Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

Does non-alcoholic fatty liver impair alterations of plasma lipoproteins and associated factors in metabolic syndrome?

BackgroundHepatic steatosis (HS) is closely associated to metabolic syndrome (MS). Both, VLDL-triglyceride oversecretion and intrahepatic deposits, can take place. We evaluated VLDL characteristics, CETP, hepatic lipase (HL), IDL and small dense LDL (sdLDL), in patients with HS associated to MS.MethodsWe studied 3 groups matched by age and sex: 25 MS patients with HS (diagnosed by ultrasonography), 25 MS patients without HS and 25 healthy controls. Main measurements were: lipid profile, free fatty acids, VLDL composition, VLDL size by HPLC, CETP and HL activities, IDL-cholesterol and sdLDL-cholesterol.ResultsPatients with HS presented higher triglyceride levels, HOMA-IR and free fatty acids, VLDL mass and VLDL-apoB (p < 0.05). No differences in VLDL composition were observed. MS groups presented higher proportion of large VLDL than controls (p < 0.05). HS group showed higher CETP than controls (p = 0.01) and almost higher than MS without HS (p = 0.06). CETP correlated with VLDL-cholesterol content, r = 0.48, p < 0.005. The increase in sdLDL-cholesterol correlated with CETP (r = 0.47) and HL (r = 0.56), independent of insulin resistance (p < 0.003).ConclusionDespite intrahepatic fat, patients with HS secreted higher number of VLDL particles. CETP would have a remodeling action on VLDL in circulation, enriching it in cholesterol and also favoring, together with HL, the formation of sdLDL.     

Retinol binding protein 4 and insulin resistance in apparently healthy elderly subjects

BackgroundInsulin resistance (IR) increases with advancing age, yet the underlying mechanism is not well established. Although adipocytokine retinol binding protein 4 (RBP4) was recently shown to be linked to IR, their relationship remains controversial and relatively little information exists regarding their roles in the elderly subjects. We investigated the association between RBP4 and IR in obese and nonobese elderly subjects.MethodsA total of 111 (68 nonobese and 43 obese) apparently healthy elderly subjects, aged 75.9 ± 4.8 y were included. IR was determined by homeostasis model assessment (HOMA-IR). Serum RBP4 was measured by enzyme-linked immunosorbent assay.ResultsIn all subjects, RBP4 levels were positively correlated with fasting insulin, HOMA-IR, and triglycerides. However, after subgroup analysis, RBP4 levels were positively correlated with fasting glucose, fasting insulin, and HOMA-IR in the obese group only. In step-wise multiple linear regression analysis, RBP4 was found to be independently associated with triglyceride levels in the nonobese group and independently associated with HOMA-IR in the obese group.ConclusionsThe reason for the differing metabolic role of RBP4 in obese and nonobese elderly subjects remains uncertain, but our findings suggest that RBP4 may be linked to IR and lipid metabolism, at least in the elderly.     

Evaluation of a new homogenous method for detection of small dense LDL cholesterol: Comparison with the LDL cholesterol profile obtained by density gradient ultracentrifugation

BackgroundSmall, dense LDL (sdLDL) are highly atherogenic, and evidence indicates that sdLDL are useful predictors of cardiovascular disease. We evaluated a homogeneous method for the quantitative determination of sdLDL cholesterol (sdLDL-C) and compared it to the LDL-cholesterol profile obtained by density gradient ultracentrifugation (DGUC).MethodssdLDL-C was measured in plasma and in lipoprotein fractions obtained by DGUC using the sdLDL-EX “Seiken” kit.ResultssdLDL-C was only present in dense or intermediate LDL fractions obtained by DGUC. Plasma sdLDL-C levels were inversely corelated to the LDL relative floatation rate. The proportion of LDL-C that is sdLDL-C increases as a function of LDL density from a median of 19% for very buoyant LDL to 91% for very dense LDL particles. Plasma sdLDL-C level was significantly correlated with plasma triglyceride (TG) (n = 840, r_s = 0.710, p < 0.001). Among subjects with plasma TG > 150 mg/dl, 75% had sdLDL-C > 30 mg/dl, whereas among those with TG ≤ 150 mg/dl, only 17% had sdLDL-C > 30 mg/dl.ConclusionsThis precise and fully automated method for measuring plasma levels of sdLDL-C will allow the analysis of large number of samples in routine laboratories which will facilitate the evaluation of the clinical usefulness of sdLDL as a risk factor for CHD.     

Plasma ceruloplasmin as a biomarker for obesity: a proteomic approach

ObjectivesThis study aimed to investigate new biomarkers of obesity particularly in relation with inflammation-associated proteins using protein differential display techniques.Design and methodsComparison of protein expression in plasma between non-obese (n = 109, body mass index, BMI < 25 kg/m²) and obese (n = 32, BMI ≥ 25 kg/m²) groups was carried out using two-dimensional gel electrophoresis (2-DE) analysis. ELISA was also performed for validation.ResultsAmong six differentially expressed protein spots, ceruloplasmin (Cp) and fibrinogen were over-expressed in obese group. Plasma Cp levels were significantly higher in obese group than non-obese group (34.0 ± 8.6 vs. 41.3 ± 12.7 mg/dL, p < 0.001) and positively correlated with age (r = 0.253, p < 0.005), BMI (r = 0.265, p < 0.001) and hsCRP (r = 0.385, p < 0.001). In stepwise multiple linear regression analysis, plasma Cp along with hsCRP were found predictors for obesity (adjusted β-coefficient = 0.266, p < 0.01).ConclusionElevated plasma Cp levels were significantly associated with obesity, which may be suggested to be a marker of obesity.     

Association between an ASIC3 gene variant and insulin resistance in Taiwanese

BackgroundAcid-sensing ion channel 3 (ASIC3) is a ligand-gated cation channel activated by extracellular protons. ASIC3^?/? mice exhibit protection against age-dependent glucose intolerance with enhanced insulin sensitivity.MethodsTo determine the association between ASIC3 genetic polymorphisms and insulin resistance in Taiwanese, 606 unrelated subjects with no history of cardiovascular disease were recruited during routine health examinations.ResultsSix ASIC3 gene polymorphisms were genotyped and only the rs2288646 polymorphism was found associated with insulin resistance. Significantly lower fasting serum insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) index and significantly higher quantitative insulin sensitivity check index (QUICKI) were observed in subjects carrying the rs2288646-A allele than in the non-carriers (P = 0.028, P = 0.047 and P = 0.031, respectively) after adjustment for age, gender, and body mass index (BMI). Significantly lower frequencies of the rs2288646-A-containing genotypes were found in insulin resistant subjects (P = 0.023). By multivariate analysis, rs2288646 genotypes, age, BMI, fasting plasma glucose level, C-reactive protein level, and soluble intercellular adhesive molecule 1 level, were all independently associated with HOMA-IR index and QUICKI (all, P < 0.05).ConclusionsOur analysis indicated an independent association between an ASIC3 genetic polymorphism and insulin resistance in Taiwanese.     

Effects of a single dose of oral iron on hepcidin concentrations in human urine and serum analyzed by a robust LC-MS/MS method

BackgroundThe measurement of serum hepcidin, a peptide hormone that regulates iron metabolism, is clinically important to the understanding of iron homeostasis in health and disease. To date, the quantification of serum hepcidin levels by conventional immunological detection methods has proven problematic due to challenges in obtaining high quality antibodies which demonstrate good reproducibility. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been employed recently for more sensitive quantification of hepcidin; however, this method has high background levels and therefore less than optimal specificity.MethodsIn order to increase the specificity of the mass spectrometry based assay, we developed a robust, ultra-performance liquid-chromatography-tandem mass spectrometry (UPLC-MS/MS) protocol using multiple selected reaction monitoring (mSRM) for quantification of hepcidin levels in urine and serum of human subjects. With this assay, we assessed levels of hepcidin before and for up to 8 h after oral ingestion of ferrous sulfate in ten adult human subjects without known disease.ResultsThe linear response of hepcidin quantitation on each instrument was measured, and the correlation coefficients of these calibrations were r² = 0.9512 ± 0.0202 (n = 5) for urine and r² = 0.9709 ± 0.0291 (n = 5) for serum [r² = mean ± SD]. Compared to baseline, the levels of urinary hepcidin between 2–4 h and 4–8 h of both women and men showed significant increases with p < 0.05 and p < 0.001, respectively. The levels of serum hepcidin between 4 h and 8 h in both women and men showed significant increases, compared with baseline values, with both p < 0.01. Interestingly, we also observed some degree of oscillation of levels, occurring at later time points.ConclusionsWe have developed and validated a new method for measuring hepcidin concentrations in human serum and urine and used it to demonstrate early increases with iron supplement in both urinary and serum levels of hepcidin, which return to baseline levels, except in urine samples from men.     

Validation of the Taiwanese version of the Athens Insomnia Scale and assessment of insomnia in Taiwanese cancer patients

ContextIt is well known that insomnia is highly prevalent in cancer patients. Although various studies have used the Athens Insomnia Scale (AIS) for insomnia assessment, it has never been applied to cancer patients with insomnia.ObjectivesThe purpose of this study was to establish the reliability and validity of the Taiwanese AIS version (AIS-T) and evaluate the severity of insomnia among cancer patients in Taiwan.MethodsUsing a cross-sectional research design, 195 cancer patients (n = 195) were recruited from outpatient oncology clinics.ResultsCronbach’s alpha for internal consistency was 0.83, and the test-retest reliability was 0.94 over an interval of three days, based on a sample of 30 patients. Moreover, concurrent validity could be evaluated by significant correlations of the AIS-T with the Pittsburgh Sleep Quality Index-Taiwan form (PSQI-T) (r = 0.82, P < 0.001) and sleep efficiency measured by Actiwatch parameters (r = ?0.54, P < 0.001). Construct validity could be established by the Brief Fatigue Inventory-Taiwan form (r = 0.56, P < 0.001) and Medical Outcomes Study Short Form-36-Taiwanese version (physical component summary: r = ?0.52, P < 0.001; mental component summary: r = ?0.53, P < 0.001). The AIS-T could detect significant known-group validity from sleep quality (PSQI-T ≥5 or <5, respectively). The Actiwatch parameters are consistent with the results of the AIS-T, and both data sets indicate that patients experienced sleep disturbances. The prevalence of insomnia, as defined by the criteria of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 4th ed., was 22.56%; 49.2% subjects had significant insomnia at the score ≥6 at AIS-T.ConclusionThis study concludes that the AIS-T is a reliable and valid instrument for assessing insomnia among cancer patients in Taiwan.     

Pro-inflammatory and atherogenic circulating factors in non-alcoholic fatty liver disease associated to metabolic syndrome

BackgroundIt is not elucidated if liver fat deposits associated to metabolic syndrome (MS) aggravate the atherogenic state. We evaluated, in MS patients, if the presence of non-alcoholic hepatic steatosis (HS) determines differences in inflammatory markers and VLDL characteristics.MethodsSeventy-five patients with MS were divided into 2 groups depending on the presence or absence of HS, assessed by ultrasound. Lipid profile, free fatty acids (FFA), VLDL composition, adiponectin, tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), and soluble adhesion molecules (sVCAM-1 and sICAM-1) were measured.ResultsHS patients presented increased triglycerides levels, HOMA-IR and FFA. Patients with HS showed a reduction in adiponectin (p = 0.04) and increase in hs-CRP (p = 0.02), independently of insulin-resistance (IR). FFA correlated positively with TNF-α (p = 0.04) and inversely with adiponectin (p = 0.01). hs-CRP correlated with all inflammatory markers, independently of IR: TNF-α (r = 0.34, p = 0.02), sVCAM-1 (r = 0.29 p = 0.03), sICAM-1 (r = 0.56, p = 0.01), adiponectin (r = ?0.34, p = 0.04). HS patients presented higher VLDL mass and number of particles. Adiponectin correlated with VLDL cholesterol content (r = ?0.47, p = 0.04), independently of IR. VLDL, once secreted, would suffer from changes, becoming more atherogenic.ConclusionsSimple HS would play an important role increasing cardiovascular risk, independently of IR. hs-CRP may represent a useful biomarker of this condition.     

The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: the Korean Genomic Rural Cohort Study

BackgroundLeptin and adiponectin are adipokines, shown to have opposing functions for fat metabolism and development of metabolic syndrome. We determined if the ratio of serum leptin to adiponectin (L/A ratio) adjunctively contributes to the risk of metabolic syndrome beyond the homeostasis model assessment of insulin resistance (HOMA-IR).MethodsThis study included 1532 men and 1856 women, aged 40–70 y assessed in the Korean Genomic Rural Cohort Study from 2005 to 2008. The serum concentrations of adiponectin and leptin were measured by radioimmunoassay. Area under the receiver operating characteristic curve (AUROC) analyses were used to describe the ability of L/A ratio and HOMA-IR to differentiate between subjects with and without metabolic syndrome.ResultsThere were no significant differences in the ability of L/A ratio and HOMA-IR to predict metabolic syndrome (AUROC of L/A ratio vs. HOMA-IR, 0.771 vs. 0.774, p = 0.8006 for men; 0.677 vs. 0.691, p = 0.3088 for women). There was a significant adjunctive contribution by the L/A ratio, beyond that of HOMA-IR, to the risk of metabolic syndrome in men (p < 0.0001 with 0.028 increased AUROC) and women (p = 0.025 with 0.017 increased AUROC).ConclusionsThe L/A ratio provides significant adjunctive information to the risk of metabolic syndrome beyond HOMA-IR alone. The L/A ratio could be a good surrogate marker to assess metabolic syndrome.     

Serum Retinol-Binding Protein 4 (RBP4) and retinol in a cohort of borderline obese women with and without gestational diabetes

ObjectivesTo evaluate whether serum RBP4 correlates with gestational diabetes mellitus (GDM) in a cohort of borderline obese (BMI > 30) pregnant women.Design and methodsSerum RBP4 and retinol were measured in pregnant women with (n = 12) and without (n = 10) GDM.ResultsRBP4, retinol and RBP4:retinol molar ratio were not different between the groups and were not associated with markers of insulin resistance.ConclusionsGDM is not associated with RBP4 or retinol among borderline obese pregnant women.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

Lymphocytic enzymes and lipid peroxidation in patients with metabolic syndrome

ObjectivesMetabolic syndrome (MetS) is considered a state of chronic inflammation. This study aimed to ascertain selected parameters of purinergic and cholinergic systems related to glucose metabolism and inflammation, as well as _γ-glutamyltransferase (GGT) and N-acetyl-b-glucosaminidase (NAG) activities and lipoperoxidation in lymphocytes of patients with MetS.Design and methodsThe adenosine deaminase (ADA), dipeptidyl peptidase IV (DPP-IV), acetylcholinesterase (AChE), GGT and NAG activities, as well as thiobarbituric acid reactive substances (TBARS) levels were investigated in lymphocytes of patients with MetS (n = 38) and healthy volunteers (n = 41). We also evaluated the insulin levels, anthropometric measurements and routine biochemical analyses.ResultsADA (p < 0.05), DPP-IV and AChE (p < 0.0001) activities were higher in patients with MetS when compared to the control group. Furthermore, we observed correlations between ADA and DPP-IV activities (p = 0.0002; r = 0.5945), TBARS levels and ADA (p = 0.0021; r = 0.5172) and DPP-IV activities (p = 0.0022; r = 0.5010).ConclusionsOur findings showed that MetS might cause tissue distress that disturbed lymphocytic ADA, DPP-IV and AChE activities in response to inflammatory stimuli. These alterations evidence clinical abnormalities, since these enzymatic systems are able to regulate several aspects of adipose tissue function and inflammatory state of MetS and could be used successfully both for preventing and for halting the progression of MetS.     

HOMA-IR and non-HDL-C as predictors of high cholesteryl ester transfer protein activity in patients at risk for type 2 diabetes

Background and aimsMetabolic syndrome (MS) and type 2 diabetes are highly associated with an abnormal lipoprotein profile, which may be generated and accentuated by high cholesteryl ester transfer protein (CETP) activity. Given the difficulty in measuring CETP activity, the aim was to identify simple biochemical predictors of high CETP activity.Design and methodsEighty five subjects at risk for type 2 diabetes were classified according to the presence of MS. Lipoprotein profile, HOMA-IR and endogenous CETP activity were evaluated.ResultsAs expected, MS patients presented higher concentration of glucose, insulin, triglycerides and non-HDL-C and lower HDL-C levels. Moreover, MS patients exhibited increased HOMA-IR and CETP activity. Employing a ROC curve for MS, high CETP activity was defined as > 250% ml^? 1 h^? 1. The predictive variables of high CETP were non-HDL-C ≥ 160 mg/dl (OR = 11.1;95%IC = 3.3–38.2;p < 0.001) and HOMA-IR > 2.1 (OR = 4.4;95%IC = 1.3–14.8;p < 0.05).ConclusionsHigh non-HDL-C and insulin resistance were predictors for increased CETP activity which measurement is not accessible for clinical laboratories.     

Looking beyond polypharmacy: quantification of medication regimen complexity in the elderly

BackgroundPolypharmacy has been shown to influence outcomes in elderly patients. However, the impact of medication regimen complexity, quantified by the Medication Regimen Complexity Index (MRCI), on health outcomes after discharge of elderly patients has not been studied.ObjectiveOur aim was to test the convergent, discriminant, and predictive validity of the MRCI in older hospitalized patients with varying functional and cognitive levels.MethodsWe retrospectively applied the MRCI to the medication regimen of 212 hospitalized patients and assessed its validity.ResultsThe mean (SD) MRCI scores for medication regimens and number of medications at discharge were 30.27 (13.95) and 5.95 (2.40), respectively. The MRCI scores were strongly correlated with the number of medications (r = 0.94, P < 0.001) and the number of daily doses (r = 0.87, P < 0.001) and increased as the number of medications taken ≥3 times daily increased (27.35, 34.45, and 43.00 for none, 1, and 2 drugs, respectively; P < 0.001). Positive correlations were observed between the Cumulative Illness Rating Scale–Geriatrics score and both the number of medications and the MRCI score (r = 0.40, r = 0.46, P < 0.001, respectively). No relationship was found between MRCI scores and the number of medications and age, sex, and postdischarge medication modifications. Patients nonadherent to at least 1 drug were discharged with a higher MRCI score and higher number of medications compared with medication-compliant patients (33.3 and 7.0 vs 27 and 5.8, respectively; P < 0.01). An inverse correlation was found between overall adherence 1 month after discharge and the MRCI score (r = ?0.188, P = 0.028); however, no such correlation was found regarding the number of medications at discharge.ConclusionsThe MRCI showed satisfactory validity and good evidence of classifying regimen complexity over a simple medication count. The MRCI demonstrated application in clinical research and practice in the elderly. However, more studies are needed to investigate its advantage over the number of medications for identifying patients with complex medication regimens and directing interventions to simplify their medication regimen complexity.     

Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity

ObjectiveInsulin resistance and type 2 diabetes are associated with an increased risk of neurodegenerative diseases. Decreased brain-derived neurotrophic factor (BDNF) levels might play a role in the pathogenesis of neuropsychiatric disorders. The aim of our study was to estimate serum BDNF concentration in nonobese women divided into subgroups according to their insulin sensitivity.Design and methodsWe studied 46 young, healthy, nonobese women. Insulin sensitivity was estimated with the euglycemic–hyperinsulinemic clamp technique. Then, participants were divided into subgroups of high (mean, 12.79 ± 2.01 mg/kg fat-free mass/min) and low insulin sensitivity (mean, 7.33 ± 1.66 mg/kg fat-free mass/min).ResultsWe observed decreased serum BDNF concentration in women with low insulin sensitivity in comparison to high insulin sensitivity group (3306.11 ± 603.10 vs 4141.91 ± 755.37 pg/mL, p = 0.001). Serum BDNF was positively related to insulin sensitivity (r = 0.43, p = 0.003). This correlation remained significant after adjustment for other estimated parameters.ConclusionsSerum BDNF is decreased in young nonobese women with low insulin sensitivity. Early detection and prevention of insulin resistance might be useful in the prevention of neurodegenerative disorders.     

Plasma concentrations but not serum concentrations of brain-derived neurotrophic factor are related to pro-inflammatory cytokines in patients undergoing major abdominal surgery

ObjectivesTo investigate peripheral brain-derived neurotrophic factor (BDNF) concentrations in the perioperative period, their relationship with transforming growth factor-β1 (TGF-β1 tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-6 genetics.Design and methodsProspective, observational study. BDNF, TGF-β1, IL-6 and TNF-α were analysed at baseline (T0), 5 h (T1), 24 h (T2) and 5 days (T3) after surgery, in 21 patients. The IL-6 ? 174 G/C polymorphism was genotyped.ResultsSerum BDNF concentrations decreased (P = 0.048), correlated with TGF-β1 (r = 0.610 at T1, r = 0.493 at T2, r = 0.554 at T3). Plasma BDNF concentrations raised (P = 0.049), correlated with IL-6 and TNF-α at T1 (r = 0.495 and r = 0.441, respectively). BDNF response was predictable from TNF-α and IL-6 concentrations and the IL-6 ? 174 G/C genotype.ConclusionSerum and plasma BDNF concentrations could relate to platelet activation and inflammatory response, respectively. IL-6 genetics played a role in the BDNF acute response.     

Effects of V279F in the Lp-PLA2 gene on markers of oxidative stress and inflammation in Koreans

BackgroundA single nucleotide polymorphism (SNP), V279F, in the lipoprotein-associated phospholipase A₂ (Lp-PLA₂) gene is known to influence enzyme activity. It is unclear whether Lp-PLA₂ exerts pro- or antiatherogenic effects in humans. We investigated the interplay between V279F, Lp-PLA₂ activity, oxidative stress and inflammation.MethodsWe genotyped 2914 healthy Koreans (43–79 years) for the Lp-PLA₂ V279F and measured anthropometric parameters, lipid profile, fatty acid composition, lipid peroxides, inflammatory markers and Lp-PLA₂ levels.ResultsLp-PLA₂ activity was 24% lower in V/F subjects (n = 641) than in those with the V/V genotype (n = 2227). Enzyme activity was undetectable in F/F subjects. Lp-PLA₂ activity was positively correlated with LDL-cholesterol (r = 0.134, P < 0.001), ox-LDL (r = 0.064, P < 0.01), 8-epi-PGF_2α (r = 0.198, P < 0.001), free fatty acid (r = 0.082, P < 0.001), and fibrinogen (r = 0.112, P < 0.01) levels. Additionally, ox-LDL, 8-epi-PGF_2α, free fatty acid, and fibrinogen levels were positively correlated with hs-CRP. V279F was associated with LDL-cholesterol and arachidonic acid (AA) in serum phospholipid. F/F subjects had lower LDL-cholesterol than V/V subjects (V/V: 120.9 ± 0.69, V/F: 119.4 ± 1.26, F/F: 109.2 ± 4.84 mg/dl, P = 0.025). A significant association between the F/F genotype and increasing AA in serum phospholipids was found in subjects with high LDL-cholesterol (≥ 130 mg/dl) (P = 0.003) but not in those with low LDL-cholesterol (< 130 mg/dl). F/F subjects in the high LDL-cholesterol group had CRP concentrations about three times higher than those with V/V or V/F genotypes (V/V: 1.25 ± 0.09, V/F: 0.97 ± 0.12, F/F: 3.20 ± 0.88 mg/dl, P < 0.001).ConclusionsThe recessive effects of Lp-PLA₂ V279F on LDL-cholesterol and significant correlations between Lp-PLA₂ activity and LDL-cholesterol, 8-epi-PGF_2α and fibrinogen support a pro-oxidative or pro-atherogenic role for this enzyme. Paradoxically, the combination of the complete deficiency of Lp-PLA₂ activity and high LDL-cholesterol enhanced lipid peroxidation and inflammation.     

Association between self-reported sleep disturbance and other symptoms in patients with advanced cancer

ContextSleep disturbance (SD) is a significant source of distress for patients with cancer. Studies of patients with advanced cancer receiving palliative care to identify symptoms associated with the severity of SD are limited.ObjectivesIn this study, we sought to identify the symptoms measured by the Edmonton Symptom Assessment Scale (ESAS) that are associated with SD, as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary aims of the study were to determine the association between occurrences of SD with occurrences of other symptoms and screening performance of the ESAS-Sleep item against the PSQI.MethodsWe reviewed the completed ESAS and PSQI assessments of 101 patients with advanced cancer who were receiving palliative care and had been admitted to prospective clinical trials previously initiated by us. Patients with a PSQI score of ≥5 were considered to have an SD. The frequency and severity of the ESAS symptoms items, their correlation with each other, the PSQI score, and the screening performance of the ESAS-Sleep item were calculated.ResultsThe median age of patients was 60 years. Most were white non-Hispanic (73%), had lung or breast cancer (41%), and were diagnosed with SD (85%). The PSQI score was correlated with the ESAS items of pain (r = 0.27, P = 0.006), dyspnea (r = 0.25, P < 0.001), well-being (r = 0.35, P < 0.0001), and sleep (r = 0.44, P < 0.0001). Compared with patients without SD, those with SD were more likely to report pain (P = 0.0132), depression (P = 0.019), anxiety (P = 0.01), and a poorer sense of well-being (P = 0.035). An ESAS-Sleep item cutoff score of ≥3 (of 10) resulted in a sensitivity of 74% and a specificity of 73%.ConclusionSD is associated with increased frequency of pain, depression, anxiety, and a worse sense of well-being. These four symptoms should be assessed in all patients with advanced cancer with a complaint of SD. The ideal cutoff point of the ESAS-Sleep item for screening for SD is a score of ≥3. More research is needed to better characterize this frequent and distressing syndrome.     

Serum retinol binding protein 4 in patients with familial partial lipodystrophy

ObjectiveTo determine Retinol Binding Protein 4 (RBP4) levels in patients with Familial Partial Lipodystrophy (FPLD).MethodsTen patients with FPLD and a control group (9 patients) were selected to participate in the study.ResultsRBP4-log levels were lower in patients with FPLD in comparison to control group (1.52  ±  0.32 vs 1.84 ± 0.25, p = 0.029). A statistical trend was observed between Waist-to-Hip Ratio and RBP4-log (r = - 0.44, p = 0.054).ConclusionRBP4 levels are decreased in FPLD.