Using multi-event hydrologic and hydraulic signatures from water level sensors to diagnose locations of uncertainty in integrated urban drainage models used in living digital twins.

Digital twins of urban drainage systems require simulation models that can adequately replicate the physical system. All models have their limitations, and it is important to investigate when and where simulation results are acceptable and to communicate the level of performance transparently to end users. This paper first defines a classification of four possible 'locations of uncertainty' in integrated urban drainage models. It then develops a structured framework for identifying and diagnosing various types of errors. This framework compares model outputs with in-sewer water level observations based on hydrologic and hydraulic signatures. The approach is applied on a real case study in Odense, Denmark, with examples from three different system sites: a typical manhole, a small flushing chamber, and an internal overflow structure. This allows diagnosing different model errors ranging from issues in the underlying asset database and missing hydrologic processes to limitations in the model software implementation. Structured use of signatures is promising for continuous, iterative improvements of integrated urban drainage models. It also provides a transparent way to communicate the level of model adequacy to end users.

Evaluation of dose to cardiac structures during breast irradiation.

OBJECTIVE: Adjuvant radiotherapy for breast cancer can lead to late cardiac complications. The highest radiation doses are likely to be to the anterior portion of the heart, including the left anterior descending coronary artery (LAD). The purpose of this work was to assess the radiation doses delivered to the heart and the LAD in respiration-adapted radiotherapy of patients with left-sided breast cancer. METHODS: 24 patients referred for adjuvant radiotherapy after breast-conserving surgery for left-sided lymph node positive breast cancer were evaluated. The whole heart, the arch of the LAD and the whole LAD were contoured. The radiation doses to all three cardiac structures were evaluated. RESULTS: For 13 patients, the plans were acceptable based on the criteria set for all 3 contours. For seven patients, the volume of heart irradiated was well below the set clinical threshold whereas a high dose was still being delivered to the LAD. In 1 case, the dose to the LAD was low while 19% of the contoured heart volume received over 20 Gy. In five patients, the dose to the arch LAD was relatively low while the dose to the whole LAD was considerably higher. CONCLUSION: This study indicates that it is necessary to assess the dose delivered to the whole heart as well as to the whole LAD when investigating the acceptability of a breast irradiation treatment. Assessing the dose to only one of these structures could lead to excessive heart irradiation and thereby increased risk of cardiac complications for breast cancer radiotherapy patients.

13Carbon and 15nitrogen isotopes in autopsy liver tissue samples from Greenlandic Inuit and Danes: consumption of marine versus terrestrial food.

BACKGROUND/OBJECTIVES: The content of (13)C and (15)N isotopes is higher in marine than in terrestrial food. (13)C and (15)N in human tissue therefore reflects the relative proportions of marine and terrestrial food consumed by the individual. The objective of this study was to measure (13)C and (15)N in liver tissue from Greenlandic Inuit and Danes. SUBJECTS/METHODS: Normal liver tissue was obtained at autopsy in 1992-1994 from 60 Inuit with a median age of 61 years (range 25-83) and in 1986 from 15 ethnic Danes with a median age of 84 years (range 66-93). By sieving, liver tissue was separated in a 'cellular fraction' and a 'connective tissue fraction'. (13)C and (15)N in dry liver tissue was measured on a mass spectrometer. delta(13)C indicates the (13)C content relative to the IAEA-CH-6 reference standard. delta(15)N indicates (15)N content relative to the atmospheric nitrogen reference standard. RESULTS: Inuit: median delta(13)C was -21.2 per thousand in cellular and -20.0 per thousand in connective tissue fractions (P=0.001). Median delta(15)N was 10.6 per thousand in both cellular and connective tissue fractions. Body mass index was negatively correlated with delta(13)C in the connective tissue fraction (r(s)=-0.42, P=0.057). Danes: median delta(13)C was -27.0 per thousand in cellular and -24.3 per thousand in connective tissue fractions (P=0.11). Median delta(15)N was 9.5 per thousand in cellular and 8.9 per thousand in connective tissue fractions (P=0.5). Inuit had higher delta(13)C than Danes in both cellular and connective tissue fractions (P<0.001) as well as higher delta(15)N in the cellular fraction (P=0.01). CONCLUSIONS: Inuit showed considerable variation in the ratio between marine and terrestrial food consumption, reflecting a vanishing hunter culture where elderly Inuit still adhere to the traditional hunters food with a high content of marine food, whereas the younger urbanized Inuit population consume food with a lower content of marine food and a higher content of terrestrial food. Danes consumed food of almost exclusively terrestrial origin. The present (13)C and (15)N analyses are in accordance with the dietary patterns obtained by dietary surveys.

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians.

The purpose of the study was to test the hypothesis that single nucleotide polymorphisms (SNPs) within interleukin (IL)-18, TNF-alpha, IL-6 and IL-10 gene promoter regions are risk factors for cognitive decline in healthy octogenarians, and to isolate the strongest inflammatory biomarkers of cognitive function in the peripheral blood. The Wechsler Adult Intelligence Scale was administered to 112 individuals at ages 80 and 85. An IL-18 haplotype was an independent risk factor of poor Performance IQ. The TNF-308GA genotype was related to individual declines in Verbal IQ, and the IL-10-592 CC genotype was related to better Verbal IQ at the age of 80. Circulating levels of TNF-alpha, sTNFRs, and IL-6 were negatively correlated with IQ at age 85 and less strongly to IQ at age 80 with activation of the TNF system as the strongest biomarker. In conclusion, SNPs related to high proinflammatory or low anti-inflammatory activity are independent risk factors of reduced cognitive function in octogenarians. Only the IL-18 haplotype was associated with inflammation in the peripheral blood and only with regard to circulating TNF-alpha.

High serum YKL-40 level in a cohort of octogenarians is associated with increased risk of all-cause mortality.

YKL-40 is secreted by macrophages, neutrophils, chondrocytes, endothelial-, vascular smooth muscle- and cancer cells. Interleukin (IL)-6 stimulates YKL-40 production in human in vivo studies. High serum YKL-40 is associated with poor prognosis in patients with inflammatory diseases and cancer. We studied whether serum YKL-40 was associated with systemic low-level inflammation, an immune risk phenotype, and mortality in relatively healthy 80-year old humans. Serum YKL-40, IL-6 and tumour necrosis factor (TNF)-alpha were measured by enzyme-linked immunosorbent assays (ELISAs) in octogenarians (n = 151) and serum YKL-40 in 18-30-year-olds (n = 89). Fifty-one of the octogenarians died during the 6-year follow-up. Serum YKL-40 in octogenarians was higher compared to the level in young people (median 116 versus 31 microg/l, P < 0.0005). Serum YKL-40 correlated with serum IL-6 in elderly women (Spearman's rho = 0.30, P = 0.009) and men (rho = 0.25, P = 0.003), but only with serum TNF-alpha (rho = 0.23, P = 0.05) and C-reactive protein (CRP) (rho = 0.57, P < 0.0005) among the elderly women. In addition, high serum level of YKL-40 was associated with a low CD4 : CD8 cell ratio. Univariate analysis of serum YKL-40 (logarithmically transformed and divided by tertiles) showed significant association with all-cause mortality [tertile 3: hazard ratio (HR) = 2.38, 95% confidence interval (CI): 1.19-4.78, P = 0.02]. The effect persisted after adjusting for potential confounders (sex, smoking, body mass index, chronic disease and anti-inflammatory medicine). These results suggest that serum YKL-40 is a prognostic and sensitive biomarker of all-cause mortality in octogenarians.

Immunoassays of urokinase (uPA) and its type-1 inhibitor (PAI-1) in detergent extracts of breast cancer tissue.

Two immunoassays for quantitation of the biological markers uPA and PAI-1 were evaluated for their use with detergent extracts of breast cancer tissue. Both assays were based on murine monoclonal capture antibodies and rabbit polyclonal detector antibodies. Horseradish peroxidase-conjugated goat anti-rabbit antibodies enabled measurement of the bound antigen. The detection limit of the uPA assay was 13 pg/ml, with a linear dose-response relationship up to 350 pg/ml. The assay detected free uPA as well as uPA in complex with PAI-1 and/or with its receptor. The detection limit of the PAI-1 assay was 50 pg/ml, with a linear dose-response relationship up to 1500 pg/ml. The assay detected both free PAI-1 and uPA:PAI-1 complex. Both assays were validated for detergent extracts using immunoabsorption and recovery tests. Highly significant associations between tumour tissue uPA and PAI-1 levels and prognosis were verified in a cohort of 164 lymph node-negative primary breast cancer patients. It is concluded that the two immunoassays are well-suited for the quantitation of uPA and PAI-1 in detergent extracts of breast cancer tissues.

Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people.

Ageing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-alpha) initiates the inflammatory cascade and has been linked to several age-associated disorders. It remains, however, unknown if TNF-alpha is associated with mortality in old populations. The aim of the present study was to investigate if serum levels of TNF-alpha were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF-alpha and IL-6 on survival in the following 6 years. A total of 133 participants died during this follow-up period. TNF-alpha was associated with mortality in men, but not in women, whereas low-grade elevations in IL-6 were associated strongly with mortality in both sexes. TNF-alpha explained only 7% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate that at least in old populations chronic elevated levels of TNF-alpha and IL-6 have different biological functions that trigger age-associated pathology and cause mortality.

Para-aminobenzoic acid (PABA) used as a marker for completeness of 24 hour urine: effects of age and dosage scheduling.

OBJECTIVE: To examine the age dependency of the urinary para-aminobenzoic acid (PABA) excretion, and if a delayed PABA excretion can be overcome by advancing intake schedule; and to examine the recovery of PABA in fractionated urinary samples collected during 24 h after single and repeated doses of PABA. DESIGN: Cross-over study with subjects randomized to start with recommended schedule of PABA administration (80 mg at 08:00, 12:00 and 18:00; PABA18) and then an advanced schedule (80 mg at 08:00, 12:00 and 15:00; PABA15) or vice versa. One subgroup of eight subjects collected individual urine specimens for 24 h after a morning dose of 80 mg of PABA, and another subgroup of 10 subjects collected individual urine specimens for 24 h after ingestion of 80 mg of PABA three times at mealtimes. SUBJECTS: Employees and relatives from the Danish Food Administration. SETTING: Ninety-nine healthy volunteers (61 females and 38 males) aged 30-91 y. RESULTS: Linear regressions for PABA15 and PABA18 demonstrate significantly less recovery with age (PABA15: r(2)=0.1784, P=0.0002; PABA18: r(2)=0.1273, P=0.0019). Linear regression of DeltaPABA (PABA15-PABA18) with age showed the best fit line to be horizontal (slope -0.0066, P=0.89; 95% CI -0.1046, 0.0915) and with a Y-intercept not significantly different from 0 (1.575; 95% CI -4.176, 7.326). In this population the lower limit for complete 24 h urine collection was 79.2%. After a single dosage of 80 mg PABA 70-85% was recovered after 8 h. Within 16 h after ingestion of 240 mg PABA at recommended hours the lowest acceptable recovery (78.1%) was reached. CONCLUSION: There is a gradual decline of PABA recovery with age that cannot be overcome by advancing the dosage schedule. Because of a lower delimiting PABA recovery for the elderly, some 24 h collections in this age group will be rejected unjustly (false-negatives). Also, with the currently recommended dosage schedule (PABA taken with the main meals) the risk of false-positive 24 h urine collections prevails. With refinement of the PABA test procedure, ie employing a specific analytical method and age-dependent cut-off values, the test may achieve a higher specificity and sensitivity.

Body composition of 80-years old men and women and its relation to muscle strength, physical activity and functional ability.

OBJECTIVE: To measure body composition and analyse the relation to muscle strength, physical activity and functional ability in healthy, old subjects, and to relate the results to an optimal BMI level for the elderly. SETTING: Subjects aged 80 years living at home from the 1914-population in Glostrup, Denmark. SUBJECTS AND METHOD: 121 men and 113 women had their height and weight measured. Body fat mass and fat-free mass were assessed by bioelectrical impedance. Muscle strength was measured as handgrip, elbow flexion, knee extension, body flexion and body extension. Physical activity was self reported and functional ability was assessed by the Physical Performance Test (PPT) and self reported mobility including information about tiredness and help. RESULTS: After dividing BMI into three groups: BMI < 24, BMI 24-29 and BMI > 29 no relationship was seen between a BMI interval of 24-29 kg/m2, and physical activity and functional ability. BMI was related to body fat mass, and FFM was related to muscle strength. Muscle strength was related to mobility and PPT. Mobility and PPT were mutually related and were related to physical activity. CONCLUSION: Our cross sectional study did not support newly proposed guidelines for the elderly of an optimal BMI interval of 24-29 kg/m2. We found relations between body composition, muscle strength, physical activity and functional ability.

Is ageing associated with a shift in the balance between Type 1 and Type 2 cytokines in humans?

The balance between Type 1 and Type 2 cytokines is important for the outcome of several infectious diseases. As elderly humans show increased morbidity and mortality from infectious diseases, this study tests if ageing is associated with a change towards Type 2 dominance in T cells. Expression of IFN-gamma, and IL-4 was measured in CD4+ and CD8+ T cells by flow cytometry in three groups: young controls (n=28), 81-year-olds (n=22), and centenarians (n=25). The major findings were that the percentage of IFN-gamma+ as well as IL-4+ T cells was increased in aged subjects. Furthermore, after adjusting for decreased lymphocyte counts in the elderly, the concentration in the blood of IFN-gamma+ and IL-4+ CD8+ T cells was still increased in the 81-year-olds. In centenarians, a shift towards a relative dominance of Type 2 cytokine expression was found within CD8+ T cells. Furthermore, the percentage of T cells with cytokine expression was closely correlated to the in vivo expression of CD95 and CD45RO. In conclusion, we found some evidence for an age-related shift towards a Type 2 cytokine profile.

Assessment of habitual energy and macronutrient intake in adults: comparison of a seven day food record with a dietary history interview.

OBJECTIVE: To examine the quantitative agreement between a 7 day food record and a diet history interview when these are conducted under the same conditions and to evaluate whether the two methods assess habitual diet intake differently among subgroups of age and body mass index (BMI). DESIGN: Cross-sectional study. SETTING: Population study, Denmark. SUBJECTS: A total of 175 men and 173 women aged 30-60 y, selected randomly from a larger population sample of Danish adults. INTERVENTIONS: All subjects had habitual diet intake assessed by a diet history interview and completed a 7 day food record within 3 weeks following the interview. The diet history interview and coding of records were performed by the same trained dietician. MAIN OUTCOME MEASURE: Median between-method difference in assessment of total energy intake, absolute intake of macronutrients, and nutrient energy percentages. Difference between reported energy intake from both methods and estimated energy expenditure in different subgroups. RESULTS: Energy and macronutrient intake was assessed slightly higher by the 7 day food record than by the diet history interview, but in absolute terms the differences were negligible. The between-method difference in assessment of total energy intake appeared to be stable over the range of age and BMI in both sexes. As compared to estimated total energy expenditure, both diet assessment methods underestimated energy intake by approximately 20%. For both methods the under-reporting increased by BMI in both sexes and by age in men. CONCLUSIONS: Energy and macronutrient intake data collected under even conditions by either a 7 day food record or a diet history interview may be collapsed and analysed independent of the underlying diet method. Both diet methods, however, appear to underestimate energy intake dependent on age and BMI. SPONSORSHIP: Danish Medical Research Council, the FREJA programme.

Decreased natural killer cell activity is associated with atherosclerosis in elderly humans.

Well-preserved natural killer cell (NK) activity has been associated with successful aging. The aim of the present study was to perform detailed analyses of NK cell function and to investigate the clinical significance of the NK cell number and function in relationship to health in a large cohort of elderly humans. It was tested if the potential of natural cytotoxicity in the blood (evaluated as an index including cytotoxicity per NK cell and the number of circulating NK cells) was preserved in 174 81-year-old humans versus 91 young controls and if NK cell mediated immunity was associated with age-related inflammatory diseases such as atherosclerosis. Elderly people had decreased cytotoxicity per NK cell in short-term but not in long-term assays. Ca(2+) independent cytotoxicity was unaltered, and NK cells maintained their cytotoxic responses to interleukin-2 and interferon-alpha signals. The decreased cytotoxicity per NK cell was not completely counteracted by increased circulating numbers of NK cells in the blood. Elderly people with severe medical disorders had low numbers of circulating NK cells. Furthermore, elderly people with atherosclerosis had low cytotoxicity per NK cell and a high number of circulating neutrophils.

Quality control including validation in dietary surveys of elderly subjects. The validation of a dietary history method (the SENECA-method) used in the 1914-population study in Glostrup of Danish men and women aged 80 years.

BACKGROUND: Quality control including validation in dietary surveys is needed to reduce and detect errors which would lead to an attenuated scientific foundation for the diet-disease relationship. Especially studies in the elderly are needed because of limited knowledge of reference values, cut-off values etc. OBJECTIVE: To validate a modified dietary history method (the SENECA-method) in elderly subjects. DESIGN: A survey of Danish men and women aged 80 years, who participated in the 1914-population study in Glostrup. SUBJECTS AND METHOD: A pilot study (n = 34) validated the dietary history against 24-h urine collections; a main study (n = 240) compared dietary history with a 3-day estimated food record. RESULTS: Protein intake from dietary history was 10% higher than calculated protein intake from 24-h urine collections. Differences in intakes of energy and macronutrients between dietary history and 3-day food record were generally small and non-significant, and there was good agreement between the methods in classifying nutrient intakes into same tertiles. A Bland & Altman plot indicated increasing differences in energy intake between methods with increased energy intake. Evidence for under-reporting of energy intake and/or over-reporting of the physical activity level was further made plausible when physical activity ratio was compared to recognized cut-off limits. CONCLUSIONS: The modified dietary history method can be used to estimate dietary intake in 80 year old subjects, but some degree of misreporting, especially under-reporting, appears to be present. Keeping this in mind it is, however, possible to analyse dietary intake against other survey data.

TNF-alpha, leptin, and lymphocyte function in human aging.

Aging is associated with increased inflammatory activity and concomitant decreased T cell mediated immune responses. Leptin may provide a link between inflammation and T cell function in aging. The aim of the study was to investigate if plasma levels of tumor necrosis factor (TNF)-alpha were associated with leptin, circulating interleukin-2 receptors (sIL-2R), and phytohaemagglutinin (PHA) induced IL-2 production in whole blood in elderly humans. Circulating levels of TNF-alpha and sIL-2R were higher in elderly humans (N=42) compared to a young control group (N=37) whereas there was no difference with regard to IL-2 production. Furthermore, there were no age-related differences in serum levels of leptin. However, women had higher levels than men. In the elderly people, serum levels of leptin were correlated with TNF-alpha in univariate regression analysis and in a multiple linear regression analysis adjusting for the effect of gender and body mass index. Furthermore, TNF-alpha, but not leptin, was positively correlated to sIL-2R and negatively correlated to IL-2 production. In conclusion, increased plasma levels of TNF-alpha in aging is associated with poor IL-2 production ex vivo and lymphocyte activation in vivo. These associations do not seem to involve leptin.

Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis.

Ageing is associated with increased inflammatory activity in the blood. The purpose of this study was to investigate if age-related increased plasma levels of TNF-alpha were associated with atherosclerosis in a cohort of 130 humans aged 81 years. The elderly cohort had increased circulating levels of TNF-alpha, C-reactive protein (CRP), total cholesterol (TC), low-density lipoproteins (LDL) and a low high-density lipoprotein (HDL)/TC ratio compared with a young control group (n = 44). The elderly cohort was divided by tertiles into three subgroups with low, intermediate, and high levels of TNF-alpha, respectively. In the group with high TNF-alpha concentrations a significantly larger proportion had clinical diagnoses of atherosclerosis. Furthermore, weak correlations were found between TNF-alpha on one hand and blood concentrations of triglycerides, leucocytes, CRP and a low HDL/TC ratio on the other which are known as risk factors of atherogenesis and thromboembolic complications. No correlations were found between TNF-alpha, TC, LDL, or the body mass index. In conclusion, the present study shows that in a cohort of 81-year-old humans, high levels of TNF-alpha in the blood were associated with a high prevalence of atherosclerosis.

Loss of ELISA specificity due to biotinylation of monoclonal antibodies.

A significant degree of nonspecificity was found in ELISA determinations of soluble urokinase receptor (suPAR) in human blood plasma when biotinylated monoclonal antibodies (Mabs) were used for the detection layer. Surface plasmon resonance studies using both nonbiotinylated and biotinylated antibodies demonstrated that biotinylation reduced specific binding of the antibodies to their target antigen, suPAR. Furthermore, biotinylation produced a new interaction with unknown human plasma protein(s), unrelated to suPAR. Nonspecific interaction with plasma protein(s) was also observed after biotinylation of a Mab having no specific target antigen in human plasma and, in both cases, the level of nonspecific interaction was directly related to the degree of antibody biotinylation. These results reinforce earlier observations that biotinylation of antibodies can reduce the affinity of antibodies, but also indicate that, in addition, biotinylation can reduce the specificity of immunoassays for plasma proteins.

Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production.

Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year-old humans and in 91 young controls. Decreased proliferation was associated with a reduced number of true naive CD4+ cells (CD62L+CD45RO-). Furthermore, a low IL-2-stimulated proliferation was correlated with a decreased PHA response in the elderly cohort, whereas reciprocal interactions of IL-10- and IL-2-producing cells were of importance in both elderly and young subjects. Accordingly, a minimum of true naive CD4+ cells was required for a normal proliferative response to PHA, perhaps by providing sufficient IL-2 which is critical for growth of naive as well as memory cells.

The complex between urokinase and its type-1 inhibitor in primary breast cancer: relation to survival.

We examined the relationship between tumor tissue level of the complex formed of urokinase (uPA) and its type-1 inhibitor (PAI-1) and survival of breast cancer patients. The study included 342 axillary lymph node-negative and -positive primary breast cancer patients with a median follow-up of 67 months. Using a newly established ELISA, the levels of preformed uPA-PAI-1 complex were measured in tumor tissue extracts and analyzed with respect to total uPA, total PAI-1, and clinicopathological parameters, including survival. uPA-PAI-1 complex comprised a minor, variable fraction of both total uPA and PAI-1 levels. The complex levels were higher in node-negative tumors than in node-positive tumors and higher in small and low-grade tumors (all, P < or = 0.002). The tumor levels of complex, uPA, and PAI-1 were all associated with survival; high complex levels predicted longer recurrence-free survival (P = 0.03) and overall survival [OS (P = 0.005)], whereas high uPA or PAI-1 levels significantly predicted shorter survival. In multivariate Cox analysis, the only parameters that independently predicted survival were total PAI-1 level and lymph node status for recurrence-free survival and OS and, additionally, steroid hormone receptor status and grade for OS. This is the first demonstration of a relationship between uPA.PAI-1 complex tumor level and patient survival. However, total PAI-1 level showed superior prognostic power. Additional studies are needed to understand the relationship of these parameters to cancer biology and to assess the clinical utility of the uPA PAI-1 complex.

Impaired production of proinflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in elderly humans.

Ageing is associated with decreased resistance to bacterial infections and concomitant increased circulating levels of inflammatory cytokines. The purpose of the present study was to research age-related changes in levels of early mediators of the acute-phase response in whole blood supernatants following LPS stimulation, representing an ex vivo model of sepsis. Levels of tumour necrosis factor-alpha (TNF-alpha), IL-1beta and IL-6 in whole blood supernatants were measured after in vitro LPS stimulation for 24 h in 168 elderly humans aged 81 years from the 1914 cohort in Glostrup, Denmark and in 91 young controls aged 19-31 years. Levels of TNF-alpha and IL-1beta were significantly lower in elderly humans compared with young controls, whereas no difference was detected with regard to IL-6. Elderly humans with low body mass index had the lowest levels of IL-1beta. Young women had lower levels of proinflammatory cytokines compared with young men, but this difference was blurred by ageing. No relation was found between circulating plasma levels of TNF-alpha and levels after in vitro LPS stimulation. In conclusion, decreased production of TNF-alpha and IL-1beta after exposure to LPS may reflect impaired host defence against infections in the elderly and be of importance in elderly humans with underlying health disorders. However, the clinical relevance is questionable in healthy elderly people because decreased levels were found compared with young men but not compared with young women.

Prestorage leukofiltration of whole blood and SAGM blood prevents extracellular bioactive substance accumulation.

OBJECTIVES: Potentially harmful leukocyte- and platelet-derived bioactive substances are accumulated extracellularly during storage of different blood products. Therefore, we studied the effect of prestorage leukocyte filtration on concentrations of bioactive substances in whole blood (WB) and saline-adenine-glucose-mannitol (SAGM) erythrocyte suspension during storage. METHODS: Ten units of WB and 10 units of SAGM blood from 20 blood donors were stored at + 4 degrees C for 24 h. Subsequently, half of every unit was leukocyte-reduced by filtration. The 40 half units (20 filtered and 20 unfiltered) were stored at + 4 degrees C for further 34 days. Samples were collected from all 40 half blood units on day 1, 21 and 35. Total content and extracellular concentration of myeloperoxidase (MPO), eosinophil cationic protein (ECP), histamine and plasminogen activator inhibitor-1 (PAI-1) was analysed by ELISA or RIA methods. RESULTS: In unfiltered WB, the total content of all 4 substances decreased during storage, and extracellular concentrations increased significantly and storage time dependently. Similarly, this was also seen with MPO and ECP in unfiltered SAGM blood. Prestorage filtration of WB resulted in a significant reduction of total content and of extracellular concentrations of all 4 substances as well. Additionally, storage time dependent extracellular accumulation was prevented for all substances. Prestorage filtration of SAGM blood significantly reduced total content and extracellular concentrations of MPO and ECP and prevented storage time dependent extracellular accumulation. Filtered SAGM blood contained significantly lower concentrations of all analysed substances compared to filtered WB. CONCLUSION: Prestorage leukocyte filtration reduces total content of leukocyte- and platelet-derived bioactive substances and prevents the storage time dependent extracellular accumulation of these substances in WB and the partly accumulation in SAGM blood.