Comparing wire-mesh sensor with neutron radiography for measurement of liquid fraction in foam.

The liquid fraction of foam is an important quantity in engineering process control and essential to interpret foam rheology. Established measurement tools for the liquid fraction of foam, such as optical measurement or radiography techniques as well as weighing the foam, are mostly laboratory-based, whereas conductivity-based measurements are limited to the global measurement without detailed spatial information of liquid fraction. In this work, which combines both types of measurement techniques, the conductivity-based wire-mesh sensor is compared with neutron radiography. We found a linear dependency between the liquid fraction of the foam and the wire-mesh readings with a statistical deviation less than 15%. However, the wire-mesh sensor systematically overestimates the liquid fraction, which we attribute to liquid bridge formation between the wires.

Fatty acid composition of adipose tissue at term indicates deficiency of arachidonic and docosahexaenoic acid and excessive linoleic acid supply in preterm infants.

BACKGROUND: Arachidonic (ARA) and docosahexaenoic acid (DHA) are constitutive to membrane phospholipids, and essential for brain and overall development. ARA/DHA pools in term infants (TI) are built during the third trimester, stored as adipose tissue triglycerides and predominantly distributed via plasma phosphatidylcholine (PC). In preterm infants (PTI), placental ARA/DHA supply is replaced by linoleic-acid (LA)-enriched nutrition. This study aimed to investigate the impact of PTI nutrition, compared to placental supply, on fatty acid composition in adipose tissue and blood. METHODS: Prospective observational study (4/2017-3/2019) in 12 PTI and 3 PTI with enterostomy (PTI/E) (gestational age (GA) < 32 weeks) with surgical intervention at term (± 6 weeks) and 14 TI (GA ≥ 34 weeks, surgical intervention < 2 weeks postnatally). PTI/E were analyzed descriptively only. PC and triglyceride fatty acids were analyzed with tandem mass spectrometry and gas chromatography, respectively. Results were compared between TI and PTI with Wilcoxon Test and shown as median [25th percentile-75th percentile] mol%. RESULTS: PTI had less ARA in adipose tissue TG (0.77[0.67-0.87]% vs. 1.04[0.95-1.14]%, p = 0.0003) and plasma PC (20.7[18.7-22.8]% vs. 28.3[22.7-33.5]%, p = 0.011) than TI. PTI also had less DHA in adipose tissue TG (0.6[0.4-0.8]% vs. 1.1[0.8-1.4]%, p = 0.006) and plasma PC (6.4[5.6-7.1]% vs. 8.4[7.8-13.1]%, p = 0.002). LA was increased in PTI's adipose tissue TG (10.0[8.8-12.3]% vs. 3.0[2.5-3.6]%, p < 0.0001) and plasma PC (48.4[44.6-49.6]% vs. 30.6[24.9-35.6]%, p = 0.0002). Similar differences were observed in erythrocyte PC. CONCLUSION: In PTI, LA is increased and ARA/DHA decreased in adipose tissue, plasma and erythrocyte lipids as proxies for other tissues, likely caused by PTI nutrition. This may contribute to impaired PTI development.

Epigenetic activation of O-linked ß-N-acetylglucosamine transferase overrides the differentiation blockage in acute leukemia.

BACKGROUND: Overriding the differentiation blockage in acute myeloid leukemia (AML) is the most successful mode-of-action in leukemia therapy - now curing the vast majority of patients with acute promyelocytic leukemia (APL) using all-trans retinoic acid (ATRA)-based regimens. Similar approaches in other leukemia subtypes, such as IDH1/2-mutated AML, are under active investigation. We herein present successful release of the differentiation blockage upon treatment with the natural (-)-Δ9-Tetrahydrocannabinol isomer dronabinol in vitro and in vivo. METHODS: Cellular maturation and differentiation were followed in two patients employing whole genome methylation profiling, proteome analyses, NGS deep sequencing and multispectral imaging flow cytometry. For functional studies lentiviral OGT knock-down in vitro and ex vivo cell models were created to evaluate proliferative, apoptotic and differentiating effects of OGT in acute leukemia. FINDINGS: In here, we provide molecular evidence that dronbinol is capable to override the differentiation blockage of acute leukemia blasts at the state of the leukemia-initiating clone. We further identify the O-linked ß-N-acetyl glucosamine (O-GlcNAc) transferase (OGT) to be crucial in this process. OGT is a master regulator enzyme adding O-GlcNAc to serine or threonine residues in a multitude of target proteins. Aberrant O-GlcNAc modification is implicated in pathologies of metabolic, neurodegenerative and autoimme diseases as well as cancers. We provide evidence that dronabinol induces transcription of OGT via epigenetic hypomethylation of the transcription start site (TSS). A lentiviral OGT-knock out approach proves the central role of OGT exerting antileukemic efficacy via a dual-mechanism of action: High concentrations of dronabinol result in induction of apoptosis, whereas lower concentrations drive cellular maturation. Most intriguingly, overriding of the differentiation blockage of acute leukemia blasts is validated in vivo following two patients treated with dronabinol. INTERPRETATION: In conclusion, we provide evidence for overcoming the differentiation blockage in acute leukemia in subentities beyond promyelocytic and IDH1/2-mutated leukemia and thereby identify O-GlcNAcylation as a novel (drugable) field for future leukemia research. FUNDING: Unrestricted grant support by the IZKF Program of the Medical Faculty Tübingen (MMS) and Brigitte Schlieben-Lange Program as well as the Margarete von Wrangell Program of the Ministry of Science, Research and the Arts, Baden-Württemberg, Germany (KKS) and Athene Program of the excellence initiative University of Tübingen (KKS).

The protective effect of human renal sinus fat on glomerular cells is reversed by the hepatokine fetuin-A.

Renal sinus fat (RSF) is a perivascular fat compartment located around renal arteries. In this in vitro and in vivo study we hypothesized that the hepatokine fetuin-A may impair renal function in non alcoholic fatty liver disease (NAFLD) by altering inflammatory signalling in RSF. To study effects of the crosstalk between fetuin-A, RSF and kidney, human renal sinus fat cells (RSFC) were isolated and cocultured with human endothelial cells (EC) or podocytes (PO). RSFC caused downregulation of proinflammatory and upregulation of regenerative factors in cocultured EC and PO, indicating a protective influence of RFSC. However, fetuin-A inverted these benign effects of RSFC from an anti- to a proinflammatory status. RSF was quantified by magnetic resonance imaging and liver fat content by 1H-MR spectroscopy in 449 individuals at risk for type 2 diabetes. Impaired renal function was determined via urinary albumin/creatinine-ratio (uACR). RSF did not correlate with uACR in subjects without NAFLD (n = 212, p = 0.94), but correlated positively in subjects with NAFLD (n = 105, p = 0.0005). Estimated glomerular filtration rate (eGRF) was inversely correlated with RSF, suggesting lower eGFR for subjects with higher RSF (r = 0.24, p < 0.0001). In conclusion, our data suggest that in the presence of NAFLD elevated fetuin-A levels may impair renal function by RSF-induced proinflammatory signalling in glomerular cells.

Medium-chain fatty acids modulate myocardial function via a cardiac odorant receptor.

Several studies have demonstrated the expression of odorant receptors (OR) in various human tissues and their involvement in different physiological and pathophysiological processes. However, the functional role of ORs in the human heart is still unclear. Here, we firstly report the functional characterization of an OR in the human heart. Initial next-generation sequencing analysis revealed the OR expression pattern in the adult and fetal human heart and identified the fatty acid-sensing OR51E1 as the most highly expressed OR in both cardiac development stages. An extensive characterization of the OR51E1 ligand profile by luciferase reporter gene activation assay identified 2-ethylhexanoic acid as a receptor antagonist and various structurally related fatty acids as novel OR51E1 ligands, some of which were detected at receptor-activating concentrations in plasma and epicardial adipose tissue. Functional investigation of the endogenous receptor was carried out by Ca2+ imaging of human stem cell-derived cardiomyocytes. Application of OR51E1 ligands induced negative chronotropic effects that depended on activation of the OR. OR51E1 activation also provoked a negative inotropic action in cardiac trabeculae and slice preparations of human explanted ventricles. These findings indicate that OR51E1 may play a role as metabolic regulator of cardiac function.

A microwave resonator integrated on a polymer microfluidic chip.

We describe a novel stacked split-ring type microwave (MW) resonator that is integrated into a 10mm by 10mm sized microfluidic chip. A straightforward and scalable batch fabrication process renders the chip suitable for single-use applications. The resonator volume can be conveniently loaded with liquid sample via microfluidic channels patterned into the mid layer of the chip. The proposed MW resonator offers an alternative solution for compact in-field measurements, such as low-field magnetic resonance (MR) experiments requiring convenient sample exchange. A microstrip line was used to inductively couple MWs into the resonator. We characterised the proposed resonator topology by electromagnetic (EM) field simulations, a field perturbation method, as well as by return loss measurements. Electron paramagnetic resonance (EPR) spectra at X-band frequencies were recorded, revealing an electron-spin sensitivity of 3.7·10(11)spins·Hz(-1/2)G(-1) for a single EPR transition. Preliminary time-resolved EPR experiments on light-induced triplet states in pentacene were performed to estimate the MW conversion efficiency of the resonator.

Effect of metformin on methylglyoxal metabolism in patients with type 2 diabetes.

The effect of metformin on methylglyoxal (MG) metabolism was studied in a prospective non-randomized 24 weeks trial in patients with type 2 diabetes.Metformin treatment, in addition to life style intervention, significantly reduced morning glucose and HbA1c whilst body weight and BMI were only marginally reduced during the 24 week trial. Treatment significantly reduced both plasma MG and carboxymethyl-lysine (CML), a marker of oxidative stress. The reduction in MG was paralleled by a significant increase in the activity of Glyoxalase 1 (Glo1), the major route of MG detoxification, in peripheral blood mononuclear cells and red blood cells. Multivariate analysis showed that the changes in MG were dependent upon the metformin treatment.This study supports previous findings that metformin can reduce plasma MG in type 2 diabetic patients. However, given the observed increase in Glo1 activity, this reduction is due not only to the scavenging properties of metformin, but the restoration of Glo1 activity.

Exercise-induced albuminuria is associated with perivascular renal sinus fat in individuals at increased risk of type 2 diabetes.

AIMS/HYPOTHESIS: Microalbuminuria represents an established surrogate marker of early diabetic nephropathy and glomerular microangiopathy. Increasing evidence is emerging of a role of perivascular adipose tissue (PVAT) as an important link between obesity, insulin resistance and both macro- and microangiopathy. It is not known whether perivascular renal sinus fat (RSF) has an impact on microalbuminuria in the prediabetic stage. We investigated whether RSF quantified by MRI is associated with microalbuminuria before or after exercise. METHODS: Non-diabetic individuals at increased risk of type 2 diabetes were recruited into the Tübingen Lifestyle Intervention Program (TULIP); 146 participants took part in the analysis. RSF was measured in axial MRI sections at the level of the renal artery. Urine was collected before and after exercise stress testing. RESULTS: Participants (age 47 ± 12 years; mean ± SD) reached a mean exercise load of 176 ± 49 W, with a mean arterial peak pressure (MAPP) of 112 ± 14 mmHg. After adjusting for sex, age, visceral adipose tissue (VAT) and MAPP during exercise, RSF was significantly associated with postexercise albumin/creatinine ratio (ACR; p = 0.006). No association between RSF and baseline BP could be observed after adjusting for confounders (p = 0.26), and there was no association between RSF and baseline ACR either (p = 0.2). CONCLUSIONS: RSF is associated with exercise-induced albuminuria independently of sex, age, VAT and MAPP in a non-diabetic cohort at diabetic risk. We conclude that PVAT in the renal sinus may play a role in the pathogenesis of microalbuminuria.

High cerebral insulin sensitivity is associated with loss of body fat during lifestyle intervention.

AIMS/HYPOTHESIS: Loss of weight and body fat are major targets in lifestyle interventions to prevent diabetes. In the brain, insulin modulates eating behaviour and weight control, resulting in a negative energy balance. This study aimed to test whether cerebral insulin sensitivity facilitates reduction of body weight and body fat by lifestyle intervention in humans. METHODS: The study was performed as an additional arm of the TUebingen Lifestyle Intervention Program (TULIP). In 28 non-diabetic individuals (14 female/14 male; mean ± SE age 42 ± 2 years; mean ± SE BMI 29.9 ± 0.8 kg/m²), we measured cerebrocortical insulin sensitivity by using magnetoencephalography before lifestyle intervention. Total and visceral fat were measured by using MRI at baseline and after 9 months and 2 years of lifestyle intervention. RESULTS: Insulin-stimulated cerebrocortical theta activity at baseline correlated with a reduction in total adipose tissue (r = -0.59, p = 0.014) and visceral adipose tissue (r = -0.76, p = 0.001) after 9 months of lifestyle intervention, accompanied by a statistical trend for reduction in body weight change (r = -0.37, p = 0.069). Similar results were obtained after 2 years. CONCLUSIONS/INTERPRETATION: Our results suggest that high insulin sensitivity of the human brain facilitates loss of body weight and body fat during lifestyle intervention.

Association of changes in body mass index during earlier adulthood and later adulthood with circulating obesity biomarker concentrations in middle-aged men and women.

AIMS/HYPOTHESIS: The objective of our study was to investigate whether changes in BMI during earlier adulthood are more strongly associated with levels of circulating obesity biomarkers in middle age than are BMI changes during later adulthood. METHODS: The study included 1,612 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. The associations of BMI changes based on recalled BMI for the age ranges 25-40 years (earlier adulthood) and 40-55 years (later adulthood) with later biomarker levels were compared using a linear model, adjusted for BMI at age 25 years and conventional risk factors. RESULTS: BMI changes during both time periods as well as BMI at age 25 years were significantly associated with circulating levels of adiponectin, γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), high-sensitivity C-reactive protein (hs-CRP) and HDL-cholesterol (HDL-C) in both sexes, and of HbA(1c) in women. However, BMI gain for the age range 25-40 years was significantly more strongly associated with unfavourable levels of adiponectin, hs-CRP, HDL-C and HbA(1c) in men and women, and of GGT and ALT in men (p difference <0.05) than BMI gain for the age range 40-55 years. The percentage change in biomarker levels per unit gain in BMI for the age range 25-40 years ranged from 0.81% (HbA(1c)) to 9.80% (hs-CRP) in men, and from 0.75% (HbA(1c)) to 14.7% (hs-CRP) in women, whereas for the age range 40-55 years, values ranged from -0.15% to 4.82% in men and from 0.25% to 7.06% in women. CONCLUSIONS/INTERPRETATION: The results support the hypothesis that an increase in BMI in earlier adulthood is more strongly associated with unfavourable circulating levels of obesity biomarkers later in life than is an increase in BMI in later adulthood.

Diagnostic value of hemoglobin A1c for type 2 diabetes mellitus in a population at risk.

OBJECTIVE: Because the American Diabetes Association has recently included HbA1c as the primary diagnostic test for the detection of diabetes mellitus (HbA1c ≥6.5%) we investigated its use as screening parameter for diabetes in a cohort at increased risk for the disease. RESEARCH DESIGN AND METHODS: During the last 10 years 2 036 Caucasians at risk to develop type 2 diabetes but not having this diagnosis yet, consecutively underwent a 75 g oral glucose tolerance test (OGTT). HbA1c was determined with the HPLC method (Tosoh A1c 2.2), external and internal quality controls were well within the allowed ranges. RESULTS: The oral glucose tolerance test classified 1 523 individuals as normal glucose tolerant (NGT), 387 as impaired glucose tolerant (IGT) or having impaired fasting glycemia (IFG) and 126 as diabetic. The 6.5% cut-off value of HbA1c classified 47% of the diabetic individuals correctly. Of the remaining 53% diabetic individuals (HbA1c <6.5%) 35% had increased fasting glucose levels, while 65% were only diagnosed by their increased 2 h glucose values. CONCLUSION: A cut-off value of 6.5% HbA1c classifies diabetic subjects with a specificity of 98.7%. However, the sensitivity of 46.8% is low, indicating that more than half of diabetic subjects are missed when using this test. The present data shows that the use of HbA1c as a the primary diagnostic test will reduce diabetes prevalence. Furthermore, it suggests, that HbA1c and OGTT measurements cannot simply be exchanged, but most probably detect and define different categories of diabetes, i. e., categories with different risk of cardiovascular disease.

IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise.

AIMS/HYPOTHESIS: Fasting and exercise are strong physiological stimuli for hepatic glucose production. IL-6 has been implicated in the regulation of gluconeogenic genes, but the results are contradictory and the relevance of IL-6 for fasting- and exercise-induced hepatic glucose production is not clear. METHODS: Investigations were performed in rat hepatoma cells, and on C57Bl6 and Il6(-/-) mice under the following conditions: IL-6 stimulation/injection, non-exhaustive exercise (60 min run on a treadmill) and fasting for 16 h. Metabolite analysis, quantitative real-time PCR and immunoblotting were performed. RESULTS: IL-6 stimulation of rat hepatoma cells led to higher glucose production. Injection of IL-6 in mice slightly increased hepatic Pepck (also known as Pck1) expression. Fasting of Il6(-/-) mice for 16 h did not alter glucose production compared with wild-type mice, since plasma glucose concentrations were similar and upregulation of phosphoenolpyruvate carboxykinase (PEPCK) and Pgc-1alpha (also known as Ppargc1a) expression was comparable. In the non-fasting state, Il6(-/-) mice showed a mild metabolic alteration including higher plasma glucose and insulin levels, lower NEFA concentrations and slightly increased hepatic PEPCK content. Moderately intense exercise resulted in elevated IL-6 plasma levels in wild-type mice. Despite that, plasma glucose, insulin, NEFA levels and hepatic glycogen content were not different in Il6(-/-) mice immediately after running, while expression of hepatic G6pc, Pgc-1alpha, Irs2 and Igfbp1 mRNA was similarly increased. CONCLUSIONS/INTERPRETATION: These data suggest that in mice IL-6 is not essential for physiologically increased glucose production during fasting or non-exhaustive exercise.

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise.

AIMS/HYPOTHESIS: We aimed to identify, in the liver of mice, signal transduction pathways that show a pronounced regulation by acute exercise. We also aimed to elucidate the role of metabolic stress in this response. METHODS: C57Bl6 mice performed a 60 min run on a treadmill under non-exhaustive conditions. Hepatic RNA and protein lysates were prepared immediately after running and used for whole-genome-expression analysis, quantitative real-time PCR and immunoblotting. A subset of mice recovered for 3 h after the treadmill run. A further group of mice performed the treadmill run after having received a vitamin C- and vitamin E-enriched diet over 4 weeks. RESULTS: The highest number of genes differentially regulated by exercise in the liver was found in the mitogen-activated protein kinase (MAPK) signalling pathway, with a pronounced and transient upregulation of the transcription factors encoded by c-Fos (also known as Fos), c-Jun (also known as Jun), FosB (also known as Fosb) and JunB (also known as Junb) and phosphorylation of hepatic MAPK. Acute exercise also activated the p53 signalling pathway. A major role for oxidative stress is unlikely since the antioxidant-enriched diet did not prevent the activation of the MAPK pathway. In contrast, lower plasma glucose levels after running were related to enhanced levels of MAPK signalling proteins, similar to the upregulation of Igfbp1 and Pgc-1alpha (also known as Ppargc1a). In the working muscle the activation of the MAPK pathway was weak and not related to plasma glucose concentrations. CONCLUSIONS/INTERPRETATION: Metabolic stress evidenced as low plasma glucose levels appears to be an important determinant for the activation of the MAPK signalling pathway and the transcriptional response of the liver to acute exercise.

Selective association of plasma non-esterified fatty acid species with circulating interleukin-8 concentrations in humans.

Elevated plasma concentrations of non-esterified fatty acids (NEFA), due to high fat intake and/or adipose tissue lipolysis, are a hallmark of the metabolic syndrome. We assessed whether certain plasma NEFA species contribute to the chronic low-grade inflammatory state seen in the metabolic syndrome. We determined the fasting plasma NEFA patterns of 75 overweight non-diabetic subjects and analysed their relationship with plasma inflammatory parameters. After adjustment for gender, age, body fat, and waist-hip ratio, no strong correlations of single NEFA species with leukocyte number, C-reactive protein, interleukin-6, tumour necrosis factor-alpha, or monocyte chemoattractant protein-1 were detected. However, oleate was negatively (r=-0.36, p=0.0015) and myristate (r=0.41, p=0.0003) as well as the omega3-polyunsaturated NEFA alpha-linolenate (r=0.37, p=0.0011), eicosapentaenoate (r=0.40, p=0.0003), and docosahexaenoate (r=0.40, p=0.0004) were positively associated with interleukin-8 concentrations. The other NEFA species as well as the total plasma NEFA concentration did not correlate with interleukin-8. The correlations of myristate, oleate, and the sum of all omega3-polyunsaturated NEFA with interleukin-8 were independent of plasma tumour necrosis factor-alpha and overall adiposity. Our data demonstrate close and selective associations of oleate, myristate, and omega3-polyunsaturated NEFA with plasma concentrations of the pro-inflammatory chemokine interleukin-8. Thus, these NEFA species may represent specific determinants of plasma interleukin-8.

Low hepatic stearoyl-CoA desaturase 1 activity is associated with fatty liver and insulin resistance in obese humans.

AIMS/HYPOTHESIS: Stearoyl-CoA desaturase 1 (SCD1) is the rate-limiting enzyme in monounsaturated fatty acid synthesis. It is imperative for the assembly of VLDL particles, which transport triacylglycerol (TG) from liver to adipose tissue and other sites. We aimed to determine the role of hepatic SCD1 activity in human glucose and lipid metabolism. METHODS: We studied 54 people participating in a lifestyle intervention programme with diet modification and increased physical activity. Insulin sensitivity was determined during a euglycaemic-hyperinsulinaemic clamp and estimated from an OGTT. Liver fat was quantified by (1)H-magnetic resonance spectroscopy at baseline and after 9 months of intervention. The pattern of fatty acids in serum VLDL-TGs was determined by ultracentrifugation followed by thin layer and gas chromatography, with the 18:1 n-9: 18:0 ratio providing an index of hepatic SCD1 activity. RESULTS: The hepatic SCD1 activity index correlated negatively with liver fat (r= -0.29, p=0.04) and positively with insulin sensitivity, both OGTT-derived (r=0.42, p=0.003) and clamp-derived (r=0.27, p=0.07). These correlations depended on overall adiposity. They were absent in leaner participants (n=27, liver fat: p=0.34, insulin sensitivity [OGTT]: p=0.75, insulin sensitivity [clamp]: p=0.24), but were strong in obese individuals (n=27, p=0.004, p=0.0002 and p=0.006, respectively). Furthermore, during intervention a high SCD1 activity index at baseline predicted a decrease in liver fat only in obese participants (r= -0.46, p=0.02). CONCLUSIONS/INTERPRETATION: Our data suggest that high hepatic SCD1 activity may regulate fat accumulation in the liver and possibly protects from insulin resistance in obesity.

High resolution gamma ray tomography scanner for flow measurement and non-destructive testing applications.

We report on the development of a high resolution gamma ray tomography scanner that is operated with a Cs-137 isotopic source at 662 keV gamma photon energy and achieves a spatial image resolution of 0.2 line pairs/ mm at 10% modulation transfer function for noncollimated detectors. It is primarily intended for the scientific study of flow regimes and phase fraction distributions in fuel element assemblies, chemical reactors, pipelines, and hydrodynamic machines. Furthermore, it is applicable to nondestructive testing of larger radiologically dense objects. The radiation detector is based on advanced avalanche photodiode technology in conjunction with lutetium yttrium orthosilicate scintillation crystals. The detector arc comprises 320 single detector elements which are operated in pulse counting mode. For measurements at fixed vessels or plant components, we built a computed tomography scanner gantry that comprises rotational and translational stages, power supply via slip rings, and data communication to the measurement personal computer via wireless local area network.

Oxidative stress, AGE, and atherosclerosis.

Numerous reports on the molecular mechanism of atherogenesis indicate an increase in oxidative stress, formation of advanced glycoxidation end products (AGEs), chronic inflammation, and activated cellular response particularly in diabetic patients. To elucidate the initiating and early accelerating events this review will focus on the molecular causes of the induction of these stress factors, their interactions, and their contribution to atherogenesis. Metabolic factors such as elevated free fatty acids, high glucose levels or AGEs induce reactive oxygen species (ROS) in vascular cells leading to ongoing AGE formation and to gene induction of proinflammatory cytokines. Vice versa, numerous cytokines found elevated in obesity and diabetes may also induce oxidative stress thus a circulus vitious may be initiated and accelerated. Increased production of ROS, mainly from mitochondria and NAD(P)H oxidase, stimulates signaling cascades including protein kinase C and mitogen-activated protein kinase pathway leading to nuclear translocation of transcription factors such as nuclear factor-kappaB (NF-kappaB), activator protein 1, and specificity protein 1. Subsequently, the expression of numerous genes including cytokines is rapidly induced, which, in turn, may act on vascular cells promoting the deleterious effects. From animal models of accelerated atherosclerosis a causal role of NAD(P)H oxidase and the AGE/RAGE/NF-kappaB axis to atherogenesis is suggested. Because all factors involved form a highly interwoven network of interactions, the blockade of ROS or AGE formation at different sites may interrupt the vicious cycle. Promising candidate agents are, currently on trial. Most important to clinical practice, a number of drugs commonly used in the treatment of diabetes, hypertension, or cardiovascular disease, such as angiotensin-converting enzyme inhibitors, AT(1) receptor blockers, 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins), and thiazolidindiones have shown promising 'preventive' intracellular antioxidant activity in addition to their primary pharmacological actions.

[Bilateral nasal remission spectroscopy allows the side separated continuous measurement of changes in swelling of the nasal mucosa]. / Schwellungsänderungen in der Nase: Die bilaterale nasale Remissionsspektroskopie zum seitengetrennten Echtzeit-Monitoring.

INTRODUCTION: In earlier studies optical transmission spectroscopy showed that continuous monitoring of changes in the swelling of the nasal mucosa is possible. However, independent measurement in both sides of the nose cannot be achieved by this method. With the aim of achieving real-time monitoring of endonasal swelling separately for both nostrils we developed the new method of bilateral nasal remission spectroscopy for this pilot study. MATERIALS AND METHODS: In nasal remission spectroscopy, light at a wavelength of 790 nm (close to the isobestic point of hemoglobin) is beamed into each side of the nose, and the light that is backscattered by the internal nasal tissue is measured continuously on the same nasal side. To evaluate the principle of this new method a pilot study was conducted in five healthy probands subjected to a one-sided (unilateral) nasal histamine provocation test (0.14 ml, 2 mg/ml). RESULTS: In each proband single-sided nasal histamine provocation led to an increase in light extinction on the provoked side by an average of 0.18 optical densities (OD). In four of the five probands a slight increase (0.04 OD) in light extinction was observed on the other side of the nose. CONCLUSION: Nasal remission spectroscopy seems to allow single-side, continuous monitoring on both sides of the nose. Therefore, the method could also be suitable for use in studies of the nasal cycle, as well as for objectivisation of nasal allergen provocation tests.