Mild aseptic lymphocyte-dominated vasculitis-associated lesion (ALVAL)-type reactions also present in patients with failed knee prostheses.

Aims: Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium. Methods: Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia. Results: Median metal concentrations were as follows: cobalt: 0.69 µg/g (interquartile range (IQR) 0.10 to 6.10); chromium: 1.1 µg/g (IQR 0.27 to 4.10); and titanium: 1.6 µg/g (IQR 0.90 to 4.07). Moderate ALVAL scores were found in 30% (n = 39) of the revised knees. There were ten patients with an ALVAL score of 6 or more who were revised for suspected periprosthetic joint infection (PJI), aseptic loosening, or osteolysis. R2 varied between 0.269 and 0.369 for the ordinal regression models. The most important variables were model type, indication for revision, and cobalt and chromium in the ordinal regression models. Conclusion: We found that metal particles released from the knee prosthesis can accumulate in the periprosthetic tissues. Several patients revised for suspected culture-negative PJI had features of an ALVAL reaction, which is a novel finding. Therefore, ALVAL-type reactions can also be found around knee prostheses, but they are mostly mild and less common than those found around metal-on-metal prostheses.

Scent Detection Threshold of Trained Dogs to Eucalyptus Hydrolat.

Dogs' (Canis lupus familiaris) sense of smell is based on a unique anatomy and physiology that enables them to find and differentiate low concentrations of odor molecules. This ability is exploited when dogs are trained as search, rescue, or medical detection dogs. We performed a three-part study to explore the scent detection threshold of 15 dogs to an in-house-made Eucalyptus hydrolat. Here, decreasing concentrations of the hydrolat were tested using a three-alternative forced-choice method until the first incorrect response, which defined the limit of scent detection for each tested dog. Quantitative proton nuclear magnetic resonance spectroscopy was used to identify and measure the contents of ten commercial Eucalyptus hydrolats, which are used in a dog scent training sport called "nose work". In this study, the dogs' limit of detection initially ranged from 1:104 to 1:1023 but narrowed down to 1:1017-1:1021 after a training period. The results show that, with training, dogs learn to discriminate decreasing concentrations of a target scent, and that dogs can discriminate Eucalyptus hydrolat at very low concentrations. We also detected different concentrations of eucalyptol and lower alcohols in the hydrolat products and highlight the importance of using an identical source of a scent in training a dog for participation in canine scent sport competitions and in olfactory research.

Salivary Metabolomics in the Diagnosis and Monitoring of Neurodegenerative Dementia.

Millions of people suffer with dementia worldwide. However, early diagnosis of neurodegenerative diseases/dementia (NDD) is difficult, and no specific biomarkers have been found. This study aims to review the applications of salivary metabolomics in diagnostics and the treatment monitoring of NDD A literature search of suitable studies was executed so that a total of 29 original research articles were included in the present review. Spectroscopic methods, mainly nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry, give us a broad view of changes in salivary metabolites in neurodegenerative diseases. The role of different salivary metabolites in brain function is discussed. Further studies with larger patient cohorts should be carried out to investigate the association between salivary metabolites and brain function and thus learn more about the complicated pathways in the human body.

Real-Time On-Site Multielement Analysis of Environmental Waters with a Portable X-ray Fluorescence (pXRF) System.

Strict regulations are in place to control the effluents of mining sites and other industries. Heavy metal contamination of aquatic systems caused by leakages is difficult to mitigate as it takes time to detect and localize the leak. Dynamic sampling would drastically reduce the time to locate leakages and allow faster actions to reduce the impact on the environment. The present study introduces a novel portable multielement water analysis system to simultaneously measure Mn, Ni, Cu, Zn, Pb, and U in water samples from natural sources within 15 min from the sampling. The metals are preconcentrated from a 10 mL water sample into a nanoporous filter based on bisphosphonate-modified thermally carbonized porous silicon. The metals can be conveniently analyzed from the filter with a portable XRF analyzer in field conditions. The system was empirically calibrated for a lake water matrix with neutral pH and low alkaline metal concentration. A strong correlation between the XRF intensities and the ICP-MS results was obtained in a concentration range from 50 to 10 000 µg/L. With a DPO-2000C XRF analyzer, the detection limits were 103, 86, 92, 35, 44, and 43 µg/L for Mn, Ni, Cu, Zn, Pb, and U, respectively. The corresponding values with X-MET8000 Expert Geo were 137, 46, 62, 38, 29, and 54. The system was successfully validated with simulated multielement lake water samples and piloted in field conditions. The system provides an efficient way to monitor metals in environmental waters in cases where quick on-site results are needed.

Role of Polyamine-Induced Dimerization of Antizyme in Its Cellular Functions.

The polyamines, spermine (Spm) and spermidine (Spd), are important for cell growth and function. Their homeostasis is strictly controlled, and a key downregulator of the polyamine pool is the polyamine-inducible protein, antizyme 1 (OAZ1). OAZ1 inhibits polyamine uptake and targets ornithine decarboxylase (ODC), the rate-limiting enzyme of polyamine biosynthesis, for proteasomal degradation. Here we report, for the first time, that polyamines induce dimerization of mouse recombinant full-length OAZ1, forming an (OAZ1)2-Polyamine complex. Dimerization could be modulated by functionally active C-methylated spermidine mimetics (MeSpds) by changing the position of the methyl group along the Spd backbone-2-MeSpd was a poor inducer as opposed to 1-MeSpd, 3-MeSpd, and Spd, which were good inducers. Importantly, the ability of compounds to inhibit polyamine uptake correlated with the efficiency of the (OAZ1)2-Polyamine complex formation. Thus, the (OAZ1)2-Polyamine complex may be needed to inhibit polyamine uptake. The efficiency of polyamine-induced ribosomal +1 frameshifting of OAZ1 mRNA could also be differentially modulated by MeSpds-2-MeSpd was a poor inducer of OAZ1 biosynthesis and hence a poor downregulator of ODC activity unlike the other MeSpds. These findings offer new insight into the OAZ1-mediated regulation of polyamine homeostasis and provide the chemical tools to study it.

Effect of solvent mixture pretreatment on sugar release from short-rotation coppice Salix schwerinii for biobutanol production.

This study investigated the effects of pretreatment using an acetone-butanol-ethanol (ABE) mixture with and without H2SO4 (H+) as a catalyst on sugar recovery from Salix schwerinii biomass. The sugar recovery was susceptible to both the temperature and the catalyst. Moreover, the relatively higher concentration of ABE (H+ABE4) at 200 °C yielded glucose recovery of 85.5% from the pretreated solid, higher than the recovery under other conditions. This result was mainly attributed to the compositional changes in the biomass, as the xylan and lignin were removed in large quantities by ABE pretreatment at 200 °C. Correspondingly, xylose recovery of 53.8% and glucose recovery of 12.1% were obtained from the liquid in which more sugar degradation products were formed. Ultimately, a fermentation broth containing a low concentration of ABE was successfully employed for pretreatment and showed great potential in producing fermentable sugars from S. schwerinii for biobutanol production.

Exposure to leachates from post-consumer plastic and recycled rubber causes stress responses and mortality in a copepod Limnocalanus macrurus.

Effects of household post-consumer plastics and tyre rubber on a Baltic Sea copepod Limnocalanus macrurus were assessed. Fragments of commercial recycled low-density polyethylene vegetable bags and rubber originating from recycled car tyres were incubated in seawater, and the copepods were exposed to the filtrate of the water. L. macrurus experienced erratic swimming behaviour and increased mortality in the filtrate of unwashed vegetable bags, containing elevated concentrations of alcohols, organic acids and copper. Responses of the antioxidant defence system (ADS) were recorded in copepods exposed to rubber treatments containing high concentrations of zinc. Significant responses in the ADS enzymes indicate that reactive oxygen species (ROS) formation was exceeding the detoxification capacity of the ADS which may further lead to prolonged state of oxidative stress. Observed effects of exposure on the biochemical level coincide with impaired swimming activity of the copepods, indicating possible irreversible cellular responses leading to behavioural changes and mortality.

α-Difluoromethylornithine-Induced Cytostasis is Reversed by Exogenous Polyamines, Not by Thymidine Supplementation.

Polyamine spermidine is essential for the proliferation of eukaryotic cells. Administration of polyamine biosynthesis inhibitor α-difluoromethylornithine (DFMO) induces cytostasis that occurs in two phases; the early phase which can be reversed by spermidine, spermine, and some of their analogs, and the late phase which is characterized by practically complete depletion of cellular spermidine pool. The growth of cells at the late phase can be reversed by spermidine and by very few of its analogs, including (S)-1-methylspermidine. It was reported previously (Witherspoon et al. Cancer Discovery 3(9); 1072-81, 2013) that DFMO treatment leads to depletion of cellular thymidine pools, and that exogenous thymidine supplementation partially prevents DFMO-induced cytostasis without affecting intracellular polyamine pools in HT-29, SW480, and LoVo colorectal cancer cells. Here we show that thymidine did not prevent DFMO-induced cytostasis in DU145, LNCaP, MCF7, CaCo2, BT4C, SV40MES13, HepG2, HEK293, NIH3T3, ARPE19 or HT-29 cell lines, whereas administration of functionally active mimetic of spermidine, (S)-1-methylspermidine, did. Thus, the effect of thymidine seems to be specific only for certain cell lines. We conclude that decreased polyamine levels and possibly also distorted pools of folate-dependent metabolites mediate the anti-proliferative actions of DFMO. However, polyamines are necessary and sufficient to overcome DFMO-induced cytostasis, while thymidine is generally not.

A Comparative Study of Pyrolysis Liquids by Slow Pyrolysis of Industrial Hemp Leaves, Hurds and Roots.

This study assessed the pyrolysis liquids obtained by slow pyrolysis of industrial hemp leaves, hurds, and roots. The liquids recovered between a pyrolysis temperature of 275-350 °C, at two condensation temperatures 130 °C and 70 °C, were analyzed. Aqueous and bio-oil pyrolysis liquids were produced and analyzed by proton nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and atmospheric pressure photoionization Fourier transform ion cyclotron resonance mass spectrometry (APPI FT-ICR MS). NMR revealed quantitative concentrations of the most abundant compounds in the aqueous fractions and compound groups in the oily fractions. In the aqueous fractions, the concentration range of acetic acid was 50-241 gL-1, methanol 2-30 gL-1, propanoic acid 5-20 gL-1, and 1-hydroxybutan-2-one 2 gL-1. GC-MS was used to compare the compositions of the volatile compounds and APPI FT-ICR MS was utilized to determine the most abundant higher molecular weight compounds. The different obtained pyrolysis liquids (aqueous and oily) had various volatile and nonvolatile compounds such as acetic acid, 2,6-dimethoxyphenol, 2-methoxyphenol, and cannabidiol. This study provides a detailed understanding of the chemical composition of pyrolysis liquids from different parts of the industrial hemp plant and assesses their possible economic potential.

Slow pyrolysis liquid in reducing NH3 emissions from cattle slurry - Impacts on plant growth and soil organisms.

A substantial percentage of manure nitrogen (N) can be lost as gaseous ammonia (NH3) during storage and field spreading. Lowering slurry pH is a simple and accepted method for preserving its N. Efficiency of slow pyrolysis liquid (PL) produced from birch (Betula sp.) as an acidifying agent, and its ability to reduce NH3 emissions following surface application of cattle slurry, was studied in a field experiment. Untreated slurry (US) and slurries acidified with PL and sulfuric acid (SA) were applied to the second harvest of a grass ley. Immediate NH3 emissions, grass biomass, N-yield and possible toxic impacts on soil nematodes and enchytraeids were examined. Furthermore, the effects on soil respiration, nitrogen dynamics and seed germination were studied in subsequent laboratory experiments. In the field, over one third of the water-extractable ammonium-N (NH4-N) applied was lost through NH3 volatilization from US. SA and PL acidified slurries reduced NH3-N emission rate equally from 3.4 to <0.04 kg ha-1 h-1. Acidification with SA resulted in the highest and that with PL in the lowest grass dry matter (DM) and N yield. Neither SA nor PL acidification had negative effects on soil enchytraeids or nematodes. Reduced yield production, seed germination and delayed microbial activity after PL slurry application were most probably caused by the PL containing organic compounds. However, later increase in carbon dioxide (CO2) production and improved seed germination suggest that these compounds were rapidly volatilized and/or degraded by soil microbes. Though PL efficiently cut NH3 emission from surface-spread slurry, further studies on appropriate application methods and possible phytotoxicity are needed.

Discrimination between Pancreatic Cancer, Pancreatitis and Healthy Controls Using Urinary Polyamine Panel.

BACKROUND: Polyamines play an important role in cellular proliferation, and the change in polyamine metabolism is reported in various cancers. We searched for urinary polyamine signature for distinguishing between pancreatic cancer, premalignant lesions of the pancreas (PLP), acute and chronic pancreatitis, and controls. METHODS: Patients and controls were prospectively recruited in three Finnish hospitals between October 2013 and June 2016. The patients provided a urine sample at the time of the diagnosis. The panel of 14 polyamines was obtained in a single run with mass spectrometry. The polyamine concentrations were analysed with quadratic discriminant analysis and cross-validated with leave-one-out cross-validation. RESULTS: Sixty-eight patients with pancreatic cancer, 36 with acute pancreatitis, 18 with chronic pancreatitis and 7 with PLP were recruited, as were 53 controls. The combination of 4 polyamines - acetylputrescine, diacetylspermidine, N8-acetylspermidine and diacetylputrescine - distinguished pancreatic cancer and PLP from controls (sensitivity = 94%, specificity = 68% and AUC = 0.88). The combination of diacetylspermidine, N8-acetylspermidine and diacetylspermine distinguished acute pancreatitis from controls (sensitivity = 94%, specificity = 92%, AUC = 0.98). The combination of acetylputrescine, diacetylspermidine and diacetylputrescine distinguished chronic pancreatitis from controls (sensitivity = 98%, specificity = 71%, AUC = 0.93). CONCLUSIONS: Optimally selected urinary polyamine panels discriminate between pancreatic cancer and controls, as well as between acute and chronic pancreatitis and controls.

Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase.

The biogenic polyamines, spermine, spermidine (Spd) and putrescine (Put) are present at micro-millimolar concentrations in eukaryotic and prokaryotic cells (many prokaryotes have no spermine), participating in the regulation of cellular proliferation and differentiation. In mammalian cells Put is formed exclusively from L-ornithine by ornithine decarboxylase (ODC) and many potent ODC inhibitors are known. In bacteria, plants, and fungi Put is synthesized also from agmatine, which is formed from L-arginine by arginine decarboxylase (ADC). Here we demonstrate that the isosteric hydroxylamine analogue of agmatine (AO-Agm) is a new and very potent (IC50 3•10-8 M) inhibitor of E. coli ADC. It was almost two orders of magnitude less potent towards E. coli ODC. AO-Agm decreased polyamine pools and inhibited the growth of DU145 prostate cancer cells only at high concentration (1 mM). Growth inhibitory analysis of the Acremonium chrysogenum demonstrated that the wild type (WT) strain synthesized Put only from L-ornithine, while the cephalosporin C high-yielding strain, in which the polyamine pool is increased, could use both ODC and ADC to produce Put. Thus, AO-Agm is an important addition to the set of existing inhibitors of the enzymes of polyamine biosynthesis, and an important instrument for investigating polyamine biochemistry.

Enzymatic kinetic resolution of desmethylphosphinothricin indicates that phosphinic group is a bioisostere of carboxyl group.

Escherichia coli glutamate decarboxylase (EcGadB), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, is highly specific for L-glutamate and was demonstrated to be effectively immobilised for the production of γ-aminobutyric acid (GABA), its decarboxylation product. Herein we show that EcGadB quantitatively decarboxylates the L-isomer of D,L-2-amino-4-(hydroxyphosphinyl)butyric acid (D,L-Glu-γ-PH), a phosphinic analogue of glutamate containing C-P-H bonds. This yields 3-aminopropylphosphinic acid (GABA-PH), a known GABAB receptor agonist and provides previously unknown D-Glu-γ-PH, allowing us to demonstrate that L-Glu-γ-PH, but not D-Glu-γ-PH, is responsible for D,L-Glu-γ-PH antibacterial activity. Furthermore, using GABase, a preparation of GABA-transaminase and succinic semialdehyde dehydrogenase, we show that GABA-PH is converted to 3-(hydroxyphosphinyl)propionic acid (Succinate-PH). Hence, PLP-dependent and NADP+-dependent enzymes are herein shown to recognise and metabolise phosphinic compounds, leaving unaffected the P-H bond. We therefore suggest that the phosphinic group is a bioisostere of the carboxyl group and the metabolic transformations of phosphinic compounds may offer a ground for prodrug design.

Unforeseen Possibilities To Investigate the Regulation of Polyamine Metabolism Revealed by Novel C-Methylated Spermine Derivatives.

The biogenic polyamines, spermine (Spm) and spermidine, are organic polycations present in millimolar concentrations in all eukaryotic cells participating in the regulation of vital cellular functions including proliferation and differentiation. The design and biochemical evaluation of polyamine analogues are cornerstones of polyamine research. Here we synthesized and studied novel C-methylated Spm analogues: 2,11-dimethylspermine (2,11-Me2Spm), 3,10-dimethylspermine (3,10-Me2Spm), 2-methylspermine, and 2,2-dimethylspermine. The tested analogues overcame growth arrest induced by a 72 h treatment with α-difluoromethylornithine, an ornithine decarboxylase (ODC) inhibitor, and entered into DU145 cells via the polyamine transporter. 3,10-Me2Spm was a poor substrate of spermine oxidase and spermidine/spermine-N1-acetyltransferase (SSAT) when compared with 2,11-Me2Spm, thus resembling 1,12-dimethylspermine, which lacks the substrate properties required for the SSAT reaction. The antizyme (OAZ1)-mediated downregulation of ODC and inhibition of polyamine transport are crucial in the maintenance of polyamine homeostasis. Interestingly, 3,10-Me2Spm was found to be the first Spm analogue that did not induce OAZ1 and, consequently, was a weak downregulator of ODC activity in DU145 cells.

Green and Efficient Esterification Method Using Dried Dowex H+/NaI Approach.

The usefulness of dried Dowex H+ cation-exchange resin with or without sodium iodide (NaI) as a catalyst system for different kinds of esterifications using carboxylic acids and alcohols as starting materials has been systematically investigated. The Dowex H+/NaI approach is very effective, generally high yielding, energy-efficient, and nontoxic, and the Dowex H+ resin is reusable. Since the whole procedure from start to product isolation is also very simple, these features make the method environmentally friendly. The method is regioselective, and its potential for separation of valuable carboxylic acids like resin acids from mixtures containing other kinds of carboxylic acids has been demonstrated. Examples for green and straightforward esterification of highly important natural amino acids are also presented.

Proof of concept for quantitative urine NMR metabolomics pipeline for large-scale epidemiology and genetics.

BACKGROUND: Quantitative molecular data from urine are rare in epidemiology and genetics. NMR spectroscopy could provide these data in high throughput, and it has already been applied in epidemiological settings to analyse urine samples. However, quantitative protocols for large-scale applications are not available. METHODS: We describe in detail how to prepare urine samples and perform NMR experiments to obtain quantitative metabolic information. Semi-automated quantitative line shape fitting analyses were set up for 43 metabolites and applied to data from various analytical test samples and from 1004 individuals from a population-based epidemiological cohort. Novel analyses on how urine metabolites associate with quantitative serum NMR metabolomics data (61 metabolic measures; n = 995) were performed. In addition, confirmatory genome-wide analyses of urine metabolites were conducted (n = 578). The fully automated quantitative regression-based spectral analysis is demonstrated for creatinine and glucose (n = 4548). RESULTS: Intra-assay metabolite variations were mostly <5%, indicating high robustness and accuracy of urine NMR spectroscopy methodology per se. Intra-individual metabolite variations were large, ranging from 6% to 194%. However, population-based inter-individual metabolite variations were even larger (from 14% to 1655%), providing a sound base for epidemiological applications. Metabolic associations between urine and serum were found to be clearly weaker than those within serum and within urine, indicating that urinary metabolomics data provide independent metabolic information. Two previous genome-wide hits for formate and 2-hydroxyisobutyrate were replicated at genome-wide significance. CONCLUSION: Quantitative urine metabolomics data suggest broad novelty for systems epidemiology. A roadmap for an open access methodology is provided.

Effect of salts formed by neutralization for the enzymatic hydrolysis of cellulose and acetone-butanol-ethanol fermentation.

Neutralization is essential to maintain the pH for enzymatic hydrolysis of cellulose followed by fermentation of biofuels. This study investigated the effect of salts formed during the neutralization on the enzymatic hydrolysis of cellulosic materials and acetone-butanol-ethanol (ABE) fermentation. The results showed that the formed Ca-citrate salt considerably decreased the glucose release by 26.9% and 26.1% from Avicel and sulfuric acid-pretreated hybrid Pennisetum, respectively, which was probably due to the unproductive adsorption of cellulases by Ca-citrate solids. On the other hand, the formed soluble Na and Ca salts severely inhibited ABE fermentation, thereby decreasing the ABE concentration from 12.8 g L-1 to 0-10.7 g L-1 in different degrees, but no or slight inhibition was observed when the Ca salts formed as precipitates. In particular, Ca-sulfate did not show apparent inhibition of both hydrolysis and fermentation. Therefore, the selection of suitable pretreatment and neutralizing reagents is an alternative way to avoid process inhibition in biofuel production from lignocellulosic materials.

Controlling the regioselectivity and stereospecificity of FAD-dependent polyamine oxidases with the use of amine-attached guide molecules as conformational modulators.

Enzymes generally display strict stereospecificity and regioselectivity for their substrates. Here by using FAD-dependent human acetylpolyamine oxidase (APAO), human spermine (Spm) oxidase (SMOX) and yeast polyamine oxidase (Fms1), we demonstrate that these fundamental properties of the enzymes may be regulated using simple guide molecules, being either covalently attached to polyamines or used as a supplement to the substrate mixtures. APAO, which naturally metabolizes achiral N1-acetylated polyamines, displays aldehyde-controllable stereospecificity with chiral 1-methylated polyamines, like (R)- and (S)-1-methylspermidine (1,8-diamino-5-azanonane) (1-MeSpd). Among the novel N1-acyl derivatives of MeSpd, isonicotinic acid (P4) or benzoic acid (Bz) with (R)-MeSpd had Km of 3.6 ± 0.6/1.2 ± 0.7 µM and kcat of 5.2 ± 0.6/4.6 ± 0.7 s-1 respectively, while N1 -AcSpd had Km 8.2 ± 0.4 µM and kcat 2.7 ± 0.0 s-1 On the contrary, corresponding (S)-MeSpd amides were practically inactive (kcat < 0.03 s-1) but they retained micromole level Km for APAO. SMOX did not metabolize any of the tested compounds (kcat < 0.05 s-1) that acted as non-competitive inhibitors having Ki ≥ 155 µM for SMOX. In addition, we tested (R,R)-1,12-bis-methylspermine (2,13-diamino-5,10-diazatetradecane) (R,R)-(Me2Spm) and (S,S)-Me2Spm as substrates for Fms1. Fms1 preferred (S,S)- to (R,R)-diastereoisomer, but with notably lower kcat in comparison with spermine. Interestingly, Fms1 was prone to aldehyde supplementation in its regioselectivity, i.e. the cleavage site of spermidine. Thus, aldehyde supplementation to generate aldimines or N-terminal substituents in polyamines, i.e. attachment of guide molecule, generates novel ligands with altered charge distribution changing the binding and catalytic properties with polyamine oxidases. This provides means for exploiting hidden capabilities of polyamine oxidases for controlling their regioselectivity and stereospecificity.

Altered Polyamine Profiles in Colorectal Cancer.

BACKGROUND: The declining mortality rate of patients with colorectal cancer (CRC) can be explained, at least partially, with early diagnosis. Simple diagnostic methods are needed to achieve a maximal patient participation rate in screening. MATERIALS AND METHODS: Liquid chromatography electrospray tandem mass spectrometry (LC-MS/MS) was used to determine urinary polyamine (PA) profiles. In a prospective setting, 116 patients were included in the study: 57 with CRC, 13 with inflammatory bowel disease (IBD), 12 with adenoma, and 34 controls. RESULTS: N1,N12-diacetylspermine (DiAcSPM) level was significantly higher in patients with CRC than controls (sensitivity=78.0%, specificity=70.6%; p=0.00049). The level of diacetylated cadaverine (p=0.0068) was lower and that of diacetylated putrescine (p=0.0078) was higher in patients with CRC than in those with IBD. Cadaverine (p=0.00010) and spermine (p=0.042) levels were lower and that of DiAcSPM (p=0.018) higher in patients with CRC than in those with adenoma. CONCLUSION: The simultaneous determination of urinary PAs by means of LC-MS/MS can be used to discriminate CRC from controls and patients with benign colorectal diseases.

Association between periprosthetic tissue metal content, whole blood and synovial fluid metal ion levels and histopathological findings in patients with failed metal-on-metal hip replacement.

Adverse Reaction to Metal Debris (ARMD) is a major cause of implant failure leading to revision surgery in patients with metal-on-metal (MoM) hip arthroplasties. However, the pathogenesis and its association to implant wear are poorly understood and previous studies have yielded discrepant results. We sought to investigate the associations between histological findings, whole blood and synovial fluid metal ion concentrations and periprosthetic tissue metal concentrations in patients with MoM total hip replacements and hip resurfacings revised for ARMD. 107 hips in total were included in our study. Of these, 87 were total hip replacements and 20 were hip resurfacings, respectively. We found that whole blood, synovial fluid and periprosthetic tissue metal concentrations correlated poorly with histological findings. We suggest that the lack of a clear association between histological findings and wear measures in the present study as well as in previous studies is mostly influenced by variability in patient susceptibility. However, patients presenting with perivascular lymphocytic infiltration had lower chromium concentration in their periprosthetic tissues than patients with no perivascular lymphocytic infiltration. This may reflect the role of metal hypersensitivity in implant failure in these patients. Patients with total hip replacements evinced more necrosis and lymphocytic infiltration in their tissues than patients with hip resurfacings. This suggests that trunnion wear debris is more cytotoxic and/or immunogenic than bearing wear debris leading to higher failure rates seen in patients with total hip replacements.