Absorption and isomerization of caffeoylquinic acids from different foods using ileostomist volunteers.

BACKGROUND: Polyphenols are thought to play important roles in human nutrition and health but these health effects are dependent on their bioavailability. This study is one of a series with the aim of determining possible effects of food matrices on caffeoylquinic acid (CQA) bioavailability using ileostomy volunteers. METHODS: After a CQA-free diet, ileostomists consumed coffee (746 µmol total CQA), and CQAs in excreted ileal fluid were subsequently identified and quantified with HPLC-diode array detection and HPLC-ESI-MS/MS. In our previous studies, other food sources such as cloudy apple juice (CAJ) (358 µmol CQA) and apple smoothie (AS) (335 µmol CQA) were investigated with the same model. RESULTS: Interesterification of CQA from both apple matrices was observed during gastrointestinal passage, whereas CQA consumed in coffee was not influenced by interesterification reactions. In total, 74.3, 22.4, and 23.8 % of the CQA from CAJ, AS, and coffee, respectively, were absorbed or degraded. CONCLUSION: Our results show that variations in food matrices and variations in phenolic composition have a major influence on intestinal bioavailability and interesterification of the investigated subclass of polyphenols, the CQAs.

Review of metastatic spine tumour classification and indications for surgery: the consensus statement of the Global Spine Tumour Study Group.

Choosing the right operation for metastatic spinal tumours is often difficult, and depends on many factors, including life expectancy and the balance of the risk of surgery against the likelihood of improving quality of life. Several prognostic scores have been devised to help the clinician decide the most appropriate course of action, but there still remains controversy over how to choose the best option; more often the decision is influenced by habit, belief and subjective experience. The purpose of this article is to review the present systems available for classifying spinal metastases, how these classifications can be used to help surgical planning, discuss surgical outcomes, and make suggestions for future research. It is important for spinal surgeons to reach a consensus regarding the classification of spinal metastases and surgical strategies. The authors of this article constitute the Global Spine Tumour Study Group: an international group of spinal surgeons who are dedicated to studying the techniques and outcomes of surgery for spinal tumours, to build on the existing evidence base for the surgical treatment of spinal tumours.

Improved metabolic control after 12-week dietary intervention with low glycaemic isomalt in patients with type 2 diabetes mellitus.

The polyol isomalt (Palatinit) is a very low glycaemic sugar replacer. The effect of food supplemented with isomalt instead of higher glycaemic ingredients like sucrose and/or starch hydrolysates on metabolic control in patients with type 2 diabetes was examined in this open study. Thirty-three patients with type 2 diabetes received a diet with foods containing 30 g/d isomalt instead of higher-glycaemic carbohydrates for 12 weeks. Metformin and/or thiazolidindiones were the only concomitant oral antidiabetics allowed during the study. Otherwise, the participants maintained their usual diet during the test phase, but were instructed to refrain from additional sweetened foods. Before start, after 6 weeks and 12 weeks (completion of the study), blood samples were taken and analysed for clinical routine parameters, metabolic, and risk markers. Thirty-one patients completed the study. The test diet was well accepted and tolerated. After 12 weeks, significant reductions were observed for: glycosylated haemoglobin, fructosamine, fasting blood glucose, insulin, proinsulin, C-peptide, insulin resistance (HOMA-IR), and oxidised LDL (an atherosclerosis risk factor). In addition, significant lower nonesterified fatty acid concentrations were found in female participants. Routine blood measurements and blood lipids remained unchanged. The substitution of glycaemic ingredients by isomalt and the consequent on reduction of the glycaemic load within otherwise unchanged diet was accompanied by significant improvement in the metabolic control of diabetes. The present study is in agreement with findings of previous reported studies in human subjects demonstrating beneficial effects of low glycaemic diets on glucose metabolism in patients with diabetes mellitus type 2.

[Oncological surgery of the spine]. / Onkologische Chirurgie der Wirbelsäule.

Spine surgery has been significantly influenced during the past 20 years by improvements in anaesthesia and radiology. This progress has also been promoted by technical developments in spinal instrumentation, mainly the introduction of pedicle screws and anterior support with cages. Both techniques allow correction and stabilisation methods that have had a major effect on tumour surgery. These advancements have allowed less experienced spine surgeons to perform tumour surgery, which may have a negative effect on the outcome. From our point of view, it should be required that tumour surgery be performed only in hospitals managing a certain number of tumours annually. For optimal results, en bloc resection and intralesional marginal resection in particular are highly demanding of the surgeon's technical skills and experience. Second and third operations complicate the intervention unnecessarily. Normally, R0 resection can not be achieved by a second or third revision. For this reason tumour surgery requires a standardised overall concept which must be suited to individual problems. This can be best decided in a tumour board meeting for choosing the options for adjuvant therapy. Only by such a coordinated effort may good mid- and long-term results be achieved.It must be pointed out that en bloc resection is the only surgical therapy that makes a curative approach possible. On the other hand it can also be demonstrated that by making extended, intralesional marginal resections as radical as possible, good mid-term results can be achieved. Here the adjuvant chemo- and radiotherapy play an important role.

[Special gastrointestinal problems of elderly patients]. / Symptomarmer Verlauf--ernste Folgen.

Only a few gastrointestinal diseases develop specifically at advanced ages (e.g. Zenker diverticulum, atrophic gastritis, mesenterial ischaemia). However, the frequency of certain diseases increases and various illnesses are found to take other, mostly silent, courses in elderly people. As a rule, more complications in gastrointestinal diseases are to be expected and the presence of comorbidities can make diagnosis and therapy more difficult. The possibility of tumours should always be considered in the differential diagnosis of elderly patients. The diagnosis and treatment of elderly patients for gastrointestinal diseases are no different from that of other age groups.

SNP-Array genotyping and spectral karyotyping reveal uniparental disomy as early mutational event in MSS- and MSI-colorectal cancer cell lines.

In this study nine colorectal cancer cell lines were analysed by 10K SNP-arrays and spectral karyotyping (SKY). Complex chromosomal alterations and breakpoints of deleted or translocated fragments found by SKY could further be characterized by SNP-array analysis. Interestingly many monoallelic regions identified by SNP-array analysis display no copy number alterations, representing uniparental disomy (UPD). It was demonstrated that UPD seems to be involved in activation of early-acting tumor suppressor genes in MSS- (APC, CDKN2A) and MSI- (MLH1, MSH2, APC, CDKN2A) colorectal cancer cell lines. Genes involved later on in the adenoma-carcinoma sequence (i.e. TP53/SMAD4) were not found to be inactivated by UPD. Furthermore, identified amplified monoallelic regions may include oncogenes activated by allele-specific-amplification (i.e. Cyclin D1). However, at present, the majority of the monoallelic regions located in the present study have not yet been associated with known tumor suppressor genes and oncogenes. Further studies are warranted to identify relevant genes in the respective regions and to further verify the results presented here.

[The role of the diet in the prevention of gastrointestinal tumors]. / Ernährungstipps zur Prävention gastrointestinaler Tumoren. Obst und Gemüse sind die Favoriten.

Second only to cardiovascular diseases, malignant tumors are the most common fatal disease, with malignant neoplasms in the gastrointestinal tract playing an important role. Underlying the most numerous of these malignancies is a complex interaction between genetic and environmental factors. The data relating to the role of environmental factors (for the most part dietary factors) in the development of gastrointestinal tumors derive mainly from, epidemiological research. The current evidence is "convincin" with regard to complex lifestyle patterns, but at most "plausible" when the chemically defined individual substances are considered. Summarizing the potential protective value of dietary factors reveals that the risk of contracting the majority of the gastrointestinal tumors can be reduced by increasing the intake of fruit and vegetables. An additional protective effect is associated with a balanced diet, physical activity, preservation of normal weight, avoidance of smoking, and moderation in the amount of alcohol consumed.

Evaluation of the reject waters from co-digestion of solid wastes from agro-industries in a municipal WWTP.

Overcapacities of anaerobic digesters at municipal WWTPs are frequently used for the treatment of organic wastes in order to increase the biogas production. However, "co-digestion" of organic wastes leads to additional nitrogen loading and to additional loads of non-biodegradable COD. The effects of (co-) digestion of organic wastes from agro-industries (slaughterhouses, dairies and leather industry) on the wastewater cycle have been evaluated in full-scale investigations at Leoben WWTP with a capacity of 90,000 pe where the methane production was increased from 700 to more than 1700 Nm3 CH4 per day. For this evaluation, mass balances for COD and nitrogen have been applied to estimate the fluxes of these substances. Application of this method is described in detail. As the additional loadings, it was found that related to methane production less nitrogen is released from the organic wastes than from the waste sludge. While the ammonia nitrogen load in the effluent from sludge digestion was about 100 g NH4-N per Nm3 of CH4 produced, in the effluent from the digestion of organic wastes only 70 g NH4-N/Nm3 CH4 were found. The decrease in the COD removal efficiency after digestion of the organic wastes started was not regarded as significant enough to be seen as a consequence of the treatment of external substrate.

[Anatomic reduction and monosegmental fusion for high-grade developmental spondylolisthesis L5/S1]. / Anatomische Reposition und monosegmentale Fusion bei hochgradiger dysplastischer Spondylolisthese L5/S1.

INTRODUCTION: Developmental spondylolisthesis leads to lumbosacral kyphosis with retroversion of the sacrum and lumbar hyperlordosis. The overall sagittal profile of the spine is affected. The deformity is progressive during growth. This retrospective study describes a technique for complete reduction with clinical and radiological evaluation. PATIENTS: Thirty-four patients (mean age 16 years 3 months, 10 males, 24 females) with severe developmental spondylolisthesis L5/S1 (Meyerding grades 3 to 5) were operated on between February 1997 and July 2002. METHOD: Reduction was achieved by temporary transpedicular instrumentation of L4. These screws were removed at the end of the operation or 12 weeks later. RESULTS: Mean slippage was corrected from 76 % preoperatively to 10 % postoperatively. Segmental kyphosis L5/S1 improved from + 21 degrees preoperatively to - 7 degrees postoperatively. Sacral inclination was 34 degrees preoperatively, 43 degrees postoperatively, and 47 degrees at latest follow-up. 76 % of the patients were pain free at the latest follow-up. In 4 patients a fusion at L4/5 was performed due to subsequent decompensation. CONCLUSION: The technique described allows for a nearly anatomic reduction with correction of slippage as well as segmental kyphosis. Correction of the local deformity with monosegmental fusion L5/S1 improves dramatically the overall sagittal profile of the spine. Fusion of the primarily healthy segment L4/5 can be avoided.

Effects of isomalt consumption on gastrointestinal and metabolic parameters in healthy volunteers.

The polyol isomalt (Palatinit) is a well established sugar replacer. The impact of regular isomalt consumption on metabolism and parameters of gut function in nineteen healthy volunteers was examined in a randomised, double-blind, cross-over trial with two 4-week test periods. Volunteers received 30 g isomalt or 30 g sucrose daily as part of a controlled diet. In addition to clinical standard diagnostics, biomarkers and parameters currently discussed as risk factors for CHD, diabetes or obesity were analysed. Urine and stool Ca and phosphate excretions were measured. In addition, mean transit time, defecation frequency, stool consistency and weight were determined. Consumption of test products was affirmed by the urinary excretion of mannitol. Blood lipids were comparable in both phases, especially in volunteers with hyperlipidaemia, apart from lower apo A-1 (P=0.03) for all subjects. Remnant-like particles, oxidised LDL, NEFA, fructosamine and leptin were comparable and not influenced by isomalt. Ca and phosphate homeostasis was not affected. Stool frequency was moderately increased in the isomalt phase (P=0.006) without changes in stool consistency and stool water. This suggests that isomalt is well tolerated and that consumption of isomalt does not impair metabolic function or induce hypercalciuria. In addition, the study data indicate that isomalt could be useful in improving bowel function.

Expression of the cathelicidin LL-37 is modulated by short chain fatty acids in colonocytes: relevance of signalling pathways.

BACKGROUND AND AIMS: Short chain fatty acids (SCFA) exert profound effects on the colonic mucosa. In particular, SCFA modulate mucosal immune functions. The antimicrobial cathelicidin LL-37 is expressed by colon epithelial cells. In the present study the effect of SCFA on LL-37 expression was investigated. METHODS: LL-37 expression in vivo was assessed by immunohistochemistry. Real time quantitative reverse transcription-polymerase chain reaction was employed to determine LL-37 expression in colonocytes in vitro after treatment with various cytokines, SCFA, or flavone. LL-37 levels were correlated to cell differentiation which was determined by alkaline phosphatase (AP) activity. In addition, intracellular signalling pathways such as MEK-ERK (mitogen/extracellular signal protein kinase (MEK)/extracellular signal regulated protein kinase (ERK)) and p38/mitogen activated protein (MAP) kinase were explored. RESULTS: In vivo, LL-37 expression in healthy mucosa was restricted to differentiated epithelial cells in human colon and ileum. In colonocytes, increased LL-37 expression associated with cell differentiation was detected in vitro following treatment with butyrate, isobutyrate, propionate, and trichostatin A. Flavone induced LL-37 transcription but did not affect AP activity while cytokines had no effect. To dissect pathways mediating differentiation and LL-37 expression, specific inhibitors were applied. Inhibition of the protein kinase MEK enhanced butyrate induced AP activity while LL-37 expression in colon epithelial cells was blocked. In contrast, inhibition of p38/MAP kinase blocked cell differentiation without inhibiting LL-37 expression. CONCLUSIONS: Expression of the cathelicidin LL-37 in colonocytes and cellular differentiation are separately modulated by SCFA via distinct signalling pathways. These data may provide a rationale for dietary modulation of mucosal defence mechanisms.

Butyrate and aspirin in combination have an enhanced effect on apoptosis in human colorectal cancer cells.

Laboratory and epidemiological studies suggest that butyrate, a metabolic product of microbial fermentation of dietary fibre, and aspirin, a non-steroidal antiphlogistic drug, both reduce the risk of developing colon cancer. Notably, few data exist on potential interactions of these two substances. In this study, the effects of a butyrate-aspirin combination on human colon cancer cells were compared with treatment with aspirin or butyrate alone. Both substances decreased proliferation and induced differentiation and apoptosis. Butyrate reduced mutant p53 expression, whereas aspirin did not affect p53 expression. Butyrate-induced apoptosis correlated with an increase in Bak expression and a decrease in the expression of Bcl-XL. Aspirin had no effect on the investigated apoptosis-controlling factors. The antiproliferative and pro-apoptotic effects of the butyrate-aspirin combination were markedly enhanced. The combination resulted in a stronger decrease in the expression of PCNA and cdk2. Our data suggest that the anticarcinogenic effect of aspirin might effectively be augmented by combination with the short-chain fatty acid butyrate.

Butyrate inhibits NF-kappaB activation in lamina propria macrophages of patients with ulcerative colitis.

BACKGROUND: In ulcerative colitis (UC) the activation (i.e. nuclear translocation) of nuclear factor kappa B (NF-kappaB) is an important step in the regulation of cytokines secreted by lamina propria macrophages. Clinical trials suggest anti-inflammatory effects of locally administered butyrate in UC. The potential effects of butyrate on NF-kappaB activation in lamina propria macrophages of UC patients were investigated. METHODS: Eleven patients with distal UC were treated for up to 8 weeks with butyrate at 100 mM (n = 6) or placebo (n = 5) enemas. At entry and after 4 and 8 weeks, clinical status was noted and intestinal inflammation was graded endoscopically and histologically. Double-staining with antibodies against NF-kappaB (p65) and CD68 was employed to detect NF-kappaB and macrophages, respectively. RESULTS: In untreated patients, nuclear translocation of NF-kappaB was detectable in virtually all macrophages. Butyrate treatment for 4 and 8 weeks resulted in a significant reduction in the number of macrophages being positive for nuclear translocated NF-kappaB. In addition, butyrate significantly reduced both the number of neutrophils in crypt and surface epithelia and of the lamina propria lymphocytes/plasma cells. These findings correlated with a significant decrease in the Disease Activity Index (DAI). CONCLUSIONS: The decrease in DAI and mucosal inflammation in butyrate-treated patients is associated with a reduction of NF-kappaB translocation in lamina propria macrophages. Since the inflammatory process in UC is mainly sustained by macrophage-derived cytokines, the known anti-inflammatory effects of butyrate may in part be mediated by an inhibition of NF-kappaB activation in these macrophages.

Spectral karyotype analysis of colon cancer cell lines of the tumor suppressor and mutator pathway.

BACKGROUND AND AIMS: Microsatellite instability (MSI) is characterized by the size variation of microsatellites in tumor DNA as compared to matching normal DNA due to defects in the mismatch repair system. To examine the chromosomal differences in microsatellite-stable (MSS) and -unstable (MSI) tumors in detail, we analyzed MSS (Caco-2, Colo-205, SW948) and MSI (HCT-15, HCT-116, LoVo) cell lines by spectral karyotyping (SKY). METHODS: SKY is a sensitive method to detect chromosome aberrations by visualizing each chromosome in a different color. Metaphases were hybridized with a SKY probe mixture. Images were visualized with the SpectraCube system and analyzed with the SKYview imaging software. RESULTS: The average number of chromosomes was 49 in LoVo, 45 in HCT-116, 46 in HCT-15, 71 in Colo-205, 89 in Caco-2 and 66 in SW-948. Three aberrant chromosomes were detected in LoVo, three in HCT-116, two in HCT-15, seventeen in Colo-205, fourteen in Caco-2 and nine in SW948. CONCLUSION: The karyotypes of MSS colon cancer cells displayed complex numerical and structural aberrations. In contrast the chromosomes of MSI colon cancer cells were mostly unaltered but displayed a few isolated numerical and structural aberrations. We speculate that these isolated aberrations may be specifically involved in the pathogenesis of MSI tumors.

Posterior C1-C2 fusion with polyaxial screw and rod fixation.

STUDY DESIGN: A novel technique of atlantoaxial stabilization using individual fixation of the C1 lateral mass and the C2 pedicle with minipolyaxial screws and rods is described. In addition, the initial results of this technique on 37 patients are described. OBJECTIVES: To describe the technique and the initial clinical and radiographic results for posterior C1-C2 fixation with a new implant system. SUMMARY OF BACKGROUND DATA: Stabilization of the atlantoaxial complex is a challenging procedure because of the unique anatomy of this region. Fixation by transarticular screws combined with posterior wiring and structural bone grafting leads to excellent fusion rates. The technique is technically demanding and has a potential risk of injury to the vertebral artery. In addition, this procedure cannot be used in the presence of fixed subluxation of C1 on C2 and in the case of an aberrant path of the vertebral artery. To address these limitations, a new technique of C1-C2 fixation has been developed: bilateral insertion of polyaxial-head screws in the lateral mass of C1 and through the pars interarticularis into the pedicle of C2, followed by a fluoroscopically controlled reduction maneuver and rod fixation. METHODS: After posterior exposure of the C1-C2 complex, the 3.5-mm polyaxial screws are inserted in the lateral masses of C1. Two polyaxial screws are then inserted into the pars interarticularis of C2. Drilling is guided by anatomic landmarks and fluoroscopy. If necessary, reduction of C1 onto C2 can be accomplished by manipulation of the implants, followed by fixation to the 3-mm rod. For definitive fusion, cancellous bone can be added. No structural bone graft or wiring is required. In selected cases, e.g., C1-C2 subluxation or fractures in young patients in whom only temporary fixation is necessary, the instrumentation can be removed after an appropriate time. Because the joint surfaces stay intact, the patient can regain motion in the C1-C2 joints. RESULTS: Thirty-seven patients underwent this procedure. No neural or vascular damage related to this technique has been observed. The early clinical and radiologic follow-up data indicate solid fusion in all patients. CONCLUSION: Fixation of the atlantoaxial complex using polyaxial-head screws and rods seems to be a reliable technique and should be considered an efficient alternative to the previously reported techniques.

Butyrate inhibits interleukin-1-mediated nuclear factor-kappa B activation in human epithelial cells.

Nuclear factor-kappa B (NF-kappaB) is a critical transcription factor for the inducible expression of multiple genes involved in inflammation. NF-kappaB is sequestered in the cytoplasm by inhibitory IkappaB proteins. Extracellular stimuli, notably interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) activate NF-kappaB nuclear translocation via IkappaB phosphorylation and degradation. Since previous reports suggest that the short chain fatty acid butyrate has antiinflammatory properties, the effects of butyrate on NF-kappaB nuclear translocation in human epithelial cells (HeLa229) were tested. In cells pretreated with butyrate, a time- and dose-dependent inhibition of IL-1beta-mediated NF-kappaB nuclear translocation was observed. However, IkappaB alpha phosphorylation and degradation occurred rapidly in both butyrate pretreated and nonpretreated cells, respectively. These data indicate that inhibition of IL-1beta-induced NF-kappaB activation by butyrate does not require an intact IkappaB alpha protein.

Stability of ketone bodies in serum in dependence on storage time and storage temperature.

The serum concentrations of beta-hydroxybutyrate and acetoacetate as well as the beta-hydroxybutyrate/acetoacetate ratio are important parameters for the differential diagnosis of certain inborn errors of metabolism. Acetoacetate, however, is an unstable compound which becomes rapidly decarboxylated. At a storage temperature of -20 degrees C about 40% of the acetoacetate is lost within 7 days and after 40 days storage at this temperature virtually all of the acetoacetate has become degraded. At -80 degrees C the decomposition of acetoacetate occurs with a much slower rate and only 15% of the initial acetoacetate is lost after 40 days storage. The rate constants for the decarboxylation reaction were found to be (6.4 +/- 2.9) * 10(-5) [min(-1)] at -20 degrees C and (0.4 +/- 0.3) * 10(-5) [min(-1)] at -80 degrees C. In contrast, beta-hydroxybutyrate is very stable during storage and hence should be used as main parameter for the evaluation of ketonemia. If determination of acetoacetate and/or of the beta-hydroxybutyrate/acetoacetate ratio is necessary, an assay immediately after collecting the serum samples is recommended. Otherwise, the serum samples should be frozen as soon as possible and stored at -80 degrees C during transport and storage.

Cytokine-activated degradation of inhibitory kappaB protein alpha is inhibited by the short-chain fatty acid butyrate.

Butyrate, a short-chain fatty acid, is generated by anaerobic fermentation within the colon. Clinical trials suggest that short-chain fatty acids ameliorate inflammation in ulcerative colitis. Nuclear factor (NF) kappaB, an inducible transcription factor that is activated in inflamed colonic tissue, is sequestered to the cytoplasm by its inhibitory IkappaB proteins. The anti-inflammatory effects of butyrate are associated with an inhibition of NF-kappaB nuclear translocation. To investigate the mechanism of NF-kappaB inhibition we examined the effects of butyrate on IkappaBalpha. Human adenocarcinoma cells (SW480, SW620, and HeLa229) were treated with butyrate for up to 48 h followed by tumor necrosis factor (TNF) alpha stimulation. NF-kappaB was detected by immunofluorescence staining with an antibody against its p65 subunit. Levels of IkappBalpha and phosphorylated IkappaBalpha were determined by western blot. Stimulation with TNFalpha resulted in rapid phosphorylation and degradation of IkappaBalpha followed by NF-kappaB nuclear translocation. Butyrate pretreatment successfully inhibited NF-kappaB activation. Pretreatment of adenocarcinoma cells with butyrate is associated with inhibition of TNFalpha-mediated phosphorylation and degradation of IkappaBalpha and effective blocking of NF-kappaB nuclear translocation. The anti-inflammatory effects of butyrate may at least in part be mediated by an inhibition of IkappaBalpha mediated activation of NF-kappaB.