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BACKGROUND & AIMS: Previous investigations have aimed at investigating parameters affecting age perception on several ethnicities. Perceived health has been a newer focus on Caucasian skin, yet little is known on the skin features used to estimate the health status of Chinese women and we aimed to investigate whether these cues are the same as those used for age perception. METHODS: Age and health appearance of 276 Chinese female volunteers were estimated from their photographs by 1025 female naïve Chinese graders 20-69 years old. Models were built to predict perceived age and health from topographic, colour and biophysical measured variables, in two subsets of the studied volunteers: below and above 50 years. Machine learning-based predictive models for age and health perception were built on the collected data, and the interpretability of the models was established by measuring feature importance. RESULTS: Age perception was mostly driven by topographic features, particularly eye bags and eyelid sagging in the group below 50 years old. Wrinkles, notably from the lower part of the face and oval of the lower face, were found to be more relevant in the group above 50 years. Health appearance was primarily signalled by skin imperfections and global pigmentation in the subset below 50 years, whereas colour-related parameters and skin hydration acted as health cues for the subset above 50 years. CONCLUSION: Distinct skin features were acting as cues for age perception and/or health perception and varied per age subset. Their contribution should be borne in mind when designing products for 'younger looking skin' and 'healthier looking skin'.

OBJECTIF: Des études se sont penchées sur les paramètres cutanés influant sur la perception de l'âge, et ce sur plusieurs groups ethniques. La santé perçue quant à elle est un focus plus récent, avec des données publiées sur les peaux caucasiennes, au contraire des peaux chinoises. Nous avons donc décidé d'étudier quels sont ces paramètres cutanés influant sur la santé perçue et s'ils diffèrent de ceux utilisés dans la perception de l'âge, au sein d'un panel de femmes chinoises. MÉTHODES: L'âge et la santé cutanée de 276 femmes chinoises ont été estimés à partir de leurs photographies par un panel de 1025 évaluatrices naïves âgées de 20 à 69 ans. Des modèles ont été construits pour prédire l'âge et la santé perçus à partir de paramètres cutanés topographiques, de couleur et biophysiques, dans deux groupes d'âges différents : en dessous et au-dessus de 50 ans. Des modèles prédictifs basés sur l'apprentissage automatique (Machine learning) pour la perception de l'âge et de la santé ont été construits à partir des données collectées et l'interprétabilité des modèles a été établie en mesurant l'importance des paramètres cutanés. RÉSULTATS: Nos résultats montrent que la perception de l'âge repose principalement sur des paramètres topographiques, en particulier les poches sous les yeux et l'affaissement de la paupière, pour le groupe âgé de moins de 50 ans. Les rides, notamment celles de la partie basse du visage et le contour de la partie basse du visage se sont montrés pertinents pour estimer l'âge dans le groupe âgé de plus de 50 ans. La perception de la santé est principalement affectée par les imperfections cutanées et la pigmentation dans le groupe âgé de moins de 50 ans, tandis que des paramètres liés à la couleur et l'hydratation prennent le relais pour le groupe âgé de plus de 50 ans. CONCLUSION: Des paramètres cutanés de nature diverse sont pris en compte selon que l'on essaye d'estimer l'âge ou la santé, et ce en fonction du groupe d'âge étudié. Leur contribution doit être prise en compte lors de la conception de produits pour une «peau d'apparence plus jeune¼ et une «peau d'apparence plus saine¼.

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The purine nucleoside adenosine is clinically employed in the treatment of supraventricular tachycardia. In addition, it has direct coronary vasodilatory effects, and may influence platelet aggregation. Experimental observations mechanistically link extracellular adenosine to cellular adaptation to hypoxia. Adenosine generation has been implicated in several pathophysiologic processes including angiogenesis, tumor defenses and neurodegeneration. In solid organ transplantation, prolonged tissue ischemia and subsequent reperfusion injury may lead to profound graft dysfunction. Importantly, conditions of limited oxygen availability are associated with increased production of extracellular adenosine and subsequent tissue protection. Within the rapidly expanding field of adenosine biology, several enzymatic steps in adenosine production have been characterized and multiple receptor subtypes have been identified. In this review, we briefly examine the biologic steps involved in adenosine generation and chronicle the current state of adenosine signaling in hepatic ischemia and reperfusion injury.

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It has been hypothesized that autacoids, such as endothelin-1 (ET), may modulate erythropoietin (Epo) secretion. Therefore, we studied the effect of ET-1 infusion and of a nonselective ET(A/B) receptor antagonist on Epo secretion under carbon monoxide (CO) exposure. Anesthetized rats were supplied with room temperature air containing increasing concentrations of CO by an aerating cap. A CO-Epo dose-response curve over the range of 0.02-0.14 vol% CO was conducted. Subpressor doses of ET-1 (3 pmol/min/kg BW) and the ET(A/B) receptor antagonist LU302872 (LU; 30 mg/kg) were applied to anaesthetized rats under normoxia (controls CON, ET, LU) and following hypoxia (CO exposure; H-CON, H-ET, H-LU). Mean arterial blood pressure (MAP), glomerular filtration rate (GFR, inulin clearance), Epo and ET-1 serum concentrations (ELISA) and renal Epo mRNA (Light Cycler) were determined. The EC50 value for CO was 0.1 vol% with a 70-fold increase in Epo serum concentrations. CO exposure increased Epo serum and Epo mRNA concentrations in the expected range in all groups. None of the treatments with ET or LU influenced the effect of hypoxia on Epo serum concentrations and renal Epo mRNA content. Under hypoxia, administration of ET-1 as well as LU prevented the hypoxia-induced decrease in MAP (p<0.05). Under hypoxia, GFR was reduced by 50% except for H-LU with values comparable to normoxia. Taken together, the influence of hypoxia exceeds by far the effect of ET-1 on Epo production, irrespective of the presence or absence of exogenous ET-1. Thus, ET-1 does not appear to be a major modulator of Epo production.

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BACKGROUND: Cystatin C has recently been proposed as an ideal marker for glomerular filtration rate (GFR). In this study, cystatin C serum levels were evaluated in comparison to serum creatinine concentrations and inulin clearances in patients with normal kidney function receiving cisplatin-based chemotherapy to assess the validity of cystatin C as an alternative endogenous marker of GFR. METHODS: Blood samples for the assessment of cystatin C, creatinine and inulin clearances were collected in patients before and after application of cisplatin in a clinical trial. Overall, 41 patients were included in the study, 35 of them were eligible receiving cisplatin in two different cisplatin-based chemotherapy schedules. RESULTS: A 21% increase of cystatin C serum levels was demonstrated in the placebo group after application of cisplatin. Analysis of inulin clearances revealed a 23% loss of inulin clearance in patients of the placebo arm. In contrast, significant changes could not be detected by analysis of serum creatinine levels. CONCLUSIONS: Cystatin C represents a more sensitive clinical marker than serum creatinine for the early assessment of GFR damage caused by cisplatin. Changes in cystatin C serum concentrations correlate well to GFR decrease as measured by inulin clearance.

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Homocysteine is a precursor of S-adenosylmethionine (AdoMet) and a metabolite of S-adenosylhomocysteine (AdoHcy). The ratio of AdoMet to AdoHcy, defined as the methylation potential (MP), indicates the flow of methyl groups within the cells. Chronic elevations of total homocysteine (tHcy) in plasma correlate with increased AdoHcy concentrations, decreased MP, and impaired DNA methylation. However, the influence of acute hyperhomocysteinemia on MP is unknown. We induced acute hyperhomocysteinemia in 14 healthy volunteers by oral administration of l-homocysteine (65.1 micromol/kg body wt) in an open, randomized, placebo-controlled two-period crossover study. The kinetics of tHcy in blood and urine, MP in blood, and global DNA methylation in lymphocytes were studied systematically during 48 h. Plasma tHcy concentrations reached a peak at 34 +/- 11 min after an oral load with l-homocysteine and decreased with a half-life of 257 +/- 41 min (means +/- SD). Only 2.3% of the homocysteine dose were recovered in urine. AdoHcy concentrations and MP in whole blood and erythrocytes were not affected by the oral homocysteine load. Furthermore, global DNA methylation in lymphocytes did not change under these conditions. We found no difference between the genotypes of 5,10-methylenetetrahydrofolate reductase in response to the homocysteine load. However, AdoMet content in erythrocytes was significantly higher in the C677T carriers (CT; n = 7) compared with the CC genotype (n = 7). Although chronic elevation of tHcy has been shown to affect MP and DNA methylation, acute elevation of plasma tHcy above 20 micromol/l for 8 h is not sufficient to change MP and to induce DNA hypomethylation in lymphocytes.

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AIMS: Recent evidence suggests a potential role of angiotensin II in the physiological regulation of erythropoietin (Epo) production. While the administration of exogenous angiotensin II (AII) has been used so far to study its effects, the role of endogenous AII has remained unclear. METHODS: To alter endogenous AII in humans experimentally we used furosemide bolus injection as a short-term (study 1) and dietary salt as a long-term modulator (study 2). In an open crossover design, 12 healthy male volunteers received furosemide (F) 0.5 mg kg(-1) intravenously or placebo (P) in random order (study 1). With the same design, 12 volunteers received high-salt (HS), normal-salt (NS) and low-salt (LS) diet (study 2). Plasma renin activity (PRA) was analysed along with AII. Inulin and paraaminohippurate (PAH) clearances were used to indicate glomerular filtration rate (GFR) and renal plasma flow (RPF), respectively. RESULTS: While F stimulated AII and PRA and decreased GFR and RPF significantly, no concomitant alteration of Epo was observed [AUCEpo: placebo 5709 +/- 243 (% of baseline x h), furosemide: 5833 +/- 255 (% of baseline x h); 95% confidence interval (CI) -608.4, 856.0; P = 0.73]. F decreased GFR (from 103.6 +/- 4.0 to 90.6 +/- 4.8 ml min(-1) 1(-1) 73 m-2; 95% CI 1.1, 24.9; P < 0.05), but not RPF (study 1). Correspondingly, LS stimulated and HS decreased AII and PRA significantly. HS increased GFR and RPF. Again, Epo concentrations were not affected (AUCEpo: normal sodium 44 +/- 6.7 mIU x day ml(-1), low sodium 39 +/- 2.4 mIU x day ml(-1), high sodium 48.5 +/- 6.1 mIU x day ml(-1); normal salt/low salt 95% CI -11.9, 21.9, P = 0.54; normal salt/high salt 95% CI -14.4, 23.3, P = 0.63; study 2). CONCLUSIONS: We conclude that, at least in the physiological setting in healthy volunteers, increased concentrations of endogenous AII may not be a major factor of Epo regulation.

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New polymers containing 1,4,7-triazacyclononanes have been synthesised by means of ring opening metathesis polymerisation (ROMP); their complexes with Mn(II) catalyse the oxidation of simple olefins by hydrogen peroxide.

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Tumour necrosis factor-alpha (TNF-alpha) plays a pivotal role in the immune response and mediates inflammation by its receptors (TNF-RI and TNF-RII), as observed during rejection episodes and impaired graft function after liver transplantation. TNF-alpha and its receptors were analysed by an ELISA technique in serum samples from 77 consecutive liver transplantations in 63 patients. Samples were collected preoperatively from donors and recipients and then daily in the first two postoperative weeks. Peak levels of TNF-alpha and its soluble receptors (sTNF-RI and sTNF-RII) in the first and second postoperative week correlated with the extent of reperfusion injury. Impaired graft functions correlated with high sTNF-RI levels preoperatively (> 5 ng/ml, p = 0.01) and in the postoperative period (> 16 ng/ml, p = 0.02). Significantly increased TNF-alpha (> 25 pg/ml, p = 0.009) and sTNF-RI levels (> 5 ng/ml, p = 0.05) were found in donors of grafts with a high rejection risk. Elevated levels of TNF-alpha in the postoperative period correlated with an increased rejection risk (> 90 pg/ml, p = 0.02). The activity of the immune system with high concentrations of TNF-alpha and its receptors both in the recipient and the transplant donor seems to play an essential role in allograft development.

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BACKGROUND: The influence of DNA content on the prognosis in stomach cancer is controversial. METHOD: After curative resection of stomach carcinomas (adenocarcinomas [n = 58]; signet ring cell carcinomas [n = 24]; undifferentiated carcinomas [n = 21]), the influence of the DNA content and histomorphologic parameters on the prognosis was examined. RESULTS: In the multivariate regression analysis, the prognosis depended on the lymph node status (P = 0.0009), pT stage (P = 0.02), tumor localization (P = 0.03), and histologic type (P = 0.05). The prognosis was independent of the DNA content. Furthermore, the degree of differentiation, operative procedure, safety distance, size of the tumor, and sex and age of the patient also did not influence the prognosis. CONCLUSIONS: The DNA content of the tumor cells in stomach carcinoma does not influence prognosis.

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After curative resection of stomach carcinomas (adenocarcinomas: n = 58, signet ring cell carcinomas: n = 24, undifferentiated carcinomas: n = 21) the DNA content of the tumor cells was compared with the histomorphological parameters. There was a correlation between the DNA content and the histomorphological parameters. The DNA analysis had no additionally prognostic influence. In the multivariate regression analysis the prognosis depended on lymph node status (p = 0.0009), pT-stage (p = 0.02), tumor localization (p = 0.03) and the histological type (p = 0.05). The prognosis was independent of the DNA content. Furthermore, neither did the degree of differentiation, the operative procedure, the safety distance, the size of the tumor, the sex nor the age of the patient have any influence on the prognosis.

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