Markers Of Inflammatory Status Research Articles

The value of the systemic immune-inflammation index in assessing disease severity in autoimmune encephalitis

Background Autoimmune encephalitis (AE) is a group of autoimmune diseases targeting the central nervous system, characterized by severe clinical symptoms and substantial consumption of medical resources. Neuroinflammation plays a crucial role in disease progression, and detecting inflammatory responses can provide insights into disease status and disease severity. The systemic immune-inflammation index (SII), a novel marker of inflammatory status, has been rarely studied in AE. Methods Retrospective analysis of data from AE patients admitted to the First Affiliated Hospital of Zhengzhou University between January 2019 and September 2023 was conducted. Univariate analysis and logistic regression were used to assess the association between SII and patient severity. Nomograms for predicting AE severity were established, and receiver operating characteristic (ROC) curves, concordance index (C-index), calibration curves, and decision curve analysis were employed to evaluate predictive accuracy. Additionally, the Clinical Assessment Scale in Autoimmune Encephalitis (CASE) score was used to assess patient severity. Results This study enrolled 157 patients, of whom 57 were classified as severe according to the CASE score. SII, cerebrospinal fluid (CSF) cell counts, disturbance of consciousness, and behavioural abnormalities independently associated with the occurrence of severe cases. The C-index of the nomograms was 0.87, indicating strong association with disease severity, as supported by the calibration. Additionally, SII levels were highest within seven days of onset and decreased after one month. In subgroup analyses of different antibodies, SII also associations with severe cases in NMDAR encephalitis. Conclusions Higher SII levels are associated with an increased likelihood of developing severe AE, peaking within 7 days of disease onset and decreasing thereafter, potentially offering a prognostic marker to assess disease progression early in its course.

Daily glucose pattern and physical activity levels in cancer survivors: preliminary results from remote monitoring

Background: Cancer survivors have elevated risk for type 2 diabetes. Increasing physical activity improves glucose control. However, this evidence is majorly based on blood glucose metrics (e.g., glucose or hemoglobin A1c) at a single point in time. Little is known about the effect of physical activity on blood glucose changes throughout a day in cancer survivors. Thus, we tested the hypothesis that higher physical activity levels is associated with a more favorable daily glucose pattern in cancer survivors in free-living settings. Methods: This is a preliminary analysis of an ongoing randomized controlled trial (Project KNOWN) to examine the effect of physical activity on daily glucose pattern via continuous remote monitoring. A total of 11 cancer survivors were included in this analysis (90% female, 90% white, average age 62.5 years [range 44-76 yr], 67% obese, and 75% hypertension). Participants wore a wrist-worn accelerometer (for daily steps) and a blinded continuous glucose monitor (CGM; for daily glucose averages [interstitial glucose was measured at every 15 minutes] and daily frequency of glucose spikes [defined as glucose level >140 mg/dL]) for two weeks. Multilevel regression model was used to account for multiple observations within each individual and to separate the within-person (WP) and between-person (BP) effects. The WP effect represents deviation from one’s own mean on any given day, and the BP effect represents the individual mean deviation from the study sample mean. To explore moderating effect on the relationship between physical activity and daily glucose, inflammatory biomarkers, blood lipids, blood pressure and body fatness (DEXA scan) were measured. Results: At the WP level, participants with elevated (>4 mg/L) systemic C-reactive protein (marker of inflammatory status), on the day when they had higher-than-usual step count, their glucose average was also lower than their usual level ( p=0.04). At the BP level, daily steps were negatively associated with daily frequency of glucose spikes in participants with less severe hypertension, lower % gynoid fat, and higher android/gynoid ratio than others in the study sample (all p<0.05). Further, daily steps were negatively associated with daily glucose average in participants with higher trunk-to-total fat ratio than others (p<0.05). Discussion: This preliminary study demonstrated the use of data from wearable sensors to analyze intra- and inter-person variability in daily glucose patterns in cancer survivors. Results suggested the impact of physical activity on daily glucose patterns might differ by a person’s physiological status. Future research can further characterize meaningful daily glucose dynamics from CGM data in cancer survivors to better understand how physical activity may have downstream effect on their health outcomes. American Institute for Cancer Research. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pro-Atherogenic and Pro-Oxidant Diets Influence Semen and Blood Traits of Rabbit Bucks.

Many dietary factors can affect sperm traits. We compared the effect of diets rich in pro-oxidant (flaxseed oil) and pro-atherogenic (coconut oil) substances without added antioxidants on semen traits, using the rabbit as an animal model. Thirty rabbit bucks (8 months old) were fed three diets for 150 days: CNT (control) a standard diet; HA (high-atherogenic) standard diet + 3% coconut oil, and HO (high-oxidizing) standard diet + 3% flaxseed oil. Semen samples were collected weekly for the evaluation of qualitative traits (kinetics, viability) and the oxidative damage (MDA and cytokines). Blood was collected at the start (T0) and end (T8) of the experimental period for the assessment of the oxidative damage (MDA and isoprostanoids), lipid profile, and testosterone. A worsening of sperm kinetics and viability was recorded in the HA group. Lipid oxidation in seminal plasma, as well as isoprostanoids in blood (F3-IsoPs and F4-NeuroPs), increased in both the HO and HA groups. A high level of TNF-α, a marker of inflammatory status, was recorded in the seminal plasma of the HA group. The resulting outcomes were mainly attributable to the different fatty acid profiles (SFA vs. PUFA) of the diets, which modulated an inflammatory/oxidative response.

Could systemic immune inflammation index be a new parameter for diagnosis and disease activity assessment in systemic lupus erythematosus?

Systemic immune inflammation index (SII) has been used as a marker of inflammatory status in various diseases, but its role in systemic lupus erythematosus (SLE) is unknown. We aimed to investigate the role of SII in SLE and its association with disease activity and renal involvement. In this retrospective study, 76 patients with SLE were compared with 76 age- and gender-matched healthy control group in terms of SII, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR). SLE Disease Activity Index 2000 system (SLEDAI-2K) was used to divide the SLE patients into an inactive group (SLEDAI-2K < 9) and an active group (SLEDAI-2K ≥ 9). Correlations between the ratios and both disease activity and renal involvement were analyzed. SLE patients had a higher level of SII compared with controls. The ability of SII in predicting SLE (AUC = 0.626) was lower than NLR (AUC = 0.723) and PLR (AUC = 0.666). SII was positively correlated with C-reactive protein (r = 0.288. p = 0.01), but no association between SII and SLEDAI-2K scores was found. Significantly higher values of NLR, but not SII, were detected in patients with nephritis (p = 0.04). The best NLR cut-off value to predict SLE patients with nephritis was 2.32, with 78.5% sensitivity and 56.2% specificity. For the first, we demonstrated that SII level was elevated in patients with SLE. However, NLR is a better marker than SII in predicting SLE and could serve as an indicator of nephritis. Larger-scale studies should be carried out to confirm our results.

Red orange and lemon extract preserve from oxidative stress, DNA damage and inflammatory status in lambs

Oxidative stress causes several pathological conditions in farm animals by inducing a reduction in animal welfare and production with major economic losses for livestock. The standardised phytoextract obtained by red orange and lemon processing has antioxidant and anti-inflammatory activities. In this study we have investigated whether treating lambs for 40 days with red orange and lemon extract (RLE) was able to prevent the antioxidant and anti-inflammatory mechanisms, typically in newborn period. For this purpose, at the end of treatment, redox status was assessed in plasma using oxidative stress markers: malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities. Moreover, 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine was measured as a biomarker of DNA damage and finally, the markers of inflammatory status, interleukin (IL) 1β and 6, were measured in plasma by using an enzyme-linked immunosorbent assay (ELISA). Results showed that RLE-treated lambs improved antioxidant mechanisms as demonstrated by the increase in SOD, CAT and GPx activities and, furthermore, a significant reduction in oxidative stress-induced damage was demonstrated through MDA and 8-OHdG measurements. Moreover, RLE was also able to prevent the increase of pro-inflammatory cytokines concentration, such as IL- 1 β and IL 6. Results showed in the present paper demonstrate the potential beneficial effects of the RLE in lambs. HIGHLIGHTS Oxidative stress causes economic loss and welfare impairment in livestock. Several oxidative markers can be used to assess the redox status in plasma. The activity of some antioxidant enzymes increased in RLE treated lambs. A reduction of pro-inflammatory cytokines was recorded in RLE treated lambs.

Time to solve the puzzle of heart failure with preserved ejection fraction by biomarkers, echocardiography and cardiac magnetic resonance

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): HEART PRESERVED onbehalf HEART PRESERVED Background Heart failure with preserved ejection fraction (HFpEF) is now recognized as a major and growing public health problem worldwide. Clinical trials investigating different treatment strategies had disappointing results. Several biomarkers of inflammation, endothelial dysfunction, and myocardial fibrosis appeared to be promising in understanding HFpEF pathophysiology. Methods. We enrolled prospectively 94 patients with HFpEF in sinus rhythm (according to 2019 scoring system) (67 ± 9 yrs, 33 men). We evaluated them by 2D and speckle tracking echocardiography (STE). 80 patients had also a cardiac magnetic resonance (CMR) 1.5T evaluation. We measured LV ejection fraction (LVEF), mean E’ (E’m), E/E’ ratio, sPAP, left atrial volume indexed (LAVi), and global longitudinal stain by STE (GLS). By CMR we evaluated LVEFcmr, LV mass, T1 mapping with mean extracellular volume (ECVm), and pre-gadolinium mean times quantification (preGDT1m) as markers of myocardial fibrosis. All patients had NTproBNP and biomarkers for systemic inflammation (IL6, cystatin C, pentraxin-3, GDF15), endothelial dysfunction: soluble E -selectin, VCAM, von Willebrand factor (vWf), and myocardial fibrosis: Galectin-3. Results. LVEF was 60.5 ± 6 % and LVEFcmr 61 ± 6.6%. All parameters from the scoring system were as we expected: E’m = 7.6 ± 1.8 cm/s, E/E’ ratio = 11 ± 3.4, sPAP = 34 ± 8 mmHg, LAVi = 47 ± 11 ml/m2, GLS=-18.3 ± 2.9, and NTproBNP of 282 ± 294 pg/ml. NTproBNP significantly correlated with sPAP, LAVi, preGDT1m, ECVm, galectin-3, GDF15, and pentraxin-3 (all r &amp;gt; 0.4, p &amp;lt; 0.05). The best predictor for NTproBNP level was GDF15 (r = 0.4, r2 = 0.25, p = 0.001). LAVi significantly corelated with E/E’ ratio, sPAP, NTproBNP, galectin-3 (r &amp;gt; 0.4, p &amp;lt; 0.05). GLS correlated with LVEFcmr, LV mass, ECVm, preGDT1m, LAVi, E/E’ ratio, NTproBNP, GDF15, vWf, Eselectin, VCAM (all r = 0.4, p &amp;lt; 0.05). The best predictor model for GLS was LV mass, NTproBNP, E-selectine, and vWf (r = 0.67, r2 = 0.45, P &amp;lt; 0.001). sPAP was best predicted by a model composed by IL6, VCAM, LAVi (r = 0.5, r2 = 0.25, p &amp;lt; 0.001). E’m significantly correlated with vWf, GHD15, VCAM, LV mass, and preGDT1 (all r &amp;gt; 0.4, p &amp;lt; 0.05), but the best predictor model included only LV mass and GDF15 (r = 0.57, r2 = 0.32, P &amp;lt; 0.001). Galectin-3 significantly correlated with LAVi, preGDT1m, and NTproBNP, but the only predictor for galectin-3 level was preGDT1 (r = 0.4, r2 = 0.2, p = 0.007). Conclusions In HFpEF NTproBNP is significantly correlated with markers of inflammatory status, endothelial dysfunction, and fibrosis, but the level is mainly determined by inflammation (GDF15). Diastolic dysfunction parameters are mainly correlated with inflammatory and endothelial dysfunction biomarkers . Only LAVi was correlated with myocardial fibrosis. Sub-clinical systolic dysfunction is mainly determined by proinflamatory status and endothelial dysfunction, but not by fibrosis.

Correlation of serum C - reactive protein with clinical parameters in diabetic patients having chronic periodontitis before and after treatment

Background and Objectives: Chronic periodontitis is an infectious disease characterized by inflammation within the supporting tissues of the teeth, progressive attachment loss, and bone loss. C-reactive protein, are acute phase proteins monitored as a marker of inflammatory status. The present study was performed to determine whether presence of periodontitis and non-surgical periodontal therapy could influence the serum levels of CRP in type II diabetes mellitus disease patients. Materials and methods: A total of 60 subjects were selected for study. Venous blood samples were taken at base line and 3 months after non-surgical periodontal therapy for the type II diabetic patients with the clinical signs of chronic periodontitis (group I, n=30) and patients with chronic periodontitis having no diabetic mellitus (group II, n=30) to estimate serum C-reactive protein (CRP) level. Clinical parameters such as glycated hemoglobin (HBA1c ≥ 6.5% ), random blood sugar (RBS) and clinical periodontal parameters (Gingival Index, Probing pocket depth, Clinical attachment level and Plaque Index) for the group I and II were measured. Results: at base line, type II diabetes mellitus patients group I (T2DMCP) were compared to the non-diabetic patients with chronic periodontitis group II (NDMCP) based on the clinical periodontal parameters (GI,PPD, CAL and PI )scores and CRP level, HBA1c , (RBS) with the 3months after treatment. All the result was statically significant except for the GI and PPD scores at base line which was statically non-significant. The result also shows significant decrease in all the periodontal parameters and CRP level at base line as compared to 3months after treatment when group I was compared to group II while there was no significant change in the CRP level in group I and HBA1c in group II at base line as compared to 3months treatment. Conclusion: The present study concludes that total CRP level were decreased after non-surgical periodontal therapy.

Maternal Pre-Pregnancy Obesity Attenuates Response to Omega-3 Fatty Acids Supplementation During Pregnancy.

Maternal obesity is associated with adverse offspring outcomes. Inflammation and deficiency of anti-inflammatory nutrients like omega(n)-3 polyunsaturated fatty acids (PUFA) may contribute to these associations. Fetal supply of n-3 PUFA is dependent on maternal levels and studies have suggested that improved offspring outcomes are associated with higher maternal intake. However, little is known about how maternal obesity affects the response to n-3 supplementation during pregnancy. We sought to determine (1) the associations of obesity with PUFA concentrations and (2) if the systemic response to n-3 supplementation differs by body mass index (BMI). This was a secondary analysis of 556 participants (46% lean, 28% obese) in the Maternal-Fetal Medicine Units Network trial of n-3 (Docosahexaenoic acid (DHA) + Eicosapentaenoic acid (EPA)) supplementation, in which participants had 2g/day of n-3 (n = 278) or placebo (n = 278) from 19 to 22 weeks until delivery. At baseline, obese women had higher plasma n-6 arachidonic acid concentrations (β: 0.96% total fatty acids; 95% Confidence Interval (CI): 0.13, 1.79) and n-6/n-3 ratio (β: 0.26 unit; 95% CI: 0.05, 0.48) compared to lean women. In the adjusted analysis, women in all BMI groups had higher n-3 concentrations following supplementation, although obese women had attenuated changes (β = −2.04%, CI: −3.19, −0.90, interaction p = 0.000) compared to lean women, resulting in a 50% difference in the effect size. Similarly, obese women also had an attenuated reduction (β = 0.94 units, CI: 0.40, 1.47, interaction p = 0.046) in the n-6/n-3 ratio (marker of inflammatory status), which was 65% lower compared to lean women. Obesity is associated with higher inflammation and with an attenuated response to n-3 supplementation in pregnancy.

Comparative evaluation of C-reactive protein in peripheral blood of patients with healthy gingiva, gingivitis and chronic periodontitis: A clinical and particle-enhanced turbidimetric immuno-analysis.

Background:C-reactive protein (CRP), an acute-phase protein monitored as a marker of inflammatory status, has been identified as a major risk factor for various systemic diseases. It is a reliable marker to infectious burdens and/or inflammation. The aim of this study was to compare and evaluate the systemic levels of CRP in the serum sample of the patients with healthy gingiva, gingivitis, and chronic periodontitis.Materials and Methods:A total of 60 systemically healthy patients were selected and divided into three groups: Patients with healthy gingiva (Group A), patients with generalized gingivitis (Group B) and patients with chronic periodontitis (Group C). Peripheral blood was collected and high-sensitive (hs)-CRP levels were estimated in the serum samples by using the particle-enhanced turbidimetric immuno-assay technique using a commercially available kit.Results:The mean hs-CRP level in Group A recorded was 0.437 ± 0.216, Group B was 0.771 ± 0.384 and Group C was 2.285 ± 0.381. A significantly elevated hs-CRP level was found in Group C as compared with Group B and A (P < 0.05). However, a moderate, but statistically significant increase in the hs-CRP levels was observed in Group B as compared with Group A (P < 0.05). The percentage of patients with elevated levels of hs-CRP >2 mg/l was significantly higher in Group C.Conclusion:The patients with chronic periodontitis demonstrated a mean hs-CRP levels higher than the patients with gingivitis and with healthy gingiva. Furthermore, with the increasing inflammation, the hs-CRP levels increased proportionately.

670 nm LED ameliorates inflammation in the CFH−/− mouse neural retina

Para-inflammation in the neural retina is thought to contribute to the onset of some age-related retinal diseases. Continuous innate immune system activation, manifests in progressive chronic inflammation, macrophage invasion and cell loss, resulting in visual loss.We have previously shown that mitochondrial function is augmented following 670nm LED exposure, leading to reduced retinal inflammation. Here, it was asked whether 670nm LED regulates para-inflammation in an aged-related macular degeneration mouse model. Mutant CFH−/− mice were exposed to four 90s exposures over 2days for 1week and 8weeks. These regimes significantly reduced activated macrophage number, TNF-alpha and MIF protein expression levels. Immuno-reactivity to C3, C3b and calcitonin, all markers of inflammatory status were also altered. Finally, innate immune proteins, TLR 2 and 4, showed a marked decrease in protein expression.These findings support the notion that 670nm LED regulates innate immunity, alleviating inflammation in the neural retina of an age-related macular degeneration mouse model.

Estimate of CRP and TNF-alpha level before and after periodontal therapy in cardiovascular disease patients

IntroductionEpidemiological studies show that individuals with periodontitis have a radically amplified threat to develop cardiovascular disease. CRP& TNF-α, are acute phase proteins monitored as a marker of inflammatory status, which have been identified as a major risk factor for atherosclerotic complications. Elevated CRP & TNF-α level in periodontitis patients have been reported by several groups. The present study was performed to determine whether presence of periodontitis and periodontal therapy could influence the serum levels of CRP & TNF-α in cardiovascular disease patients.MethodsForty cardiovascular disease subjects participated in the study. They were classified into two groups. Group A (Control) where no periodontal treatment was given, Group B (Test) where periodontal treatment (scaling & root planing) was performed. Periodontal clinical parameters like OHI-S, probing pocket depth, were evaluated together with serum CRP, TNF-α, at baseline and reassessed after 8 weeks for all the subjects in both the groups.ResultsThe CRP & TNF-α levels in both the groups decreased but the decrease in the Group A was minimal and was not statistically significant (P > 0.05); whereas in Group B where periodontal therapy was performed, there was statistically significant decrease.ConclusionIt can be concluded from the study that there can be a possible causal relationship between pathogenesis of periodontal disease and CVD as inferred from the statistical significant outcome in the form of decreased inflammatory biomarkers after the periodontal treatment.

Increased prevalence of malnutrition and reduced lean body mass in overweight/obese kidney transplant recipients

Overweight and obesity are common in subjects after kidney transplantation. On the other hand, features of malnutrition are also frequently recognized in this group of patients. The aim of the study was to evaluate the prevalence of both abnormalities in a cohort of stable kidney recipients and to assess whether obesity precludes malnutrition in transplanted patients. We also investigated associations between the nutritional status, graft function and adipokines concentrations. The study was performed in 80 prevalent kidney transplant patients and in a control group which consisted of 23 healthy volunteers. Body composition (% of fat, lean body mass (LBM), water content) was measured by multifrequency bioelectrical impedance (Body Composition Manager). Nutritional status was determined by a 7–point Subjective Global Assessment (SGA), anthropometric measurements and s-albumin concentration. C–reactive protein (CRP), Il–6 and plasminogen activator inhibitor–1 (PAI–1) were used as markers of inflammatory status. Concentration of leptin, adiponectin and visfatin were measured by ELISA. Results: Mean age was 52.4±13.9 years (45 men and 35 women). Diabetes mellitus was present in 29% (n=23) of them. Mean time after transplantation (transplantation vintage) was 82.5±56.5 months (median=73 months). Mean eGFR was 41.7±14.9 ml/min (4 points MDRD), BMI was 25.7±4.2. Overweight was present in 41% of the patients and obesity in 14%. On the basis of SGA evaluation, signs of malnutrition were observed in 48% of the subjects. Malnutrition was present in 64% (21/33) of the overweight patients and in 91% (10/11) of the obese patients. Transplantation vintage was directly associated with fat mass and inversely associated with LBM. Malnourished patients (SGA) had a longer transplantation vintage. Adiponectin levels were significantly lower in transplanted patients as compared to controls. In multivariate analysis, leptin was an independent predictor of serum creatinine level and of eGFR.. The prevalence of concurrent signs of overweight/obesity and malnutrition in the kidney transplant recipients is high

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG

Testosterone levels decrease with age. This decline is steeper during “critical illnesses”. Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as “acute postoperative frailty”. We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels.

Markers of inflammatory status are associated with hearing threshold in older people: findings from the Hertfordshire ageing study

Age-related hearing loss is a common disabling condition but its causes are not well understood and the role of inflammation as an influencing factor has received little consideration in the literature. To investigate the association between inflammatory markers and hearing in community-dwelling older men and women. Cross-sectional analysis within a cohort study. The Hertfordshire Ageing Study. A total of 343 men and 268 women aged 63-74 years on whom data on audiometric testing, inflammatory markers and covariates were available at follow-up in 1995. Average hearing threshold level (across 500-4,000 Hz) of the worst hearing ear and audiometric slope in dB/octave from 500 to 4,000 Hz. Older age, smoking, history of noise exposure and male gender (all P < 0.001) were associated with higher mean hearing threshold in the worse ear in univariate analysis. After adjustment for these factors in multiple regression models, four measures of immune or inflammatory status were significantly associated with hearing threshold, namely white blood cell count (r = 0.13, P = 0.001), neutrophil count (r = 0.13, P = 0.002), IL-6 (r = 0.10, P = 0.05) and C-reactive protein (r = 0.11, P = 0.01). None of the inflammatory markers was associated with maximum audiometric slope in adjusted analyses. Markers of inflammatory status were significantly associated with degree of hearing loss in older people. The findings are consistent with the possibility that inflammatory changes occurring with ageing may be involved in age-related hearing loss. Longitudinal data would enable this hypothesis to be explored further.

What Is the Meaning of Homocysteine in Patients on Dialysis?

To evaluate the determinants of total plasma homocysteine levels and their relations with nutritional parameters, inflammatory status, and traditional risk factors for cardiovascular disease in renal failure patients on dialysis treatment. The study was conducted on 70 clinically stable patients, 50 of them on hemodialysis (70% men; 55.3 ± 14.5 years) and 20 on peritoneal dialysis (50% men; 62 ± 13.7 years). Patients were analyzed in terms of biochemical parameters (serum lipids, creatinine, homocysteine [Hcy], creatine-kinase [Ck], folic acid, and vitamin B(12)), anthropometric data, markers of inflammatory status (tumor necrosis factor-alpha, C-reactive protein, interleukin-6), and adapted subjective global assessment. The total prevalence of hyperhomocysteinemia (>15 μmol/L) was 85.7%. Plasma folic acid and plasma vitamin B(12) were within the normal range. Multiple regression analysis (r(2) = 0.20) revealed that the determinants of total Hcy were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Hcy was positively correlated with albumin and creatinine and negatively correlated with total cholesterol, high density lipoprotein cholesterol, folic acid, and vitamin B(12). The determinants of total Hcy in the study sample were type of dialysis, creatinine, Ck, folic acid, and total cholesterol. Evidently, the small sample size might have had an effect on the statistical analyses and further studies are needed. However, Hcy in patients on dialysis treatment may not have the same effect as observed in the general population. In this respect, the association between malnutrition and inflammation may be a confounding factor in the determination of the true relationship between Hcy, nutritional status, and cardiovascular risk factors in this group.

Serum neutrophil gelatinase-B associated lipocalin (NGAL) levels in Down’s syndrome patients

Neutrophil gelatinase-associated lipocalin (NGAL) is a group of proteins with different functions.NGAL is released by different cell types such as epithelial cell, hepatocytes and renal tubular cells during inflammation and after cell injury. Expression of NGAL is induced under various pathophysiological conditions such as infection, cancer, inflammation, kidney injury, cardiovascular disease, burn injury, and intoxication, which has an important anti-apoptotic and anti-inflammatory role.Subjects with Down’s syndrome (DS) are affected by many pathological age related conditions such as mental retardation, Alzheimer’s disease, immune defects and increased susceptibility to infections. The aim of this study is to evaluate possible use of NGAL as a marker of inflammatory status for allow an early diagnosis of inflammatory disease such as autoimmune disease in DS patients, that are more susceptible to these pathologies, especially in elderly subjects.In this study were recruited 3 groups of DS subjects (children, adults and elderly) and compared them to healthy control group.The molecules of interest was determinated by immuno-enzymatic assay (ELISA).Our results show that NGAL plasmatic level was significantly higher in DS patients compared to healthy controls. Moreover NGAL levels increase in correlation with the age, and showed a significantly correlation between the increase with the severity of disease.DS is characterized by an enhancement of gene production such as GART, SOD-1 and CBS that encode specific protein and enzyme involved in hydrogen peroxide and superoxide production, species highly cytotoxic implicated in inflammation and ageing.NGAL may have the potential application to ameliorate the toxicity induced by oxidative stress conditions such as Alzheimer’s disease, thalassemia, cardiovascular disease, burn injury, transplantation, diabetes, and aging.

Blood and milk immune and inflammatory profiles in periparturient dairy cows showing a different liver activity index

This paper reports the results of a study that aimed to assess whether liver functionality defined by liver activity index (LAI) is associated with inflammatory and immune parameters in blood and milk. LAI is an index including the average blood levels of albumin, lipoproteins and retinol-binding protein measured three times in the first month of lactation (at 5, 15 and 30 days in milk). The aim was to assess the relationship of this index with blood and udder immune and inflammatory status as a means of identifying as early as possible cows at risk of disease. The research was carried out using 10 multiparous Italian-Friesian dairy cows of average genetic merit. Cows were retrospectively ranked in three groups according the LAI level. Blood samplings were performed at different intervals before and after calving; quarter milk samples were taken only after calving with the same schedule as blood samples. Leucocytes, oxidative burst, blood lysozyme and N-acetyl-beta-d-glucosaminidase (NAGase) curves showed large overlapping among the three LAI group curves during the follow-up period. Four blood (complement, sialic acid, haptoglobin and reactive oxygen metabolites) and three milk (somatic cell count, lysozyme and NAGase) parameters showed larger and more consistent differences among LAI groups. Complement showed higher values and sialic acid showed lower values in high LAI group when compared with the other two LAI groups. Two other markers of inflammatory status (haptoglobin and reactive oxygen metabolites) showed the lowest values in high LAI cows. A consistent and significant reduction of milk NAGase and milk lysozyme in high LAI group was observed. The results suggest that cows with the highest liver functionality index have also the highest levels of some immune markers and the lowest levels for inflammatory markers at blood (already before calving) and mammary levels. Finally, cows with low LAI index, being more susceptible to metabolic and infectious diseases, should be carefully monitored to identify as early as possible the development of a disease.

Low Albumin, High Ferritin, and Thrombocytopenia Before Transplant Predict Non-Relapse Mortality (NRM) Independent of the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI).

Abstract 651In 2005, the HCT-CI was reported as a weighted scoring system to evaluate pretransplant comorbidities and their effect on HCT outcomes. Among the general population or among patients (pts), serum albumin inversely correlates with age, smoking, obesity and hypertension; serves as a marker of inflammatory status; and predicts cardiovascular as well as all-cause mortalities. High serum ferritin concentration can indicate iron overload and is thought to predict morbidity and mortality after HCT. Cytopenia could indicate either progressive malignancy or extensively treated bone marrow. Here, we investigated 1) whether any of these three laboratory parameters independently impact NRM and 2) the possibility of incorporating these parameters into the HCT-CI to augment its predictive power. To this end, we collected data from 1448 pts with hematological malignancies treated with allogeneic HCT at a single institution. Proportional hazards models were used to estimate the hazard ratio (HR) for NRM associated with different cut-off values for serum albumin, ferritin, platelet count, hemoglobin, and absolute neutrophil count (Table 1). The models were adjusted for age (59% <50 vs 41% ≥50 years), disease type (69% myeloid vs 31% lymphoid), disease risk (47% low vs 53% high), recipient CMV sero-status (45% negative vs 55% positive), donor type (58% related vs 42% unrelated), conditioning regimen type (30% nonablative vs 70% ablative), and HCT-CI scores (36% “0” vs 16% “1” vs 18% “2” vs 16% “3” vs 15% “≥4”). All five laboratory parameters were predictive of NRM at most of the tested cutoff values (Table 1). We selected a single cutoff value for each of the five based on the highest statistical significance and prevalence and conducted another proportional hazard model where the effect of each parameter was adjusted for the effects of all others. In the final multivariate analysis, serum albumin <3.5 g/dl (HR 1.4, p=0.003), serum ferritin >1000 ng/ml (HR 1.4, p=0.03), and platelet count <100,000 /mm3 (HR 1.68, p<0.0001) independently predicted NRM among all pts, while neutrophil count <1000 /mm3 (HR 1.1, p=0.48) and hemoglobin <10 g/dl (HR 1.01, p=0.96) did not. The first 3 parameters were associated with statistically significantly higher NRM and worse survival among all pts and with strata based on the type of conditioning regimen (Table 2). Since the HR's for the first 3 parameters were less than 2, each parameter was assigned a weighted score of 1 for augmentation of the HCT-CI. At 2-years, overall survival rates were 79%, 64%, 52%, 47%, and 30% for the augmented HCT-CI scores of 0-1 vs 2 vs 3 vs 4 vs ≥5, respectively, suggesting preserved good linearity for outcome prediction. Serum albumin, ferritin, and platelets are simple, reliable, and important prognostic markers that should be assessed before allogeneic HCT, incorporated into risk-assessment, and prospectively validated for possibility of augmenting the performance of the HCT-CI.Table 1:Prevalence and association of pretransplant laboratory values with NRMCutoff values% of ptsHR1P1Albumin <3.530%1.57<0.0001Albumin <3.010%1.310.11ANC <150031%1.280.03ANC <100019%1.430.005ANC <50010%1.460.02Platelets <100,00035%1.85<0.0001Platelets <50,00017%1.490.003Platelets <20,0005%1.460.08Hgb <1022%1.320.02Hgb <98%1.140.45Ferritin >100011%1.710.0002Ferritin >25002%2.060.0011Adjusted for age, malignancy type, disease risk, pt CMV sero-status, donor type, conditioning regimen, and HCT-CI scoresTable 2:Differences in outcome according to pretransplant albumin, ferritin, and plateletsNRM at 2-yearsAll ptsAblativeNonablative%P%P%PAlbumin ≥3.518<0.000118<0.0001170.02Albumin <3.5283124Platelet count ≥100,00015<0.000114<0.000115<0.0001Platelet count <100,000333430Ferritin ≤100019<0.000119<0.0001190.10Ferritin >1000383930Survival at 2-yearsAlbumin ≥3.567<0.000168<0.0001640.0003Albumin <3.5454643Platelet count ≥100,00069<0.000170<0.000167<0.0001Platelet count <100,000444835Ferritin ≤100063<0.000165<0.0001580.005Ferritin >1000394230 Disclosures:No relevant conflicts of interest to declare.

Serum Concentration of Amino Acids Versus Nutritional Status in Hemodialysis Patients

The aim of this study was to evaluate the correlation between the serum concentration of amino acids (AAs) and nutritional status in hemodialysis (HD) patients. This study was performed in 22 HD patients dialyzed for 10 to 288 months, and in a control group of 20 healthy volunteers. Nutritional status was determined by the subjective global assessment method and by measuring albumin concentration. Body composition was determined using the parameters of body mass index, and the percentage of body fat and lean body mass (as measured by the near-infrared method). We measured C-reactive protein (CRP) as a marker of inflammatory status. Serum concentrations of 20 AAs were measured by precolumn orthophtalaldehyde derivatization, applying high-performance liquid chromatography (Hitachi-Merck HPLC, Tokyo, Japan) equipped with a C-18 reversed-phase column and a methanol/acetate buffer gradient. Thirteen of 22 (59%) patients were of good nutritional status, and 9/22 (41%) were malnourished, including 1 person with severe malnutrition. In dialyzed patients compared with control subjects, a decreased concentration of essential and nonessential AAs was observed (P < .05). Concentrations of the majority of studied AAs (16 out of 20) were lower in patients dialyzed for a period >2 years, compared with patients dialyzed for a shorter time. The ratio of branched-chain amino acids (BCAAs) to aromatic AAs was lower in the dialyzed group compared with control subjects. This ratio was also lower in patients dialyzed longer compared with patients dialyzed for <2 years. No correlation between the concentration of some AAs and CRP level or dialysis adequacy was observed. In the malnourished group, an insignificantly lower concentration of some essential AAs (lysine, leucine, isoleucine, valine, and threonine), and a significantly higher (P = .04) concentration of CRP, were observed. Despite quite good nutritional status, dialyzed patients present abnormalities in their AA profiles. Moreover, a significant decrease of BCAA concentration is related to calorie-protein malnutrition, inflammation, and a long period of hemodialysis.

Effect of ultrasmall superparamagnetic iron oxide nanoparticles (Ferumoxtran-10) on human monocyte-macrophages in vitro

Ferumoxtran-10, a dextran-coated ultrasmall superparamagnetic iron oxide particle, has the potential to reveal macrophages in vivo using magnetic resonance imaging potentially acting as a marker of inflammatory status. Pending clinical trials, we examined the interactions of Ferumoxtran-10 with human monocyte-macrophages (HMMs) in vitro to assess its safety and lack of pro-inflammatory activity. After 72 h, Ferumoxtran-10 was not toxic at 1 mg/ml and may be only mildly toxic at 10 mg/ml. Viability in cells with a high intracellular Ferumoxtran-10 load was not affected over 14 days. Ferumoxtran-10 did not interfere with baseline or stimulated cytokine (interleukin-12, interleukin-6, tumour necrosis factor- α or interleukin-1 β) or superoxide anion production or with Fc-receptor-mediated phagocytosis. Similarly, Ferumoxtran-10 did not induce cytokine production and was not chemotactic. High-resolution electron microscopy and selected-area electron diffraction confirmed the core of Ferumoxtran-10 is composed of crystalline magnetite. Bright field transmission electron microscopy of thin sections demonstrated that Ferumoxtran-10 was retained in lysosomes of HMM for several days. Ferumoxtran-10 is not toxic to HMMs in vitro, does not activate them to produce pro-inflammatory cytokines or superoxide anions, is not chemotactic and does not interfere with Fc-receptor-mediated phagocytosis. Furthermore, extremely high intracellular Ferumoxtran-10 concentrations had only slight or no effects on these key activities.