Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis.

OBJECTIVE: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. METHOD: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. RESULTS: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1ß and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). CONCLUSIONS: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.

Applying reverse stable isotope labeling analysis by mid-infrared laser spectroscopy to monitor BDOC in recycled wastewater.

Biological stability of treated wastewater is currently determined by methods such as biological oxygen demand, ATP-quantification, or flow-cytometric cell counting. However, the continuous increase in water reclamation for wastewater reuse requires new methods for quantifying degradation of biodegradable dissolved organic carbon (BDOC) ranging from very small to high concentrations of dissolved organic carbon (DOC). Furthermore, direct activity measures or absolute concentrations of BDOC are needed that produce comparable and reproducible results in all laboratories. Measuring carbon mineralization by CO2 evolution presents a suitable approach for directly measuring the microbial degradation activity. In this work, we investigated the extent of BDOC in water samples from effluent of a wastewater treatment plant and after purification by ultrafiltration over 204 days. BDOC monitoring was performed with the recently introduced reverse stable isotope labeling (RIL) analysis using mid-infrared spectroscopy for the monitoring of microbial CO2 production. Average BDOC degradation rates ranged from 0.11 to 0.32 mg L-1 d-1 for wastewater treatment plant effluent and from 0.03 to 0.22 mg L-1 d-1 after ultrafiltration. BDOC was degraded over >90 days indicating the long-term instability of the DOC. Degradation experiments over 88 days revealed first order kinetic rate constants for BDOC which corresponded to 12.7 ·â€¯10-3 d-1 for wastewater treatment plant effluent and 2.7 ·â€¯10-3 d-1 after ultrafiltration, respectively. A thorough sensitivity analysis of the RIL showed that the method is very accurate and sensitive with method detection limits down to 10 µg·â€¯L-1 of measured CO2.

The monogenean Paradiplozoon ichthyoxanthon behaves like a micropredator on two of its hosts, as indicated by stable isotopes.

The analysis of stable isotopes of carbon and nitrogen has been used as a fingerprint for understanding the trophic interactions of organisms. Most of these studies have been applied to free-living organisms, while parasites have largely been neglected. Studies dealing with parasites so far have assessed the carbon and nitrogen signatures in endoparasites or ectoparasites of different hosts, without showing general trends concerning the nutritional relationships within host-parasite associations. Moreover, in most cases such systems involved a single host and parasite species. The present study is therefore the first to detail the trophic interactions of a freshwater monogenean-host model using δ13C and δ15N, where a single monogenean species infects two distinctly different hosts. Host fishes, Labeobarbus aeneus and Labeobarbus kimberleyensis from the Vaal Dam, South Africa, were assessed for the monogenean parasite Paradiplozoon ichthyoxanthon, individuals of which were removed from the gills of the hosts. The parasites and host muscle samples were analysed for signatures of δ13C and δ15N using an elemental analyser connected to an isotope ratio mass spectrometer. Host fish appear to use partly different food sources, with L. aeneus having slightly elevated δ13C signatures compared to L. kimberleyensis, and showed only small differences with regard to their nitrogen signatures, suggesting that both species range on the same trophic level. Carbon and nitrogen signatures in P. ichthyoxanthon showed that the parasites mirrored the small differences in dietary carbon sources of the host but, according to δ15N signatures, the parasite ranged on a higher trophic level than the hosts. This relationship resembles predator-prey relationships and therefore suggests that P. ichthyoxanthon might act as a micropredator, similar to blood-sucking arthropods such as mites and fleas.

Assessing the treatment costs and the fertilizing value of the output products in digestate treatment systems.

The objective of this paper was to advance towards finding sustainable solutions to deal with biogas digestate and contribute to faster development of the market for digestate treatment products. The study compares digestate treatment costs through four different treatment plants, estimates the potential fertilizing and humus value (PFHV) of the derived products and allocates the cash flows to show the possible regional benefits. The treatment costs for the pre-dried solid fraction of digestate ranged from €19 to €23/tonne output. These costs may be covered by vending treatment products at a price reaching at least 34-41% of their PFHV (ca €55/tonne). Treatment of raw digestate generates high operating costs (€216-247/tonne output), much higher than the PFHV of the products (ca €35-51/tonne). For such systems either the treatment has to be financially subsidized by the authorities or €13-32/tonne input should be covered by the substrate deliverers as a disposal fee. Nevertheless, a well-prepared investment concept in this field may allow the local binding of up to 80% of total cash flows. Finally, the current difficult market situation of the treatment products can be primarily improved by clearing their legal status at European level.

[Social inequality and participation in aging urban societies]. / Soziale Ungleichheit und Partizipation in alternden Stadtgesellschaften.

The social and political participation of elderly people is characterized by social inequality. Participation processes normally consolidate and intensify the exclusion of senior citizens having low incomes and low educational qualifications. In the research and development project "Quality of Life of Elderly People in Living Quarters" being conducted by Dortmund University of Applied Sciences and Arts, one of the questions being examined is whether and to what extent socially disadvantaged elderly people in a social space typical of the Ruhr region (reference area Gelsenkirchen-Schalke) can be included in the shaping of their quarter. This paper is based on the results of a quantitative, written survey (cross-section) on the subjects of quality of life and participation, and on a trend analysis measuring the effects of participation processes initiated on the elderly persons involved. The results of the study show that it is possible to involve socially disadvantaged elderly people in participation processes geared to the specific social space. They also indicate that elderly people from different income groups increase their social capital in the context of enabling structures.

[Theses on critical gerontology from a social science point of view]. / Thesen zur kritischen Gerontologie aus sozialwissenschaftlicher Sicht.

This contribution formulates several key statements concerning a critical gerontology and is intended as a starting point for further thought and discussion from the perspective of critical social sciences. In terms of scientific theory, it follows a concept of normative universalism, distinguishing itself from a mere "science of order", which would be restricted to social self-observation. The assumptions focus on dealing with the social construct of age(ing) under the conditions of modern capitalist societies and on putting age(ing) into context with neo-liberal economic and social politics. This contribution explains some aspects of restructuring the German welfare state into an "activating state", a process accompanied by the casualisation of many older people's life circumstances. Moreover, some cultural perspectives of self-determined life in old age are demonstrated, which invariably should also be seen as a learning task. In this way, the complex interactions between gerontology and social and political practice in terms of praxeological and critical research are covered in their totality. At the same time, critical gerontology is oriented towards what is humanly possible and attempts to identify restrictions to a fulfilling life in old age and to suggest perspectives of how such restrictions can be overcome. The aim is to reflect on our own professional behaviour, to make it more compatible theoretically with critical scientific discourses on ageing and thus contribute to the emancipation of older people from discourses of dominance.

The Asp299Gly Toll-like receptor 4 polymorphism in advanced aortic atherosclerosis.

BACKGROUND: Recently, the common Asp299Gly polymorphism of the Toll-like receptor 4 (TLR-4) was found to be associated with a reduced incidence of acute myocardial infarction and carotid atherosclerosis. As TLR-4 signalling is causally involved in atherogenesis, the polymorphism was postulated to impart protection from atherosclerosis. To explore a potential atheroprotective effect, we studied the association between the Asp299Gly polymorphism and atherosclerosis in hypertensive patients undergoing angiography for suspected renovascular disease. METHODS: 140 hypertensive subjects underwent intraarterial digital subtraction angiography, during which the presence of atherosclerotic lesions was assessed at the level of the abdominal aorta and renal arteries. Extensiveness of disease was classified as follows: atherosclerosis confined to the abdominal aorta, unilateral renal artery stenosis or bilateral renal artery stenosis. Subsequently, genotyping for the +896 A>G (Asp299Gly) single nucleotide polymorphism was performed in all patients. In statistical analyses 17 patients were excluded because of incomplete data (n=3) or a diagnosis of fibromuscular disease (n=14). RESULTS: 21 patients were found heterozygous for the 299Gly allele, whereas none of the subjects were 299Gly homozygous (299Gly allele frequency 7.8%). The prevalence of the 299Gly allele in atherosclerotic patients was not different from the prevalence observed in subjects without atherosclerotic lesions (16.9 vs 15.5%, p=0.83). Moreover, 299Gly carriership was not associated with the extensiveness of (advanced) aortic atherosclerosis (p=0.64). CONCLUSION: Our results suggest that the Asp299Gly TLR-4 receptor polymorphism is not associated with the prevalence nor extensiveness of (advanced) aortic atherosclerosis.

A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995.

BACKGROUND: The quality of information gathered from homeopathic pathogenetic trials (HPTs), also known as 'provings', is fundamental to homeopathy. We systematically reviewed HPTs published in six languages (English, German, Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality in terms of the validity of the information they provide. METHODS: The literature was comprehensively searched, only published reports of HPTs were included. Information was extracted by two reviewers per trial using a form with 87 items. Information on: medicines, volunteers, ethical aspects, blinding, randomization, use of placebo, adverse effects, assessments, presentation of data and number of claimed findings were recorded. Methodological quality was assessed by an index including indicators of internal and external validity, personal judgement and comments of reviewers for each study. RESULTS: 156 HPTs on 143 medicines, involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per volunteer). There was wide variation in methods and results. Sample size (median 15, range 1-103) and trial duration (mean 34 days) were very variable. Most studies had design flaws, particularly absence of proper randomization, blinding, placebo control and criteria for analysis of outcomes. Mean methodological score was 5.6 (range 4-16). More symptoms were reported from HPTs of poor quality than from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects were claimed in 98% of publications. On average about 84% of volunteers receiving active treatment developed symptoms. The quality of reports was in general poor, and much important information was not available. CONCLUSIONS: The HPTs were generally of low methodological quality. There is a high incidence of pathogenetic effects in publications and volunteers but this could be attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe. The central question of whether homeopathic medicines in high dilutions can provoke effects in healthy volunteers has not yet been definitively answered, because of methodological weaknesses of the reports. Improvement of the method and reporting of results of HPTs are required. REFERENCES: References to all included RCTs are available on-line at.

In-situ-fluorescence-probes: a useful tool for non-invasive bioprocess monitoring.

Optical sensors appear to be very promising for different applications in modern biotechnology. They offer the possibility to interface all the well known optical analysis techniques to bioprocesses via fiber optical cables. Thus, high sophisticated and sensitive optical analysis techniques can be coupled to a bioprocess via these light signal transporting fibers. A wide variety of sensor types for application in biotechnology has been described. Normally these sensors are non-invasive and the response times are nearly instantaneous. In particular, the use of glass fiber technology makes these sensors small, robust and reduces their costs.

Scale-up of dialysis fermentation for high cell density cultivation of Escherichia coli.

In dialysis fermentations inhibiting metabolites can be removed from cell suspensions resulting in a prolonged exponential growth phase and higher production yields. Because of successful high cell density cultivations of Escherichia coli in a laboratory dialysis reactor, a scale-up of the process was investigated. To provide sufficient membrane area for dialysis in a technical scale fermenter, an external membrane module was used, that was also applied for oxygen supply to the culture in the external loop. Cultivations with recombinant E. coli K12, with and without induction, in 2- and 300-l reactors were carried out using external modules. Cell densities exceeding 190 g l(-1), previously obtained in laboratory dialysis fermentation, were also produced with external dialysis modules. Protein concentration in a 300-l reactor was increased to the 3.8-fold of industrial fed-batch-fermentations.

Cost effectiveness of eptifibatide in acute coronary syndromes; an economic analysis of Western European patients enrolled in the PURSUIT trial. The Platelet IIa/IIb in unstable Angina: Receptor Suppression Using Integrilin Therapy.

AIMS: To assess the direct medical costs and cost effectiveness of routine eptifibatide use amongst patients with unstable angina and myocardial infarction without persistent ST-segment elevation in the Western European subgroup of the PURSUIT trial. METHODS AND RESULTS: Health care resources were collected for the Western European PURSUIT trial patients (n=3697). Unit costs for major resources were developed within six countries using a consistent bottom-up methodology. Resource consumption from the Western European population was used to calculate the average direct medical costs per patient in the eptifibatide and placebo arms of the trial. Eptifibatide was estimated to cost 524 Euros per treatment. Long-term survival estimated from the 6-month trial survival data and combined with the cost data was used to calculate cost-effectiveness ratios. Additionally, cost per death and non-fatal myocardial infarction at 30 days was calculated. Sensitivity analyses were conducted on the discount rate and resource consumption. Cost-effectiveness ratios ranged from 9603 Euros to 18 115 Euros per year of life saved with 3% discount. Using resource consumption based on countries with low coronary arteriography rates, the cost per year of life saved was between 3329 Euros and 10 079 Euros. Using resource consumption based on high coronary arteriography rate countries, the cost per year of life saved was between 17 089 Euros and 24 099 Euros. Assuming no difference in treatment costs except for the addition of eptifibatide, the incremental cost per year of life saved was 23 818 Euros. CONCLUSIONS: Routine eptifibatide use was associated with a reduction in the combined end-point of death and myocardial infarction at 30 days, which was sustained at 6 months. Long-term projections indicate a modest increase in survival in eptifibatide patients. These data translate into cost-effectiveness ratios that compare favourably with other new technologies that are currently in use.

Metabolic effects of HAY's diet.

The aim of the study was, to evaluate the metabolic effect of HAY's diet on protein turnover, fat oxidation, respiratory quotient, body fat and weight loss. Twelve healthy adults received an individually regular diet and thereafter a corresponding isocaloric and isonitrogenous 10-day HAY-diet. Protein turnover and 13C-fat oxidation were investigated after administration of [15N]glycine and an [U-13C]algae lipid mixture. The 15N and 13C enrichment in urine and breath were measured by isotope ratio mass spectrometry. The respiratory quotient was measured by indirect calorimetry. Body fat, total body water and lean body mass were estimated by bio-electric impedance analysis. HAY's diet led to a significantly higher 13C-fat oxidation (15.4 vs. 22.0% P < 0.01), corresponding to a lower respiratory quotient (0.88 vs. 0.81; P < 0.01), whereas the protein turnover remained constant in both diets (3.06 vs. 3.05 g/kg/day). HAY's diet did not reduce total body water, lean body mass, body fat and body weight (72.2 vs. 71.4 kg).

Interpretation of renal angiography by radiologists.

OBJECTIVE: Different radiologists may show considerable variation in their interpretation of renal angiograms. We therefore wished to establish the reliability of their interpretation. DESIGN: Assessment of the intra- and inter-observer agreement of the interpretation of renal angiograms. SETTING: Tertiary referral university hospital. PATIENTS: Hypertensive patients suspected of renovascular hypertension on clinical grounds or on the basis of renography. INTERVENTIONS: Patients were prospectively selected to undergo a renal angiography via the femoral approach. MAIN OUTCOME MEASURES: Intra- and inter-observer agreement of the degree and site of stenosis. RESULTS: The difference between two estimates of the degree of stenosis ranged from 0 to 65% for the individual readers and from 0 to 75% between two readers. When the site of greatest stenosis was in the origin of the renal artery, the intra-observer agreement kappa ranged from 0.54-0.71, the inter-observer agreement across multiple readers being 0.43. In a post hoc analysis using two different cut-off points of stenosis (50 or 70%), the intra- and inter-observer agreement was better at the 70% cut-off-point. In a subset of patients with stenosis and a renin ratio greater than 1.5, both the intra- and inter-observer agreement were much better than when all angiograms were considered. CONCLUSIONS: Assessment of the diagnostic performance of three experienced radiologists in their interpretation of renal artery angiograms indicates that the intra- and inter-observer agreement with respect to their estimates of the degree of stenosis and the site of greatest stenosis are rather poor but their diagnostic performance improves in patients with stenosis and a renin ratio greater than 1.5. There is a need for more objective assessment of renal artery lesions.

MR angiography of the iliac and upper femoral arteries using four different inflow techniques.

OBJECTIVE: The purpose of this study was to compare two inflow MR angiography pulse sequences obtained with and without systolic synchronization. We also compared these two MR angiography pulse sequences with conventional angiography. SUBJECTS AND METHODS: Thirty-one consecutive patients who were scheduled for conventional angiography because of symptomatic atherosclerotic occlusive disease of the iliac or femoral artery underwent MR angiography using four different MR angiography techniques. These techniques consisted of a multiple two-dimensional inversion prepulse gradient-recalled echo technique (turbo field-echo) obtained with and without systolic synchronization and a multiple two-dimensional gradient-recalled echo technique (fast field-echo) obtained with and without systolic synchronization. We then compared image quality and our ability to detect and grade degree and length of stenosis, using conventional angiography as the gold standard. RESULTS: The systolic-synchronized turbo field-echo sequence produced the best results both objectively and subjectively. Comparing systolic-synchronized turbo field-echo and fast field-echo techniques with conventional angiography regarding detection and grading degree of stenoses, we found no statistically significant differences. CONCLUSION: Systolic synchronization proved to be of significant importance for image quality. The systolic-synchronized turbo field-echo pulse sequence proved to be superior to the other three MR angiography techniques.

The transmission of campylobacter in piggeries; an epidemiological study.

The campylobacter infection of 10 sows and their piglets was monitored. These pigs were kept on two multiplier farms. Rectal faeces samples were taken from the sows shortly before littering and at different intervals after littering. Swab samples of rectal content were taken from six piglets per sow at different intervals after birth. Nine sows were shown to be infected with campylobacter before litter and all sows after litter, with an average colony count of 4.1 in log N g-1 of faeces. Half of the piglets became infected with campylobacter during the first week of life and 85%, after four weeks. Two genetic subtyping methods (ERIC-PCR and RFLP) were used to study the relationships between campylobacter isolates from sows and piglets. A large diversity of campylobacter subtypes was found. Nevertheless, piglets and their mothers often harboured campylobacter isolates with identical genetic subtyping profiles, suggesting that piglets become infected via their mothers. However, observed similarities in genetic subtyping profiles between campylobacters isolated on different farms made this difficult to prove.

Renovascular disease in patients with hypertension: detection with systolic and diastolic gating in three-dimensional, phase-contrast MR angiography.

PURPOSE: To evaluate the usefulness of three-dimensional, phase-contrast magnetic resonance (MR) angiography performed with cardiac synchronization in the assessment of renal arteries. MATERIALS AND METHODS: Thirty-eight patients (24 men, 14 women) underwent three-dimensional, phase-contrast MR angiography without gating and with systolic and diastolic gating. Conventional angiography was used as the standard of reference. RESULTS: The sensitivity for the detection of all stenoses (> 0%) was 93% with systolic, 92% with diastolic, and 77% without gating. However, there was no difference between the three techniques in the diagnosis of hemodynamically significant stenoses (> 50%). The mean arterial length depicted was significantly better with diastolic gating than with either of the other techniques (P < .0001). Vascular disease was significantly overestimated with systolic gating relative to estimation without (P = .030) or with diastolic (P = .008) gating. CONCLUSION: Three-dimensional, phase-contrast MR angiography provides good image quality and enables assessment of renovascular disease. Cardiac gating has limited improvement of these results.

Investigation of an outbreak of Campylobacter upsaliensis in day care centers in Brussels: analysis of relationships among isolates by phenotypic and genotypic typing methods.

An outbreak of Campylobacter upsaliensis in four Brussels day care centers (A, B-1, B-2, and C) affected 44 children. Diarrhea was the major symptom. From January 1991 to June 1992, the outbreak strain was isolated from 3, 1, and 21 (of 68) children in centers A, B-1, and B-2, respectively, and from 19 of 22 children in center C, IgG, IgM, and IgA antibodies were detected by Western blotting of serum specimens of 9 of 10 and 13 of 16 children in centers B-2 and C, respectively. Strains were typed by biotyping, DNA restriction-based and antibiotic susceptibility typing, whole cell protein and plasmid analysis, restriction fragment length polymorphism (RFLP), and polymerase chain reaction (PCR). On the basis of RFLP and PCR typing, the strains could be divided into two strongly related clonal variants: One was isolated only from the children of center A and the second only from children in the other day care centers.

Hydrogen breath test as a simple noninvasive method for evaluation of carbohydrate malabsorption during exercise.

The aim of this study was to examine hydrogen (H2) production with the hydrogen breath test (HBT) after ingesting primarily digestible carbohydrate (CHO) during 3 h of 75% maximal oxygen consumption exercise. This was done to indicate CHO overflow in the colon which may occur when gastric emptying, intestinal transit and CHO absorption are not matched and CHO accumulates in the colon where it is subject to bacterial degradation. Further, this study was designed to assess breath H2 production as a function of the type of CHO ingested and the type of exercise. A group of 32 male triathletes performed three exercise trials at 1-week intervals with either a semisolid (S) intake, an equal energy fluid intake (F) or a fluid placebo (P). Each trial consisted of cycling (sessions 1 and 3) and running (sessions 2 and 4). The mixed-expired H2 concentrations in the resting and "recovery" periods (5 min after each session) did not change significantly in time and did not differ among intakes. There were also no significant differences in H2 concentrations between resting and "recovery" conditions. During exercise, H2 concentrations decreased three to six-fold in comparison to resting and recovery levels and differed among intakes (ANOVA; P < 0.05). The H2 concentrations were almost continuously lower with P than with F and S. The H2 concentrations were significantly higher during running than during cycling. During exercise, we found that CHO overflow could be compared among intakes and between exercise types by using the HBT, provided the influence of other factors on H2 excretion--ventilation and intestinal blood flow--was similar for each condition.

Hepatitis A as an occupational hazard.

Few studies have been carried out to evaluate the role of hepatitis A virus (HAV) as an occupational hazard. Our analysis of data on occupational diseases in Germany showed that hepatitis A ranks as third among infectious occupational diseases. Morbidity based on the frequency of compensation (15.2%) was in the same range as that observed for hepatitis B (19.7%). In another study, data were collected on anti-HAV prevalence among 2293 hospital workers in southwest Germany. Anti-HAV prevalence of hospital staff responsible for patient care and that of the general population were comparable, while food-handlers under the age of 30 years had a higher degree of anti-HAV prevalence. When an evaluation of anti-HAV prevalence data was carried out on persons younger than 30 years who comprised subsets of the medical staff, the relative risk was: charwomen 4.2, food-handlers 2.49, and paediatric nurses 1.84, showing that they had higher prevalence rates than nurses 1.25, physicians 1.09 and laboratory assistants 0.93. Vaccinations for the prevention of hepatitis A should therefore reach individuals that have an increased occupational risk: food-handlers, health care workers in infectious diseases and paediatrics, medical staff in laboratories handling stool samples, medical charwomen and, according to previously published work, staff of day care centres and sewerage workers.