Subclass Concentrations Research Articles

Impact of local and regional sources of PAHs on tribal reservation air quality in the U.S. Pacific Northwest

Atmospheric fine particulate matter (PM2.5) transports polycyclic aromatic hydrocarbons (PAHs) regionally and globally, influencing the air quality of communities around the planet. Concentrations of 130 PAHs extracted from PM2.5, collected on a Native American Tribal Reservation in the Northern Puget Sound region of the American Pacific Northwest, were used to assess the air quality impacts of regional and local PAH sources, atmospheric transport, and human health implications. Wind coming from the southeast of the sampling locations increased the overall PAH concentration of the PM2.5, while winds from the southwest decreased the PAH concentration. Concentrations of PAH subclasses increased or decreased independently at the two sampling locations with different changes in wind patterns, changing the excess lifetime cancer risk significantly. No long-range transport was measured, but emissions from local and regional PAH sources were measured. Samples collected during regional wildfires showed increased PAH concentrations. Samples collected during predicted weather inversions resulted in the highest PAH concentrations, and up to a ten-fold increase in excess lifetime cancer risk over the normal days.

Клиническое наблюдение пациента с хроническим риносинуситом и редкой формой первичного иммунодефицита

The article tentatively reviewed such rare immuno-dependent conditions as: IgG4-linked primary immunodeficiency (PI) and general variable immunodeficiency. Over the past two decades, more and more data has been accumulating about this subject, due to which several previously known nosological forms were combined into a new group of IgG4-associated diseases (IgG4-SZ), and in order to establish a diagnosis of IgG4-related systemic disease, two or more lesions of organs are required. This group of diseases has a common serological sign – an increase in the concentration of IgG4 subclass in serum. Histologically in organs and tissues, plasmocytes infiltration secreting IgG4, eosinophils are formed, fibrosclerosis and obliterating phlebitis develop. Laboratory and immunological examination of patients with PI helps to identify a specific violation of the immune system. Primary diagnosis is usually done using a panel of screening laboratory tests. A high risk of developing IgG4-C3 is in patients with pancreatitis with unknown etiology, sclerosing cholangitis, bilateral enlargement of the salivary and lacrimal glands, in the presence of multiple nodes in the lungs. Predisposing factors are middle age and male gender. The article presents a clinical observation of a patient suffering from a rare combination of primary immunodeficiency and chronic bilateral rhinosinusitis, special attention on laboratory and instrumental examinations and treatment.

Interesterification of a commonly consumed palm-based hard fat blend does not affect postprandial lipoprotein metabolism in healthy older adults

AbstractInteresterified (IE) fats are widely used to replace partially-hydrogenated fats as hard fats with functional and sensory properties needed for spreads/margarines, baked goods, and confectionary, while avoiding the health hazards of trans fats. Detailed mechanistic work to determine the metabolic effects of interesterification of commonly-consumed hard fats has not yet been done. Earlier studies using fats less commonly consumed have shown either neutral or a lowering effect on postprandial lipaemia. We investigated postprandial lipaemia, lipoprotein remodelling, and triacylglycerol-rich lipoprotein (TRL) fraction apolipoprotein concentrations following a common IE blend of palm oil/kernel fractions versus its non-IE counterpart, alongside a reference monounsaturated (MUFA) oil. A 3-armed, double blind, randomized controlled trial (clinicaltrials.gov NCT03191513) in healthy adults (n = 20; 10 men, 10 women) aged 45–75 y, assessed effects of single meals (897 kcal, 50 g fat, 16 g protein, 88 g carbohydrate) on postprandial plasma triacylglycerol (TAG) concentrations, lipoprotein profiles, and TRL fraction apolipoprotein B48 and TAG concentrations. Test fats were IE 80:20 palm stearin/palm kernel fat, the equivalent non-IE fat, and a high-MUFA reference oil (rapeseed oil, RO). Blood was collected at baseline and hourly for 8 h. Linear mixed modelling was performed, adjusting for treatment order and baseline values (ver. 24.0; SPSS Inc., Chicago, IL, USA). Total 8 h incremental area under the curves (iAUC) for plasma TAG concentrations were lower following IE and non-IE compared with RO (mean difference in iAUC: non-IE vs. RO -1.8 mmol/L.h (95% CI -3.3, -0.2); IE vs. RO -2.6 mmol/L.h (95% CI -5.3, 0.0)), but iAUCs for IE and non-IE were not significantly different. There were no differences between IE and non-IE for chylomicron fraction apoB48 concentrations nor TAG:apoB48 ratio. No differences were observed between IE and non-IE for lipoprotein (VLDL, HDL, LDL) particle size or sub-class particle concentrations. However, LDL particle diameters were reduced at 5 and 6 h following IE vs RO (P < 0.05). XXL- (including chylomicron remnants and VLDL particles), XL- and L-VLDL particle concentrations (average diameters > 75, 64, and 53.6 nm respectively) were higher following IE and non-IE vs. RO at 6 h (P < 0.05) and 8 h postprandially (P < 0.005–0.05). In conclusion, both IE and non-IE palmitic acid-rich fats generated a greater preponderance of pro-atherogenic large TRL remnant particles in the late postprandial phase relative to an oleic acid-rich oil. However, the process of interesterification did not modify postprandial TAG response or lipoprotein metabolism.

Variable Effects Of LDL Subclasses Of Cholesterol On Endothelial Nitric Oxide/Peroxynitrite Balance - The Risks And Clinical Implications For Cardiovascular Disease.

BackgroundElevated levels of low density lipoprotein (LDL), “bad cholesterol”, is not an accurate indicator of coronary disease. About 75% of patients with heart attacks have cholesterol levels that do not indicate a high risk for a cardiovascular event. LDL is comprised of three subclasses, with particles of different size and density. We used nanomedical systems to elucidate the noxious effects of LDL subclasses on endothelium.ExperimentalNanosensors were employed to measure the concentrations of nitric oxide (NO) and peroxynitrite (ONOO−) stimulated by LDL subclasses in HUVECs. N-LDL and ox-LDL (subclass A: 1.016–1.019 g/mL, subclass I: 1.024–1.029 g/mL, and subclass B: 1.034–1.053 g/mL) stimulated NO and ONOO− release. The concentrations ratio of (NO)/(ONOO−) was used to evaluate the noxious effects of the subclasses on endothelium.ResultsIn HUVECs, the (NO)/(ONOO−) ratio for normal endothelium is about 5, but shifts to 2.7±0.4, 0.5±0.1, and 0.9±0.1 for subclasses A, B, and I, respectively. Ratios below 1.0 indicate an imbalance between NO and ONOO−, affecting endothelial function. LDL of 50% B and 50% I produced the most severe imbalance (0.45±0.04), whereas LDL of 60% A, 20% B, and 20% I had the most favorable balance of 5.66±0.69. Subclass B significantly elevated the adhesion of molecules and monocytes. The noxious effect was significantly higher for ox-LDL than n-LDL.ConclusionSubclass B of “bad cholesterol” is the most damaging to endothelial function and can contribute to the development of atherosclerosis. Contrary to the current national guidelines, this study suggests that it’s not the total LDL, rather it is the concentration of subclass B in relation to subclasses A and/or I, that should be used for diagnosis of atherosclerosis and the risk of heart attack. By utilizing specific pharmacological therapy to address the concentration of subclass B, there is a potential to significantly reduce the risk of heart attack and atherosclerosis.

HIV infection drives IgM and IgG3 subclass bias in Plasmodium falciparum-specific and total immunoglobulin concentration in Western Kenya

BackgroundHIV infection is associated with more frequent and severe episodes of malaria and may be the result of altered malaria-specific B cell responses. However, it is poorly understood how HIV and the associated lymphopenia and immune activation affect malaria-specific antibody responses.MethodsHIV infected and uninfected adults were recruited from Bondo subcounty hospital in Western Kenya at the time of HIV testing (antiretroviral and co-trimoxazole prophylaxis naïve). Total and Plasmodium falciparum apical membrane antigen-1 (AMA1) and glutamate rich protein-R0 (GLURP-R0) specific IgM, IgG and IgG subclass concentrations was measured in 129 and 52 of recruited HIV-infected and uninfected individuals, respectively. In addition, HIV-1 viral load (VL), CD4+ T cell count, and C-reactive protein (CRP) concentration was quantified in study participants. Antibody levels were compared based on HIV status and the associations of antibody concentration with HIV-1 VL, CD4+ count, and CRP levels was measured using Spearman correlation testing.ResultsAmong study participants, concentrations of IgM, IgG1 and IgG3 antibodies to AMA1 and GLURP-R0 were higher in HIV infected individuals compared to uninfected individuals (all p < 0.001). The IgG3 to IgG1 ratio to both AMA1 and GLURP-R0 was also significantly higher in HIV-infected individuals (p = 0.02). In HIV-infected participants, HIV-1 VL and CRP were weakly correlated with AMA1 and GLURP-R0 specific IgM and IgG1 concentrations and total (not antigen specific) IgM, IgG, IgG1, and IgG3 concentrations (all p < 0.05), suggesting that these changes are related in part to viral load and inflammation.ConclusionsOverall, HIV infection leads to a total and malaria antigen-specific immunoglobulin production bias towards higher levels of IgM, IgG1, and IgG3, and HIV-1 viraemia and systemic inflammation are weakly correlated with these changes. Further assessments of antibody affinity and function and correlation with risk of clinical malaria, will help to better define the effects of HIV infection on clinical and biological immunity to malaria.

Pneumococcal vaccination responses in adults with subnormal IgG subclass concentrations

BackgroundWe sought to compare Pneumovax®23 responses in adults with subnormal IgG subclass concentrations. We studied adults with normal total IgG, frequent/severe respiratory infection, and subnormal IgG1, IgG3, or IgG1 + IgG3 before and after Pneumovax®23. We defined response as serotype-specific IgG > 1.3 μg/mL and aggregate response as IgG > 1.3 μg/mL for ≥70% of all serotypes tested. We compared patients with and without serotype-specific responses and performed logistic regression on aggregate responses using: age; male sex; body mass index; autoimmune condition(s); atopy; other allergies; subnormal IgGSc immunophenotypes; IgA; and IgM.ResultsThere were 59 patients (mean age 44 ± 13 (SD) years; 83.1% women). Median days between pre- and post-Pneumovax®23 testing was 33 (range 19–158). The median post-vaccination summated concentration of serotype-specific IgG was higher in patients with subnormal IgG1 than subnormal IgG3 (responders and non-responders). All subnormal IgG1 + IgG3 non-responders responded to serotypes 8, 9 and 26, unlike other non-responders. Subnormal IgG3 responders had lower responses to serotypes 1, 4, 12, 23, 26, and 51. Subnormal IgG3 non-responders had higher responses to serotypes 1, 3, 8, 9, 12, 14, 19, 51, and 56. Response rates decreased with increasing age. Aggregate responders were: subnormal IgG1, 54%; IgG3, 46%; and IgG1 + IgG3, 46%. Regression on aggregate response revealed lower response with male sex (odds ratio 0.09 [95% CI 0.01, 0.77]) and atopy (0.17 [0.03, 0.83]).ConclusionsSerotype-specific IgG responses to Pneumovax®23 were greater in patients with subnormal IgG1 than subnormal IgG3. Male sex and atopy were associated with lower aggregate responses.

Atorvastatin and Fenofibrate Increase the Content of Unsaturated Acyl Chains in HDL and Modify In Vivo Kinetics of HDL-Cholesteryl Esters in New Zealand White Rabbits.

Previous studies demonstrated modifications of high-density lipoproteins (HDL) structure and apolipoprotein (apo) A-I catabolism induced by the atorvastatin and fenofibrate combination. However, it remains unknown whether such structural and metabolic changes of HDL were related to an improvement of the HDL-cholesteryl esters (HDL-CE) metabolism. Therefore, we determined the structure of HDL and performed kinetic studies of HDL-CE radiolabeled with tritium in rabbits treated with atorvastatin, fenofibrate, and a combination of both drugs. The atorvastatin and fenofibrate combination increased the HDL size and the cholesterol and phospholipid plasma concentrations of the largest HDL subclasses. Moreover, the relative amount of unsaturated fatty acids contained in HDL increased, in detriment of saturated fatty acids as determined by gas chromatography–mass spectrometry. The transfers of cholesteryl esters (CE) from HDL to very low-density lipoproteins/low-density lipoproteins (VLDL/LDL) and vice versa were enhanced with atorvastatin, alone or in combination. Moreover, the direct elimination of CE from plasma via VLDL/LDL decreased with fenofibrate, whereas the direct elimination of CE via HDL augmented with the combination treatment. Taken together, the rise of unsaturated fatty acid content and the size increase of HDL, suggest that atorvastatin and fenofibrate induce more fluid HDL particles, which in turn favor an enhanced CE exchange between HDL and VLDL/LDL. Our results contribute to a better understanding of the relationship between the structure and function of HDL during the use of anti-dyslipidemic drugs.

CETP genotype and concentrations of HDL and lipoprotein subclasses in African-American men.

Aim: To assess the association between theCETP Taq1B and I405V polymorphisms with levels of lipoprotein subclasses in African-American (AA) men with and without Type 2diabetes (T2DM). Patients & methods: AA men, over 30 years of age, with (n=54) or without T2DM (n=50), and not receiving lipid-lowering agents, underwent advanced lipid analysis and genotyping. Results & conclusion: In the total patient population Taq1B B2-allele carriers had significantly higher levels of large HDL subclasses (HDL-2b [p=0.017] and HDL-L [p=0.019]), lower levels of small-HDL subclasses (HDL-3a [p =0.004] and HDL-3b [p=0.031]), and lower levels of LDL subclasses (LDL-IVa [p=0.012] and LDL-IIIb [p=0.009]). The only significant genotype-diabetes interaction occurred with the HDL-2a subclass (p=0.015). No statistically significant associations were seen with I405V genotype. Our observations of lower levels of small-HDL and higher levels of large-HDL suggest that a potentially important HDL subclass-CETP relationship exists.

Blood lymphocyte subpopulations in healthy water buffaloes (Bubalus bubalis, Mediterranean lineage): Reference intervals and influence of age and reproductive history

There is an increasing interest toward infectious diseases and mechanisms of immune response of water buffaloes, mainly because of the growing economic impact of this species and of its high-quality milk. However, little is known about the immune system of these animals in physiological conditions.Recently, a wide number of antibodies cross reacting with buffalo antigens has been validated for use in flow cytometry (FC), allowing detailed characterization of the lymphocytic population in this species.The aim of the present study was to describe the lymphocyte subpopulations in a large number of healthy water buffaloes, providing reference intervals (RIs), and to assess whether the composition of blood lymphocyte population significantly varied with age and reproductive history. Our final aim was to lay the ground for future studies evaluating the role of host immune response in water buffaloes.One-hundred-twelve healthy buffaloes from four different herds in the South of Italy were included in the study. All animals had been vaccinated for Infectious Bovine Rhinotracheitis (IBR), Salmonellosis, Colibacillosis and Clostridiosis, and all herds were certified Brucellosis- and Tuberculosis-free. Venous blood collected into EDTA tubes was processed for FC, and the percentage of cells staining positive for the following antibodies was recorded: CD3, CD4, CD8, CD21, TCR-δ-N24, WC1-N2, WC1-N3 and WC1-N4. Absolute concentration of each lymphoid subclass was then calculated, based on automated White Blood Cell (WBC) Count. Reference Intervals were calculated according to official guidelines and are listed in the manuscript.The composition of the lymphocyte population varied with age and reproductive history, with animals <2-years-old and heifers having higher concentration of most of the subclasses.The present study provides RIs for the main lymphocytic subclasses in healthy water buffaloes, highlighting gross differences between young and old animals. Establishment of age-specific RIs is recommended in water buffaloes. The data we present may be useful as a basis for further studies concerning mechanisms of immune response toward infectious agents in water buffaloes.

SAT-081 Advanced Lipoprotein Analysis Demonstrates Atherogenic Lipid Profile in Patients with Lipodystrophy That Improves after Metreleptin Treatment

Lipodystrophies (LD) are defined by deficient adipose tissue, causing low leptin and metabolic disease including severe insulin resistance and hypertriglyceridemia. Recombinant leptin (metreleptin, ML) treatment in LD improves insulin resistance and lowers triglycerides without changing HDL. Detailed measurement of lipoprotein particles using NMR spectroscopy can offer insights into cardiovascular disease (CVD) risk and lipid metabolism beyond a standard lipid panel and has never been performed in LD. We hypothesized that patients with LD would have a more atherogenic lipid profile than controls at baseline, which would be ameliorated with ML treatment secondary to improvements in insulin sensitivity. Patients with LD (N=17) were enrolled in a study evaluating short- and long-term effects of ML on metabolic disease and compared to 51 insulin sensitive (SI<3 on IV glucose tolerance test) sex-matched controls. Lipoprotein profiles were assessed on samples obtained after a 10-12 hour fast using a new deconvolution algorithm, LP4, which reports 27 triglyceride rich lipoprotein particles (TRLP) and 7 HDL particles (HDLP). The major categories are small, medium, and large HDLP and LDL particles (LDLP) and very small, small, medium, large, and very large TRLP. LP4 was compared in controls vs. patients with LD prior to ML. LP4 was compared in patients with LD before vs. after 14 days and 6 months of ML. Particle size, concentration, and concentration of subclasses by size were measured for LDLP, HDLP, and TRLP. Insulin sensitivity before and after ML was measured as glucose disposal (mg/kgFFM/min) during hyperinsulinemic euglycemic clamp. Patients and controls did not differ by age, weight, or BMI. Patients with LD had elevated large TRLP and smaller sized HDLP and LDLP, all associated with increased atherogenicity, vs. controls. Five of 17 patients with LD had chylomicrons present, vs. 0 of 51 controls. ML treatment in LD decreased size and concentration of TRLP, eliminated chylomicrons in all but 1 patient, decreased LDLP concentration, and increased LDLP size. ML treatment did not have major effects on HDLP. Prior to ML in patients with LD, insulin sensitivity negatively correlated with very large TRLP (r= -0.76, p= 0.0007), TRLP size (r= -0.52, p= 0.04), and TRLP TG (r= -0.58, p= 0.02). Short term (Day 0 to Day 14) and long-term changes (Day 0 to 6 months) in insulin sensitivity were not significantly correlated with changes in any lipoprotein parameter. In conclusion, patients with LD had an atherogenic lipoprotein profile at baseline consistent with increased CVD risk, which improved after ML treatment. The presence of fasting chylomicrons in a subset of patients with LD suggests saturation of chylomicron clearance by lipoprotein lipase. Improvements in lipoprotein parameters with ML were independent of improved insulin sensitivity, possibly due to direct effects of ML on lipoprotein metabolism.

MENOPAUSAL STAGE INFLUENCES LIPOPROTEIN SUBCLASS PROFILE IN HABITUALLY ACTIVE WOMEN

Menopause is associated with increased cardiovascular disease risk, in part due to worsening cholesterol profile with advancing menopausal stage. The effect of menopausal stage on lipoprotein cholesterol, lipoprotein particle size and number in active midlife women has not been evaluated.PURPOSETo evaluate differences in lipoprotein subclass concentrations between highly‐fit, habitually active women at distinct menopausal stages.METHODSWomen (40–65 yr) were healthy habitually active highly‐fit pre‐, peri‐, and postmenopausal women (PRE, n = 10, VO2peak = 47.0 ± 2.4 ml/kg/min, PERI, n = 12, VO2peak = 49.1 ± 2.4 ml/kg/min, and POST, n = 13, VO2peak = 43.8 ± 1.8 ml/kg/min). Menopausal stage was defined using the STRAW+10 criteria. Particle subclass concentrations and mean particle sizes (were measured using nuclear magnetic resonance spectroscopy (LabCorp). Calculated lipids (total triglyceride, total VLDL and chylomicron triglyceride, and total HDL cholesterol) were also analyzed. Blood samples for lipoprotein particle analysis were collected during days 1–6 of the menstrual cycle for PRE. ANOVAs with Holm‐Sidak post hoc testing were used to determine differences between groups for each lipid outcome. Nonparametric tests were employed if assumptions were not met. Data are presented as mean ± SEM.RESULTSThere was a significant effect of menopause stage on total HDL cholesterol (p = 0.010) with greater HDL cholesterol in POST (88.5 ± 2.2 mg/dl) vs. PRE (72.2 ± 5.7 mg/dl, p = 0.032) and total HDL particle concentration (p = 0.010) with significantly greater total HDL particle concentration in POST (40.2 ± 1.1 μmol/L) compared with PRE (34.9 ± 1.5 μmol/L, p = 0.023) and POST compared with PERI (PERI, 35.5 ± 1.3 μmol/L, p = 0.033). There was a trend for an effect of menopausal status on large HDL particle concentration (p = 0.072) with progressively greater large HDL particle concentration with each advancing stage (PRE 12.1 ± 1.1 μmol/L, PERI, 14.0 ± 1.2 μmol/L, POST, 15.5 ± 0.6 μmol/L). There was no significant effect of menopausal stage on medium or small HDL particle concentration or HDL size (all p&gt;0.05). There was an effect of menopausal stage on large LDL particle concentration (p = 0.039) with greater concentration of large LDL particles in PRE (479 ± 52.6 nmol/L) vs. POST (663 ± 47.5 nmol/L, p = 0.034) but no effect of menopausal stage on small LDL, IDL, or total LDL particle concentration, or LDL size (all p&gt;0.05). There was no effect of menopausal status on any VLDL &amp; chylomicron particle concentration or VLDL size (all p&gt;0.05).CONCLUSIONThese data indicate that in healthy, highly fit women, advancing menopausal stage does not have a negative effect on many lipoprotein particle concentrations. Habitual physical activity may eliminate or potentially reverse some of the negative consequences of menopause on lipids.Support or Funding InformationFunding Sources: American College of Sports Medicine Foundation Doctoral Student Research Grant (Serviente), National Institute on Aging Grant T32‐AG049676 (Pennsylvania State University), University of Massachusetts Amherst Provost's Undergraduate Research Fellowship (Chalvin).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Plasma Concentration of Immunoglobulin Classes and Subclasses in Children with Autism in the Republic of Macedonia: Retrospective Study

Plasma Concentration of Immunoglobulin Classes and Subclasses in Children with Autism in the Republic of Macedonia: Retrospective Study

Small HDL subclass is associated with coronary plaque stability: An optical coherence tomography study in patients with coronary artery disease

The role of high-density lipoprotein (HDL) subclasses in atherosclerotic diseases remains an open question. Previous clinical trials have attempted to explore the predictive effect of HDL subspecies on cardiovascular risk. However, no studies have assessed the connections between these subclasses and characteristics of plaque microstructure. To investigate the relationship of HDL subclasses and coronary plaque stability assessed by optical coherence tomography (OCT). Morphological characteristics of 160 nontarget lesions from 85 patients with coronary artery disease were assessed by OCT. HDL subclass profiles were analyzed using nondenaturing polyacrylamide gel electrophoresis. The plasma levels of small HDL subclass (percentage or concentration) were found to be positively associated with fibrous cap thickness (r=0.232, P=.007; r=0.243, P=.005) and negatively with maximum lipid arc (r=-0.240, P=.005; r=-0.252, P=.003) and lipid core length (r=-0.350, P<.001; r=-0.367, P<.001). Multivariate logistic regression analysis showed the small HDL subclass (percentage or concentration) (odds ratio [OR]: 0.457, 95% confidence interval [CI]: 0.214-0.974, P=.043; OR: 0.438, 95% CI: 0.204-0.938, P=.034) to be an independent factor in predicting OCT-detected thin-cap fibroatheroma of nontarget lesions. High levels of small HDL are associated with coronary nontarget plaque stability. Our findings suggest that the small HDL subtype might represent the atheroprotective activity of HDL.

Avocado Fruit on Postprandial Markers of Cardio-Metabolic Risk: A Randomized Controlled Dose Response Trial in Overweight and Obese Men and Women.

Avocados are distinctive fruits having both fats and fibers along with various micronutrients and bioactive phytochemicals. This study aimed to assess the effects of replacing carbohydrate energy in meals with half or whole avocado on postprandial indices of metabolic and vascular health. A single-center, randomized, controlled, 3-arm, 6 h, crossover study was conducted in overweight/obese middle-aged adults (n = 31). Participants consumed energy-matched breakfast meals containing 0 g (Control), 68 g (Half-A) or 136 g (Whole-A) fresh Hass avocado on 3 separate occasions. Post-meal glycemic (p < 0.0001), insulinemic (p < 0.0001) and flow mediated vasodilation (FMD) responses were reduced compared to Control meal (p < 0.01), independent of dose. Nuclear magnetic resonance analyses indicated lower concentrations of triglyceride-rich lipoproteins and higher concentrations of larger high-density lipoprotein (HDL) particles after the Whole-A vs. the Control meal (p = 0.02, p < 0.05, respectively). Race/ethnicity influenced sub-class lipoprotein concentrations (p < 0.05). Oxidized low-density-lipoproteins, monocyte chemoattractant protein-1, and interleukin-6 were not different among meals. Tumor necrosis factor-α tended to be lower after Whole-A vs. Control meal (p = 0.07). Replacing carbohydrate components with avocados in a meal improved FMD, a measure of endothelial function, and improved glycemic and lipoprotein profiles in overweight/obese adults. The study provides insight on the acute cardio-metabolic benefits of incorporating avocados into a meal.

Relationship between dietary quality, determined by DASH score, and cardiometabolic health biomarkers: A cross-sectional analysis in adults

The relationship between dietary patterns and cardiometabolic disease is of increasing interest. However, limited data regarding the association between dietary quality and biomarkers of cardiometabolic health exist. Therefore the aim of this work was to examine potential associations between dietary quality, assessed using the Dietary Approaches to Stop Hypertension (DASH) dietary quality score, adiposity and biomarkers of glucose homeostasis, lipoprotein metabolism and inflammation in a cross-sectional sample of 1493 men and women. Anthropometric measurements included BMI, hip and waist circumference (WC). Serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were determined. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance (NMR) spectroscopy. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Higher dietary quality was associated with lower BMI (P<0.05), WC (P<0.001), tumour necrosis factor α (TNF-α), interleukin 6 (IL-6), WBC and plasminogen activator inhibitor-1 (PAI-1) concentrations (P<0.01) and reduced insulin resistance (P<0.05). In addition less small low density lipoprotein (LDL) and small high density lipoprotein (HDL) particles and less large very low density lipoprotein (VLDL) particles were observed among those with better dietary quality (P<0.001). Individuals in the top DASH quartile had a 54% and 48% lower likelihood of central obesity and metabolic syndrome (MetS), respectively, than those in the lowest DASH quartile (P<0.05). Our data suggest that higher quality diet is associated with improved adiposity measures and a less insulin resistant, pro-inflammatory, pro-thrombotic and pro-atherogenic cardiometabolic profile which may impact on central obesity and MetS risk. These findings, which may be of clinical and public health significance in terms of dietary approaches to promote cardiometabolic health, warrant further examination.

Dietary Inflammatory Index and Biomarkers of Lipoprotein Metabolism, Inflammation and Glucose Homeostasis in Adults.

Accumulating evidence identifies diet and inflammation as potential mechanisms contributing to cardiometabolic risk. However, inconsistent reports regarding dietary inflammatory potential, biomarkers of cardiometabolic health and metabolic syndrome (MetS) risk exist. Our objective was to examine the relationships between a food frequency questionnaire (FFQ)-derived dietary inflammatory index (DII®), biomarkers of lipoprotein metabolism, inflammation and glucose homeostasis and MetS risk in a cross-sectional sample of 1992 adults. Energy-adjusted DII (E-DII) scores derived from an FFQ were calculated. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance (NMR) spectroscopy. Serum acute-phase reactants, adipocytokines, pro-inflammatory cytokines and white blood cell (WBC) counts were determined. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Our data indicate that a more pro-inflammatory diet, reflected by higher E-DII scores, was associated with potentially pro-atherogenic lipoprotein profiles characterised by increased numbers of large very low density lipoprotein (VLDL), small dense low density lipoprotein (LDL) and high density lipoprotein (HDL) particles and less large LDL and HDL particles (all p < 0.001). Inflammatory profiling identified a range of adverse phenotypes among those with higher E-DII scores, including higher complement component C3 (C3), C-reactive protein (CRP), (both p < 0.05), interleukin 6 (IL-6) and tumour necrosis factor (TNF)-α concentrations, higher WBC counts and neutrophil to lymphocyte ratio (NLR) and lower adiponectin levels (all p < 0.001). MetS risk was increased among those with higher E-DII scores (OR 1.37, 95% CI (1.01, 1.88), p < 0.05), after adjusting for potential confounders. In conclusion, habitual intake of a more pro-inflammatory diet is associated with unfavourable lipoprotein and inflammatory profiles and increased MetS risk.

No Overt Clinical Immunodeficiency Despite Immune Biological Abnormalities in Patients With Constitutional Mismatch Repair Deficiency.

Immunoglobulin class-switch recombination (CSR) and somatic hypermutations (SHMs) are prerequisites for antibody and immunoglobulin receptor maturation and adaptive immune diversity. The mismatch repair (MMR) machinery, consisting of homologs of MutSα, MutLα, and MutSβ (MSH2/MSH6, MLH1/PMS2, and MSH2/MSH3, respectively) and other proteins, is involved in CSR, primarily acting as a backup for nonhomologous end-joining repair of activation-induced cytidine deaminase-induced DNA mismatches and, furthermore, in addition to error-prone polymerases, in the repair of SHM-induced DNA breaks. A varying degree of antibody formation defect, from IgA or selective IgG subclass deficiency to common variable immunodeficiency and hyper-IgM syndrome, has been detected in a small number of patients with constitutional mismatch repair deficiency (CMMRD) due to biallelic loss-of-function mutations in one of the MMR genes (PMS2, MSH6, MLH1, or MSH2). To elucidate the clinical relevance of a presumed primary immunodeficiency (PID) in CMMRD, we systematically collected clinical history and laboratory data of a cohort of 15 consecutive, unrelated patients (10 not previously reported) with homozygous/compound heterozygous mutations in PMS2 (n = 8), MSH6 (n = 5), and MLH1 (n = 2), most of whom manifested with typical malignancies during childhood. Detailed descriptions of their genotypes, phenotypes, and family histories are provided. Importantly, none of the patients showed any clinical warning signs of PID (infections, immune dysregulation, inflammation, failure to thrive, etc.). Furthermore, we could not detect uniform or specific patterns of laboratory abnormalities. The concentration of IgM was increased in 3 out of 12, reduced in 3 out of 12, and normal in 6 out of 12 patients, while concentrations of IgG and IgG subclasses, except IgG4, and of IgA, and specific antibody formation were normal in most. Class-switched B memory cells were reduced in 5 out of 12 patients, and in 9 out of 12 also the CD38hiIgM− plasmablasts were reduced. Furthermore, results of next generation sequencing-based analyses of antigen-selected B-cell receptor rearrangements showed a significantly reduced frequency of SHM and an increased number of rearranged immunoglobulin heavy chain (IGH) transcripts that use IGHG3, IGHG1, and IGHA1 subclasses. T cell subsets and receptor repertoires were unaffected. Together, neither clinical nor routine immunological laboratory parameters were consistently suggestive of PID in these CMMRD patients, but previously shown abnormalities in SHM and rearranged heavy chain transcripts were confirmed.

Comparación de dos métodos para la cuantificación en suero de subclases de inmunoglobulinas

Background and aimThe quantification of serum immunoglobulins, and particularly of IgG and IgG subclasses, is of interest for the diagnosis of numerous diseases. The usual detection methods provide different results according to the analyser used. The aim of this study was to compare the results obtained with two different analysers in the measurement of the concentration of IgG and IgG subclasses. Material and methodsA total of 116 serum samples, regardless of the clinical diagnosis of the patients to whom the samples belonged, were analysed. The analyses were performed on a BNII® System (Siemens Healthcare GmbH, Germany) and Optilite® system (The Binding Site Group Ltd., Birmingham). ResultsThe correlation between total IgG concentration (mg/dl) and the sum of the individual IgG subclasses detected was higher using the Optilite® analyser (0.976 vs. 0.866). The percentage of agreement between assays ranged from 43% to 71%, with the lower limit being for the IgG3 agreement. An absence of the usual IgG subclass physiological proportion (IgG1>IgG2>IgG3>IgG4) was detected using BNII®. These findings were a due to the significantly lower proportion of IgG3 obtained by BNII® compared to Optilite® (P<.001), whereas the IgG4 concentration was not significantly different between analysers (P=.117). ConclusionsDifferences between the results obtained with the two different methods suggest that they should not be interchangeable, and that each clinical laboratory should only use one type of analyser. The reference ranges should be standardised according to the results obtained.

Replacement of Sedentary Time with Physical Activity: Effect on Lipoproteins.

Limited data on the relationship between physical activity and lipoprotein particle profiles exist. Our objective was to investigate associations between objectively measured physical activity and lipoprotein particle size and number, and specifically whether substituting daily sedentary behavior with light activity or moderate-to-vigorous physical activity (MVPA) is associated with beneficial alterations to the lipoprotein profile among adults and those at increased cardiometabolic risk (obese and insulin-resistant subjects). Sedentary behavior and physical activity intensity and duration were measured for 7 consecutive days using the GENEActiv accelerometer in a cross-sectional adult cohort (n = 396; mean age, 59.6 ± 5.5 yr). Lipoprotein particle size and subclass concentrations were determined using nuclear magnetic resonance spectroscopy. Isotemporal substitution regression modeling quantified the associations between replacing 30 min·d of sedentary behavior with equal amounts of light activity and MVPA on lipoprotein profiles. Daily duration of MVPA was inversely associated with large VLDL particles and lipoprotein insulin resistance scores (P < 0.05, after adjustment for sedentary time and other confounding factors). Reallocating 30 min of sedentary time with MVPA, but not light activity, was associated with less large VLDL particles resulting in more favorable average VLDL particle size and improved lipoprotein insulin resistance score (P < 0.05). Analysis of high-cardiometabolic-risk groups revealed similar beneficial alterations to VLDL profiles (P < 0.05) with substitution of sedentary time for MVPA among the insulin-resistant (homeostasis model assessment for insulin resistance ≥75th percentile) but not the obese (body mass index ≥30 kg·m) individuals. Daily MVPA duration and theoretical replacement of sedentary time with MVPA, but not light activity, were associated with less atherogenic VLDL profiles, particularly among the insulin-resistant individuals. These findings, which require further investigation, highlight the need to develop physical activity interventions aimed at improving atherogenic dyslipidemia and lowering cardiometabolic risk.

Serum lipoproteins are not associated with the severity of asthma

BackgroundAsthma is a chronic inflammatory disorder of the bronchi with a complicated and largely unknown pathogenesis. In this context, an emerging role is attributed to the apolipoproteins which serve as structural components of plasma lipoproteins. Low density lipoproteins (LDL) may be involved in the inflammatory pathways of the asthmatic airways; in particular, small dense LDL (sdLDL) particles were associated with increased oxidative susceptibility compared to medium and large sized LDL. In our previous study, we found a positive correlation between forced expiratory volume 1 s (FEV1) % predicted and larger LDL particles (LDL-1), and an inverse correlation between FEV1% predicted and sdLDL (LDL-3) in mild, untreated asthmatics. Although LDL appear to be important modulators of inflammation, data on their clinical implications are still lacking. ObjectiveThe aim of the study is to investigate whether LDL subclasses correlate with the severity of asthma, assuming that the atherogenic and most pro-inflammatory LDL contribute to ignite and perpetuate the airway inflammatory processes. MethodsThe study was conducted in one visit, and included clinical and lung functional assessments, as well as measurements of serum concentrations of the LDL subclasses. Non-denaturing, linear polyacrylamide gel electrophoresis was used to separate and measure LDL subclasses, with the LipoPrint© System (Quantimetrix Corporation, Redondo Beach, CA, USA). LDL subclasses were distributed as seven bands (LDL-1 to LDL-7), LDL-1 and -2 being defined as large LDL (least pro-inflammatory), and LDL-3 to 7 defined as sdLDL (most pro-inflammatory). Results70 asthmatics under inhaled treatment (M/F: 35/35) were enrolled; 10 healthy subjects (M/F: 3/7) served as controls. In the asthmatic group, FEV1% predicted was 81 ± 22% (mean ± SD), vital capacity (VC) % predicted was 97 ± 18%, and FEV1/FVC was 0.68 ± 0.1. The mean asthma control test (ACT) score was 18 ± 5. LDL-1 were significantly lower in asthmatics as compared to controls (18 ± 4% vs. 22 ± 4%, p = 0.008). On the contrary, LDL-2 (12 ± 4% vs. 12 ± 5%) and LDL-3 (3 ± 3% vs. 2 ± 2%) were not statistically different between the two groups; smaller subclasses were undetectable. To comply with the design of the study, subjects were classified according to their degree of severity into the 5 Global Initiative for Asthma (GINA) steps: Step 1 (M/F: 4/3, 44 ± 12 yrs), Step 2 (M/F: 1/2, 37 ± 11 yrs), Step 3 (M/F: 12/7, 47 ± 12 yrs), Step 4 (M/F: 8/15, 54 ± 12 yrs), and Step 5 (M/F: 7/9, 56 ± 9 yrs). None of the LDL subclasses showed significant differences between classes of severity: LDL-1 were 16.1 ± 5.6% in Step 1, 18 ± 2.8% in Step 2, 16.7 ± 3.7% in Step 3, 18 ± 3.3% in Step 4, and 19.5 ± 3.2% in Step 5 (p = NS); LDL2 were 14 ± 3.6%, 15 ± 3.4%, 12.4 ± 5.3%, 12.7 ± 4.4% and 11.3 ± 4.2%, respectively (p = NS); LDL3 were 5 ± 5.2%, 4.4 ± 2.6%, 3.3 ± 3.6%, 3.2 ± 2.6% and 2.4 ± 1.8%, p = NS. Finally, no relationship was detected between LDL subclasses and lung function parameters as well as the ACT scores. ConclusionsThe current findings confirm a role of LDL as a potential biomarker in the diagnostic process for asthma, and suggest that LDL cannot be used as marker of severity of the disease.