apoAI/apoAI ratio. There was negative correlation between NT-apoAI/apoAI and use of anti-platelet and lipid lowering drugs. The cholesterol efflux capacity of plasma from 67 individuals with differing NT-apoAI but similar apoAI levels from macrophages in vitro was negatively correlated with NT-apoAI/apoAI ratio. In conclusion, higher NT-apoAI/apoAI ratio is significantly associated with DM in this relatively large German cohort with CAD and may contribute to associated complications by reducing cholesterol efflux capacity.

Increased monocyte turnover is associated with interstitial macrophage accumulation and pulmonary tissue damage in SIV-infected rhesus macaques.

We recently reported that increasing blood monocyte turnover that was associated with tissue macrophage death better predicts terminal disease progression in adult SIV-infected macaques than does declining CD4(+) T cell levels. To understand better mechanisms of pathogenesis, this study relates severity of lung-tissue damage to the ratio, distribution, and inflammatory responses of lung macrophage subsets during SIV infection in rhesus macaques exhibiting varying rates of monocyte turnover. In vivo BrdU incorporation was used to evaluate kinetics of monocyte/tissue macrophage turnover. Tissue damage was scored microscopically from H&E-stained lung-tissue sections, and cytokine expression was examined via immunohistochemistry and confocal microscopy. Increased monocyte turnover in SIV-infected rhesus macaques significantly correlated with severity of lung-tissue damage, as exhibited by perivasculitis, vasculitis, interstitial pneumonia, alveolar histiocytosis, foamy macrophages, multinucleated giant cells, fibrin, and edema in the alveoli. In addition, the higher monocyte turnover correlated with declining AI ratio, increased accumulation of IM in the perivascular region of the lung, and higher expression of IL-6 in the IM of the lung tissue exposed to a LPS, calcium ionophore, and tumor promoter combination stimulation ex vivo. Accumulation of IM associated with increasing monocyte turnover during SIV infection appears to contribute to chronic pulmonary inflammation and tissue damage during disease progression to AIDS.

Lipid and liver abnormalities in haemoglobin A1c-defined prediabetes and type 2 diabetes

Background and aimsWe aimed to investigate lipid abnormalities and liver steatosis in patients with HbA1c-defined prediabetes and type 2 diabetes compared to individuals with HbA1c-defined normoglycaemia. Methods and resultsNinety-one subjects with prediabetes according to HbA1c, i.e. from 5.7 to 6.4% (39–46mmol/mol), 50 newly diagnosed patients with HbA1c-defined type 2 diabetes (HbA1c ≥6.5% [≥48mmol/mol]), and 67 controls with HbA1c lower than 5.7% (<39mmol/mol), were studied. Fasting blood samples for lipid profiles, fatty liver index (FLI), bioimpedance analysis, ultrasound scan of the liver, and BARD (body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes) score for evaluation of liver fibrosis, were performed in all subjects. In comparison to controls, subjects with prediabetes were characterised by: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure, triglycerides levels and apolipoprotein B/apolipoprotein AI ratio, higher FLI, increased prevalence of and more severe hepatic steatosis, similar BARD score, and higher total body fat mass. In comparison to subjects with diabetes, subjects with prediabetes exhibited: similar blood pressure and apolipoprotein B/apolipoprotein AI ratio, similar FLI, reduced prevalence of and less severe hepatic steatosis, lower BARD score, increased percent fat and lower total body muscle mass. In comparison to controls, subjects with diabetes showed: lower apolipoprotein AI and HDL cholesterol levels, higher blood pressure and triglycerides levels, higher FLI, increased prevalence of and more severe hepatic steatosis, higher BARD score, and higher total body muscle mass. Moreover, HbA1c was correlated with BMI, HOMA-IR, triglycerides, HDL cholesterol, AST, and ALT. ConclusionsSubjects with HbA1c-defined prediabetes and type 2 diabetes, respectively, are characterised by abnormalities in lipid profile and liver steatosis, thus exhibiting a severe risk profile for cardiovascular and liver diseases.

Deleterious effect of glycation on the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium‐dependent vasorelaxation

Contrary to high-density lipoprotein (HDL) from normolipidaemic and normoglycaemic subjects, HDL from diabetic patients loses its ability to reverse the inhibition of vasorelaxation induced by oxidized low-density lipoprotein (LDL). The aim of this study was to analyze the role of glycation, a major abnormality observed in diabetes, on the impairment of the vasorelaxant effect of HDL. HDL from healthy subjects was glycated in vitro by incubation in glucose 200 mmol/L for 3 days. Vasoreactivity was evaluated by the relaxation response to acetylcholine of rabbit aorta rings pre-contracted with noradrenaline, before and after 2 h incubation with or without different lipoprotein fractions (Krebs buffer, oxidized LDL, normal or glycated HDL alone and with oxidized LDL). The fructosamine/apolipoprotein AI ratio was significantly increased in glycated HDL compared with native HDL (53.63 ± 7.91 vs 18.51 ± 4.10 µmol/g; p < 0.05). Oxidized LDL inhibited endothelium-dependent vasodilation compared with Krebs buffer [maximal relaxation (Emax) = 53.15 ± 6.50 vs 98.67 ± 2.07%, p < 0.001]. Native HDL was able to counteract the oxidized LDL-induced inhibition of vasorelaxation (Emax = 76.93 ± 5.41 vs 53.15 ± 6.50%, p < 0.001). On the other hand, glycated HDL had no effect on oxidized LDL-induced inhibition of endothelium vasorelaxation compared with incubation with oxidized LDL alone (Emax = 52.98 ± 2.07 vs 53.15 ± 6.50%, not significant). Glycation of HDL induces the loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on endothelium-dependent vasorelaxation, this is likely contributing to the impairment of antiatherogenic properties of HDL in diabetic patients.

The use of allelic imbalance to ascertain cis-regulation for human UGT2B7 in vivo

The use of allelic imbalance to ascertain cis-regulation for human UGT2B7 in vivo