Body mass index, chronological age and hormonal status are better predictors of biological skin age than arm skin autofluorescence in healthy women who have never smoked.

BACKGROUND: As life expectancy is increasing and healthy ageing becomes more and more important, skin ageing is a growing topic of interest from both a medical and a commercial point of view. The urgency to unravel the causes of skin ageing is rising. However, there is a lack of objective, simple, noninvasive methods to assess biological skin age - a term introduced to describe how old someone looks, covering both the appearance and function of the skin. A rapid, noninvasive assessment of biological skin age would greatly facilitate the execution of the studies required to find the causes of skin ageing. OBJECTIVES: To find an objective, easy-to-apply method to assess biological skin age. METHODS: Skin age score (SAS) was compared with skin autofluorescence, a measure of advanced glycation end products in the skin, and several subject characteristics in 32 healthy, white women with little sun-exposed skin and no history of smoking. RESULTS: A moderate, positive correlation (R(2) = 0·32, P = 0·001) between SAS and skin autofluorescence-based biological skin age was found. However, the variation in biological skin age according to SAS could be explained better by body mass index, chronological age and hormonal status (R(2) = 0·86, P < 0·001). CONCLUSIONS: In the current setting skin autofluorescence did not contribute better to the prediction of biological skin age than chronological age. Biological skin age was best predicted by body mass index, chronological age and hormonal status, and this approach provides a considerable simplification of the application of biological skin age.

Reference values for the Chinese population of skin autofluorescence as a marker of advanced glycation end products accumulated in tissue.

AIM: Advanced glycation end products play an important role in the pathophysiology of several chronic and age-related diseases, especially diabetes mellitus. Skin autofluorescence is a non-invasive method for assessing levels of tissue advanced glycation end products. This study aims to establish the normal reference value of advanced glycation end products accumulated in tissue measured by the advanced glycation end product reader--skin autofluorescence--and discusses some factors influencing it. METHODS: The values of autofluorescence in healthy individuals in China were determined by the advanced glycation end product reader; age, gender, skin reflectance, smoking habits and alcohol consumption of the subjects were also recorded. RESULTS: The mean reference values of autofluorescence in healthy Chinese subjects are (95% confidence interval) 20-29 years: 1.54-1.62 arbitrary units; 30-39 years: 1.66-1.75; 40-49 years: 1.78-1.89; 50-59 years: 1.87-2.03; 60-69 years: 1.86-2.09; 70-79 years: 1.97-2.31. The value of autofluorescence is strongly related to age, but no significant difference between males and females were found (all P > 0.05). Autofluorescence was higher in smokers than in non-smokers (P < 0.05). In persons with low skin reflectance (< 10%), skin autofluorescence was dependent on skin colour, but was still related to age. CONCLUSIONS: The mean reference values of autofluorescence we established could be used for a Chinese population in a clinical setting and are agreement with those in a Caucasian population. Future developments are needed to make the advanced glycation end product reader reliable for lower skin reflections as well, independently of the skin colour.

Skin autofluorescence provides additional information to the UK Prospective Diabetes Study (UKPDS) risk score for the estimation of cardiovascular prognosis in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: The UK Prospective Diabetes Study (UKPDS) risk engine has become a standard for cardiovascular risk assessment in type 2 diabetes mellitus. Skin autofluorescence was recently introduced as an alternative tool for cardiovascular risk assessment in diabetes. We investigated the prognostic value of skin autofluorescence for cardiovascular events in combination with the UKPDS risk engine in a cohort of patients with type 2 diabetes managed in primary care. METHODS: Clinical, UKPDS risk engine and skin autofluorescence data were obtained at baseline in 2001-2002 in the type 2 diabetes group (n = 973). Follow-up data concerning fatal and non-fatal cardiovascular events (primary endpoint) were obtained till 2005. Patients were classified as 'low risk' when their 10 year UKPDS risk score for fatal cardiovascular events was <10%, and 'high risk' if >10%. Skin autofluorescence was measured non-invasively with an autofluorescence reader. Skin autofluorescence was classified by the median (i.e. low risk < median, high risk > median). RESULTS: The incidence of cardiovascular events was 119 (44 fatal, 75 non-fatal). In multivariate analysis, skin autofluorescence, age, sex and diabetes duration were predictors for the primary endpoint. Addition of skin autofluorescence information to that from the UKPDS risk engine resulted in re-classification of 55 of 203 patients from the low-risk to the high-risk group. The 10 year cardiovascular event rate was higher in patients with a UKPDS score >10% when skin autofluorescence was above the median (55.8% vs 38.9%). CONCLUSIONS/INTERPRETATION: Skin autofluorescence provides additional information to the UKPDS risk engine which can result in risk re-classification of a substantial number of patients. It furthermore identifies patients who have a particularly high risk for developing cardiovascular events.

Skin autofluorescence for the risk assessment of chronic complications in diabetes: a broad excitation range is sufficient.

Skin autofluorescence (AF) is becoming an accepted clinical method for assessing the risk of chronic complications in diabetes mellitus (DM). In this study, the role of the excitation wavelength in the recognition of increased risk of diabetes-related chronic complications was investigated. An Excitation Emission Matrix Scanner (EEMS) was used to perform noninvasive measurements in four age-matched groups of patients with type 1 and type 2 DM, with and without chronic complications, as well as in a control group (N=97 in total). AF was calculated for excitation wavelengths in the range 355 - 405 nm. Mean spectra were assessed per group. AF values in both type 1 and type 2 DM patients with complications were increased compared to the control subjects (p < 0:01); this ratio remained practically constant, independent of the excitation wavelength. No emission peaks were distinctive for specific patient groups. We conclude that in these groups, no characteristic fluorophores dictate the use of a specific wavelength or set of wavelengths. The results show the validity of applying a broad excitation wavelength range for risk assessment of chronic complications in diabetes.

Skin autofluorescence is elevated in acute myocardial infarction and is associated with the one-year incidence of major adverse cardiac events.

BACKGROUND.: ST-elevation myocardial infarction (STEMI) is associated with increased inflammation and oxidative stress, enhancing the formation of advanced glycation endproducts (AGEs). These encompass a characteristic fluorescence pattern, which can be non-invasively measured as skin autofluorescence (AF). In this study we investigate whether skin AF is elevated in STEMI, its association with inflammatory and glycaemic stress and its predictive value for future events. METHODS.: Skin AF was measured in 88 STEMI patients (mean age 64+/-13 years) within 72 hours and around six months after discharge, in 81 stable coronary artery disease (sCAD) patients (64+/-10 years), and in 32 healthy controls (63+/-11 years). The cumulative one-year incidence of all-cause mortality and hospitalisation for myocardial infarction or heart failure was documented. RESULTS.: Skin AF was significantly higher in STEMI compared with sCAD and controls, irrespective of confounders, and was associated with HbA1c and C-reactive protein. Skin AF decreased significantly in STEMI patients, when measured >200 days after discharge. In STEMI patients, skin AF above the median was predictive of future events (hazard ratio 11.6, 95% CI 1.5 to 90.8, p=0.019). CONCLUSION.: Skin AF is elevated in STEMI, is associated with inflammation and glycaemic stress, and predicts future major adverse cardiac events. (Neth Heart J 2009;17:162-8.Neth Heart J 2009;17:162-8.).

Skin autofluorescence is increased in systemic lupus erythematosus but is not reflected by elevated plasma levels of advanced glycation endproducts.

OBJECTIVES: To examine whether skin advanced glycation endproducts (AGEs) accumulation, plasma levels of AGEs-N(epsilon)-carboxymethyllysine (CML) and N(epsilon)-carboxyethyllysine (CEL)-and serum levels of soluble receptor for AGEs (sRAGE) are elevated in SLE patients compared with controls, and whether these parameters are related to disease activity and endothelial cell (EC) activation. METHODS: Ten SLE patients (9 women, age 34 +/- 13 yrs, mean +/- s.d.) and 10 age- and sex-matched controls were included. Patients were analysed during inactive as well as active disease. Skin AGE accumulation was estimated using ultraviolet-A (UV-A) light for measurement of autofluorescence obtained by Excitation-Emission matrix Scanner (AF-EEMS). Levels of CML and CEL were determined by tandem mass spectrometry. Levels of sRAGE and of soluble vascular cell adhesion molecule-1 (sVCAM-1) were determined by ELISAs. RESULTS: Skin AF-EEMS was increased in SLE patients compared with controls (P < 0.05). Levels of CML and CEL were comparable between patients and controls and were not influenced by disease activity. sRAGE and sVCAM-1 levels were higher in quiescent SLE patients compared with controls (P < 0.05) and increased further during active disease (P < 0.05). In patients with quiescent disease and controls, sRAGE levels correlated to sVCAM-1 levels (r = 0.579, P = 0.007). CONCLUSIONS: Skin AGEs and levels of sRAGE and sVCAM-1 were elevated in SLE patients, whereas levels of CML and CEL were comparable with controls. As sRAGE even further increased during endothelial activation, it might be hypothesized that sRAGE acts as a decoy receptor. Why this proposed mechanism is insufficient to prevent increased AGE accumulation in the skin of SLE patients has to be established.

Advanced glycation end products and the absence of premature atherosclerosis in glycogen storage disease Ia.

INTRODUCTION: Despite their unfavourable cardiovascular risk profile, patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis. We hypothesized that this paradox might be related to a decreased formation of advanced glycation end products (AGEs) resulting from lifetime low plasma glucose levels and decreased oxidative stress. METHODS: In 8 GSD Ia patients (age 20-34 years) and 30 matched controls we measured carotid intima-media thickness (IMT), skin autofluorescence (AF; a non-invasive index for AGEs), and specific AGEs (pentosidine, N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL)) and collagen linked fluorescence (CLF, measured at excitation/emission wavelength combinations of 328/378 and 370/440 nm) in skin samples. RESULTS: Carotid IMT was significantly lower in GSD Ia patients. Skin AF did not differ between patients and controls. The skin samples showed higher CEL levels in the patient group (p = 0.008), but similar levels of pentosidine, CML, and CLF. In the total group, skin AF correlated with CML (r = 0.39, p = 0.031), CLF 328/378 nm (r = 0.53; p = 0.002) and CLF 370/440 nm (r = 0.60; p = 0.001). In the control group, AF also correlated with the maximum carotid IMT (r = 0.6; p = 0.004). CONCLUSION: Although our data confirm that GSD Ia patients present with a reduced burden of atherosclerosis, this phenomenon cannot be explained by differences in AGE accumulation as measured in the skin.

New developments in phase refinement.

A longstanding problem in X-ray crystallography is that vital information regarding the crystal phases in missing from the experimental data that are gathered in the diffraction experiment. Prior knowledge needs to be introduced in order to resolve phase ambiguities whenever the diffraction data are not sufficient to unequivocally reconstruct the crystal phases through anomalous or isomorphous differences. Very recent developments include progress in the application of direct methods to small proteins and other compounds of a similar small size (Shake 'n' Bake, SHELXD, CRUNCH and SIR96), bias-free refinement through the gamma-correction (Solomon), improvements in the determination of phase probability distributions (SHARP) and automated atomic refinement (wARP).

Influence of hemodilution of plasma proteins on erythrocyte aggregability: an in vivo study in patients undergoing cardiopulmonary bypass.

Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB) surgery. Blood samples were taken before, during, and after operation from 40 coronary artery bypass grafting patients who were operated with CPB and concomitant hemodilution (CPB, n=20) and who without (nonCPB, n=20). Erythrocyte aggregation was determined with a LORCA aggregometer, during which all samples were standardized to a hematocrit level of 40%. Results showed that in the CPB patients the aggregation index (AI) dropped to 44% of its preoperative baseline level 5 minutes after the start of hemodilution (from 47.7+/-10.1 to 26.6+/-11.4, p<0.01). Meanwhile, plasma concentration of fibrinogen (Fb) dropped to 55%, haptoglobin to 85%, ceruloplasmin to 55%, and albumin to 67%. In the nonCPB patients, however, there was only a slight drop in AI and the concentrations of plasma proteins during the similar period of time. On postoperative day 1, AI was rebounded to 37.1+/-12.4 in CPB patients compared with 44.3+/-11.7 in nonCPB patients. At baseline, AI was correlated only with Fb. During CPB and hemodilution, AI was correlated not only with Fb but also with haptoglobin and ceruloplasmin. Postoperatively, significant correlationship was found between AI and Fb, CRP, haptoglobin, ceruloplasmin, as well as albumin. These results indicate that hemodilution of plasma proteins significantly reduces the aggregability of erythrocytes in patients undergoing CPB. Besides Fb, other plasma proteins also contribute to AI during the early postoperative period when patients are recovering from CPB surgery.

The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients.

BACKGROUND/OBJECTIVES: The level of skin autofluorescence (AF) at a given moment is an independent predictor of mortality in hemodialysis (HD) patients. Skin AF is a measure of the accumulation of advanced glycation end products (AGEs). The aim of the study was to estimate the influence of nutrition on the 1-year increase of skin AF (ΔAF) in HD patients. SUBJECTS/METHODS: A total of 156 HD patients were enrolled in this study. Skin AF, body mass index (BMI), superoxide dismutase, myeloperoxidase, C-reactive protein, inter-cellular adhesion molecule-1, von Willebrand factor and heart-type fatty acid-binding protein were measured four times at intervals of approximately half a year. Data from the monthly routine blood analysis were also used. Daily calorie, protein and AGE intakes were assessed from food recordings over a period of 1 week. RESULTS: A J-shaped relation was found between baseline BMI and ΔAF (P=0.01). The lowest point of the J-shaped curve is found for BMI=24.3 kg/m(2). In the univariate analysis of the contributors to the 1-year ΔAF, we found that beside BMI=24.3 kg/m(2), AGE and calorie intakes, as well as myeloperoxidase and HD vintage, had a P <0.10. The sole independent predictor of the 1-year ΔAF was BMI=24.3 kg/m(2) (P=0.01). CONCLUSIONS: It appears that calorie, protein and AGE intakes hardly influence the 1-year ΔAF in HD patients. BMI of HD patients of around 24 kg/m(2) resulted in a lower 1-year ΔAF.

Corrigendum. The influence of body mass index on the accumulation of advanced glycation end products in hemodialysis patients.

Correction to: European Journal of Clinical Nutrition (2015) 69, 309­313; doi: 10.1038/ejcn.2014.261; published online 14 January 2015 Since the publication of this article, the authors have noticed that several of the author names were published incorrectly. The correct author names are listed above. The .html and online PDF versions have also been amended. The authors apologise for any inconvenience caused.

Digestion of so-called resistant starch sources in the human small intestine.

BACKGROUND: Resistant starch sources, which are only partially digested in the small intestine, can be used to increase colonic availability of short-chain fatty acids. OBJECTIVE: To study the characteristics of the fermentation of resistant starch, the digestion of resistant starch in the small intestine has to be quantified. We compared the metabolic fates of highly digestible cornstarch (DCS), Hylon VII (type 2 resistant starch), and Novelose 330 (type 3 resistant starch), which are of corn origin and, therefore, naturally enriched in (13)C. DESIGN: After administration of 40 g starch or glucose to 7 healthy volunteers, glucose and exogenous glucose concentrations in serum and (13)CO(2) excretion in breath were analyzed for 6 h. (13)C abundance in carbon dioxide was analyzed by isotope ratio mass spectrometry (IRMS) and (13)C abundance in glucose by gas chromatography-combustion IRMS. RESULTS: By comparing the area under the curve (2 h) of exogenous glucose concentration in serum ((13)C glycemic index) after intake of starch or glucose, (13)C glycemic indexes for DCS, Hylon VII, and Novelose 330 were calculated to be 82 +/- 23%, 44 +/- 16%, and 43 +/- 15%, respectively. Comparison of 6-h cumulative percentage dose recovery in breath showed that 119 +/- 28% of DCS, 55 +/- 23% of Hylon VII, and 50 +/- 26% of Novelose 330 was digested in the small intestine. CONCLUSION: The exogenous glucose response in serum and the (13)CO(2) excretion in breath can be used to estimate small intestinal digestion of resistant starch, which amounts to approximately 50%.

On the influence of flow conditions and wettability on blood material interactions.

In this review, we hypothesise that, next to biocompatibility, optimal blood compatibility depends on a combination of biomaterials wettability and the shear stress prevailing in the device. The wettability is discussed in seven different categories of devices, that differ substantially from each other with regard to shear stress and exposure time. These seven categories are stents, prosthetic heart valves, vascular prostheses, cardiopulmonary bypass, hemodialysis, vena cava filters and blood bags. In high shear applications, in combination with blood activation, platelet deposition and thrombosis appear to be major problems and platelet inhibitors are most effective. Exposure of blood to a large biomaterial surface, with or without antithrombotic coating, results in reduction of platelet function. Material-independent activation aggravates this process. In low shear applications, platelets only seem supportive for coagulation and anticoagulants should be used.

Practical improvements on photon diffusion theory: application to isotropic scattering.

Based on the analysis of an isotropic point source in an infinite, isotropically scattering turbid medium, we suggest several modifications to the well-known diffusion theory. Compared with standard diffusion theory these modifications, which require very little extra mathematics, lead to a substantially better approximation of the exact expressions. The improved expression gives reasons to reconsider the basic concept of time-resolved diffusion theory.

Aspects of similarity in tissue optics with strong forward scattering.

The similarity studied in this paper links the diffusion exponent to the reduced albedo. If F is the ratio of the diffusion exponent assumed by standard diffusion theory to the actual value of the diffusion exponent, it is shown that for forward-scattering functions, as often found in biological tissues, the values of F approach limiting curves. These curves depend on a constant in the homologous scattering patterns, which can describe Henyey-Greenstein scattering patterns, but which can also approximate Rayleigh-Gans phase functions. Finally, a practical approach for estimating the solution for mixtures of these forward-scattering phase functions with isotropic scatterers has been given.

A simple and accurate formula for the sound velocity in water.

The sound velocity in test objects and phantoms is often measured by performing a differential measurement with pure water. To promote standardization, a simple formula for the sound velocity in water is derived that renders true values within 0.20 m s(-1) over the temperature range 15-35 C. The formula is given by c = 1404.3 + 4.7 T - 0.04 T2, with sound velocity c in m s(-1) and temperature T in C.

A semiconductor laser used for direct measurement of the blood perfusion of tissue.

An instrument consisting merely of a semiconductor laser in its own housing was used to measure the blood perfusion in tissue. Use is made of the feedback of Doppler-scattered light to the photodiode in the laser housing. A recording perfusion of a finger under occlusion of blood flow in the arm is shown.

The conservative treatment of patients presenting with Grisel's syndrome.

Two cases of Grisel's syndrome are described to demonstrate that early recognition of this condition allows effective conservative treatment. To explain the good response to early conservative treatment, a combination of hypotheses is proposed.

Von Recklinghausen neurofibromatosis (VRNF) and pregnancy. A single case study.

A case of Von Recklinghausen neurofibromatosis (VRNF) with progression during two pregnancies and obstetrical complications is described to illustrate the effect of pregnancy on VRNF and vice versa. The interaction between VRNF and pregnancy is discussed. The obstetrical complications and progression of VRNF lesions during pregnancy necessitate close follow-up of these patients by neurologist and obstetrician.

Sciatic nerve compression by an aneurysm of the internal iliac artery.

A 73-year-old female with severe sciatica suffered from an aneurysm of the left internal iliac artery. At first minimal caudographic abnormalities suggested intervertebral disc herniation and lumbar root compression but at exploratory surgery the diagnosis had to be rejected. Once the correct diagnosis was established by echography, CT-scanning and angiography surgical treatment of the aneurysm resulted in complete recovery. Because sciatic nerve lesions due to aneurysms in the pelvic region very seldom occur and may be the cause of diagnostic confusion, symptoms and treatment of these aneurysms are discussed.