Effect of exogenous and endogenous ketones on respiratory exchange ratio and glucose metabolism in healthy subjects.

This study examined the effect of exogenous ketone bodies (KB) on oxygen consumption (V̇o2), carbon dioxide production (V̇co2), and glucose metabolism. The data were compared with the effects of endogenous ketonemia during both, a ketogenic diet or fasting. Eight healthy individuals [24.1 ± 2.5 yr, body mass index (BMI) 24.3 ± 3.1 kg/m2] participated in a crossover intervention study and were studied in a whole-room indirect calorimeter (WRIC) to assess macronutrient oxidation following four 24-h interventions: isocaloric controlled mixed diet (ISO), ISO supplemented with ketone salts (38.7 g of ß-hydroxybutyrate/day, EXO), isocaloric ketogenic diet (KETO), and total fasting (FAST). A physical activity level of 1.65 was obtained. In addition to plasma KB, 24-h C-peptide and KB excretion rates in the urine and postprandial glucose and insulin levels were measured. Although 24-h KB excretion increased in response to KETO and FAST, there was a modest increase in response to EXO only (P < 0.05). When compared with ISO, V̇o2 significantly increased in KETO (P < 0.01) and EXO (P < 0.001), whereas there was no difference in FAST. V̇co2 increased in EXO but decreased in KETO (both P < 0.01) and FAST (P < 0.001), resulting in 24-h respiratory exchange ratios (RER) of 0.828 ± 0.024 (ISO) and 0.811 ± 0.024 (EXO) (P < 0.05). In response to EXO there were no differences in basal and postprandial glucose and insulin levels, as well as in insulin sensitivity. When compared with ISO, EXO, and KETO, FAST increased homeostatic model assessment ß-cell function (HOMA-B) (all P < 0.05). In conclusion, at energy balance exogenous ketone salts decreased respiratory exchange ratio without affecting glucose tolerance.NEW & NOTEWORTHY Our findings revealed that during isocaloric nutrition, additional exogenous ketone salts increased V̇o2 and V̇co2 while lowering the respiratory exchange ratio (RER). Ketone salts had no effect on postprandial glucose metabolism.

Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants.

BACKGROUND & AIMS: Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as ß-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception. METHODS: Eight healthy young adults (4 women, 4 men, age 24 ± 3 years, BMI 24.3 ± 3.1 kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7 g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured. RESULTS: Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p > 0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110 ± 54 kcal/d vs. ISO, p < 0.05) and SEE (+201 ± 90 kcal/d vs. ISO, p < 0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48 ± 27 g/d, p < 0.05) resulting in a positive CHO balance (p < 0.05). No differences between the interventions were found for subjective appetite ratings (all p > 0.05). CONCLUSION: A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance. CLINICAL TRIAL REGISTRATION: NCT04490226 https://clinicaltrials.gov/.

Urinary Copper Excretion Is Associated with Long-Term Graft Failure in Kidney Transplant Recipients.

INTRODUCTION: In chronic kidney disease, proteinuria increases urinary copper excretion, inducing oxidative tubular damage and worsening kidney function. We investigated whether this phenomenon occurred in kidney transplant recipients (KTRs). In addition, we studied the associations of urinary copper excretion with the biomarker of oxidative tubular damage urinary liver-type fatty-acid binding protein (u-LFABP) and death-censored graft failure. METHODS: This prospective cohort study was performed in the Netherlands between 2008 and 2017, including outpatient KTR with a functioning graft for longer than 1 year, who were extensively phenotyped at baseline. Twenty-four-hour urinary copper excretion was measured by inductively coupled plasma mass spectrometry. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (57% men, 53 ± 13 years, estimated glomerular filtration rate [eGFR] 52 ± 20 mL/min/1.73 m2), baseline median urinary copper excretion was 23.6 (interquartile range 11.3-15.9) µg/24 h. Urinary protein excretion was positively associated with urinary copper excretion (standardized ß = 0.39, p < 0.001), and urinary copper excretion was positively associated with u-LFABP (standardized ß = 0.29, p < 0.001). During a median follow-up of 8 years, 109 (16%) KTR developed graft failure. KTR with relatively high copper excretion were at higher risk of long-term graft failure (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.32-1.86 per log2, p < 0.001), independent of multiple potential confounders like eGFR, urinary protein excretion, and time after transplantation. A dose-response relationship was observed over increasing tertiles of copper excretion (HR: 5.03, 95% CI: 2.75-9.19, tertile 3 vs. 1, p < 0.001). u-LFABP was a significant mediator of this association (74% of indirect effect, p < 0.001). CONCLUSION: In KTR, urinary protein excretion is positively correlated with urinary copper excretion. In turn, higher urinary copper excretion is associated with an independent increased risk of kidney graft failure, with a substantial mediating effect through oxidative tubular damage. Further studies are warranted to investigate whether copper excretion-targeted interventions could improve kidney graft survival.

Low selenium intake is associated with risk of all-cause mortality in kidney transplant recipients.

BACKGROUND: Deficiency of the essential trace element selenium is common in kidney transplant recipients (KTR), potentially hampering antioxidant and anti-inflammatory defence. Whether this impacts the long-term outcomes of KTR remains unknown. We investigated the association of urinary selenium excretion, a biomarker of selenium intake, with all-cause mortality; and its dietary determinants. METHODS: In this cohort study, outpatient KTR with a functioning graft for longer than 1 year were recruited (2008-11). Baseline 24-h urinary selenium excretion was measured by mass spectrometry. Diet was assessed by a 177-item food frequency questionnaire, and protein intake was calculated by the Maroni equation. Multivariable linear and Cox regression analyses were performed. RESULTS: In 693 KTR (43% men, 52 ± 12 years), baseline urinary selenium excretion was 18.8 (interquartile range 15.1-23.4) µg/24-h. During a median follow-up of 8 years, 229 (33%) KTR died. KTR in the first tertile of urinary selenium excretion, compared with those in the third, had over a 2-fold risk of all-cause mortality [hazard ratio 2.36 (95% confidence interval 1.70-3.28); P < .001], independent of multiple potential confounders including time since transplantation and plasma albumin concentration. The most important dietary determinant of urinary selenium excretion was protein intake (Standardized ß 0.49, P < .001). CONCLUSIONS: Relatively low selenium intake is associated with a higher risk of all-cause mortality in KTR. Dietary protein intake is its most important determinant. Further research is required to evaluate the potential benefit of accounting for selenium intake in the care of KTR, particularly among those with low protein intake.

Plasma Copper Concentration Is Associated with Cardiovascular Mortality in Male Kidney Transplant Recipients.

Kidney transplant recipients (KTR) are at increased risk of cardiovascular mortality. We investigated whether, in KTR, post-transplantation copper status is associated with the risk of cardiovascular mortality and potential effect modification by sex. In this cohort study, plasma copper was measured using mass spectrometry in extensively-phenotyped KTR with a functioning allograft >1-year. Cox regression analyses with the inclusion of multiplicative interaction terms were performed. In 660 KTR (53 ± 13 years old, 56% male), the median baseline plasma copper was 15.42 (IQR 13.53-17.63) µmol/L. During a median follow-up of 5 years, 141 KTR died, 53 (38%) due to cardiovascular causes. Higher plasma copper was associated with an increased risk of cardiovascular mortality in the overall KTR population (HR 1.37; 95% CI, 1.07-1.77 per 1-SD, p = 0.01). Sex was a significant effect modifier of this association (Pinteraction = 0.01). Among male KTR, higher plasma copper concentration was independently associated with a two-fold higher risk of cardiovascular mortality (HR 2.09; 95% CI, 1.42-3.07 per 1-SD, p < 0.001). Among female KTR, this association was absent. This evidence offers a rationale for considering a sex-specific assessment of copper's role in cardiovascular risk evaluation. Further studies are warranted to elucidate whether copper-targeted interventions may decrease cardiovascular mortality in male KTR.

Dietary lithium intake, graft failure and mortality in kidney transplant recipients.

BACKGROUND: Long-term high-dose lithium therapy in bipolar disorder is known to adversely affect kidney function. However, recent animal studies have revealed that low amounts of lithium are beneficial for the kidney when it is damaged by exposure to nephrotoxic compounds, inflammation or oxidative stress. This study aimed to investigate whether urinary lithium excretion, reflecting dietary lithium intake, is associated with adverse long-term kidney graft outcomes and patient survival. METHODS: Urinary lithium concentration was measured using inductively coupled plasma mass spectrometry in 642 stable kidney transplant recipients (KTRs). Graft failure was defined as the start of dialysis or retransplantation and kidney function decline was defined as a doubling of serum creatinine. RESULTS: The median urinary lithium excretion was 3.03 µmol/24 h [interquartile range (IQR) 2.31-4.01]. Urinary lithium excretion was associated with energy, plant protein and water intake. During a median follow-up of 5.3 years (IQR 4.5-6.0), 79 (12%) KTRs developed graft failure and 127 (20%) KTRs developed kidney function decline. Higher urinary lithium excretion was associated with a lower risk of graft failure {hazard ratio [HR] per doubling 0.54 [95% confidence interval (CI) 0.38-0.79]} and kidney function decline [HR per doubling 0.73 (95% CI 0.54-0.99)]. These associations remained independent of adjustment for potential confounders and in sensitivity analyses. There was a significant effect modification with the use of proliferation inhibitors (P = .05) and baseline estimated glomerular filtration rate (eGFR; P < .001), with higher urinary lithium excretion being more protective in KTRs not using proliferation inhibitors and in KTRs with lower baseline eGFR. Furthermore, higher urinary lithium excretion was associated with a reduced risk of all-cause mortality [HR 0.64 (95% CI 0.49-0.83); P = .001]. CONCLUSION: Dietary lithium intake may be a potentially modifiable, yet rather overlooked, risk factor for adverse long-term kidney graft outcomes and patient survival. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02811835.

Minerals and Trace Elements in 990 Beverages and Their Contribution to Dietary Reference Values for German Consumers.

Beverages are an integral part of human nutrition, yet little is known about their contribution to daily intakes of minerals and trace elements in German consumers. Using inductively coupled plasma-mass spectrometry, we determined the concentration of five minerals and six trace elements in beverage samples (n = 990, assigned to different beverage groups) collected throughout Germany. For a calculation of their relative contribution to the mineral supply, available beverage consumption data was combined with our quantitative analysis to calculate the average contribution of beverage groups to meet the respective dietary reference values currently used in Germany, Austria and Switzerland (D-A-CH region). Based on their presence in beverages and their consumption, the top three minerals are phosphorous, calcium and magnesium, and they, therefore, may reasonably contribute to the reference values. Among the trace elements, beverages mostly contributed to the manganese supply, whereas at the same time, concentrations of iron, cobalt and copper were low across all tested groups. Our study provides an overview of the assumed mineral and trace element intake via beverages in Germany and may, thus, serve as a foundation for a mineral and trace element database of beverages that needs to be expanded in the future.

Boron Intake and decreased risk of mortality in kidney transplant recipients.

PURPOSE: In a search for potentially modifiable factors to improve long-term outcome among kidney transplant recipients (KTR), we hypothesized that boron exposure is associated with improved long-term outcome in KTR. METHODS: We determined 24 h urinary boron excretion using inductively coupled plasma mass spectrometry as a measure of boron exposure in 693 stable KTR (57% male, mean age 53y), enrolled in the TransplantLines Food and Nutrition Biobank and Cohort Study. Dietary intake was assessed using validated food-frequency questionnaires. RESULTS: Linear regression analyses showed that dietary intake of fruit, wine and nuts were key determinants of boron excretion. In addition, boron excretion was negatively correlated with homocysteine and inflammatory parameters. In total, 73 (32%), 47 (20%) and 30 (13%) KTR died among the lowest, middle and highest tertiles of 24 h urinary boron excretion, respectively (Plog-rank < 0.001). Cox regression analyses showed that high boron excretion was strongly associated with lower risk of mortality, independent of age, sex, estimated glomerular filtration rate and history of cardiovascular disease (HR per doubling: 0.51, 95% CI: 0.40 to 0.66, P < 0.001). CONCLUSION: Boron may be an overlooked target to improve long-term survival among KTR and potentially other patients, likely through pathways other than inflammation or the methionine-homocysteine cycle that were previously suggested. Interventional trials are warranted to confirm the potential of dietary boron supplementation in KTR and other patient populations.

Plasma boron concentrations in the general population: a cross-sectional analysis of cardio-metabolic and dietary correlates.

PURPOSE: Experimental evidence suggests positive effects of boron on health and metabolism, but human data are still scarce. We aimed to identify dietary and cardio-metabolic correlates of plasma boron concentrations in the general population. METHODS: In a community-based sample (n = 899, 57% men, mean age 61 years), plasma boron (median [IQR]: 33.80 µg/L [25.61; 44.65]) concentrations were measured by inductively coupled plasma-mass spectrometry. Overall (PDI), healthy (hPDI), and unhealthy (uPDI) plant-based diet indices were derived from a validated food frequency questionnaire. Reduced rank regression (RRR) yielded a dietary pattern explaining 30% of the variation of circulating boron. Cross-sectional associations of dietary indices and cardio-metabolic traits with plasma boron concentrations were assessed using multivariable-adjusted linear regression analysis. RESULTS: The RRR pattern was characterized by high intake of fruits, nuts/seeds, tea, wine and low intake of e.g. bread, poultry, processed meat, chocolate/sweets, and soft drinks. 10-point increments in PDI, hPDI, and uPDI were associated with 8.7% (95% CI: 4.2; 13.4), 10.4% (95% CI: 6.6; 14.3), and -8.8% (95% CI: -12.1; -5.4) change in plasma boron concentrations, respectively. Age and phosphate were directly, while BMI, plasma lipid concentrations, and CRP were inversely associated with circulating boron. Plasma boron concentrations were higher in summer vs. winter, in individuals taking vs. not taking antihypertensive medication, and in individuals with high or medium vs. low education level. CONCLUSION: Higher plasma boron concentrations appeared to associate with a healthier diet, were related to lower BMI and a more favorable cardio-metabolic risk profile, and showed seasonal variations.

Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans.

SCOPE: Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined. METHODS AND RESULTS: Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L-1 ), medium (113.9 µg L-1 ), or high (2193.3 µg L-1 ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water. CONCLUSION: Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans.

Taurine Enhances Iron-Related Proteins and Reduces Lipid Peroxidation in Differentiated C2C12 Myotubes.

Taurine is a nonproteinogenic amino sulfonic acid in mammals. Interestingly, skeletal muscle is unable to synthesize taurine endogenously, and the processing of muscular taurine changes throughout ageing and under specific pathophysiological conditions, such as muscular dystrophy. Ageing and disease are also associated with altered iron metabolism, especially when there is an excess of labile iron. The present study addresses the question of whether taurine connects cytoprotective effects and redox homeostasis in a previously unknown iron-dependent manner. Using cultured differentiated C2C12 myotubes, the impact of taurine on markers of lipid peroxidation, redox-sensitive enzymes and iron-related proteins was studied. Significant increases in the heme protein myoglobin and the iron storage protein ferritin were observed in response to taurine treatment. Taurine supplementation reduced lipid peroxidation and BODIPY oxidation by ~60 and 25%, respectively. Furthermore, the mRNA levels of redox-sensitive heme oxygenase (Hmox1), catalase (Cat) and glutamate-cysteine ligase (Gclc) and the total cellular glutathione content were lower in taurine-supplemented cells than they were in the control cells. We suggest that taurine may inhibit the initiation and propagation of lipid peroxidation by lowering basal levels of cellular stress, perhaps through reduction of the cellular labile iron pool.

Plasma Lithium Levels in a General Population: A Cross-Sectional Analysis of Metabolic and Dietary Correlates.

Initial evidence suggests that lithium might affect life expectancy and the risk for different disease conditions, but most studies were conducted in patients on lithium medication. Little is known about the association of blood lithium levels within the physiological range with cardiometabolic risk factors and diet. We measured plasma lithium in a community-based sample from Northern Germany (samples taken between 2010 and 2012). All participants (aged 25-82 years) underwent standardized examinations and completed a semi-quantitative food frequency questionnaire. Of several variables tested, the estimated glomerular filtration rate (eGFR) was statistically significantly (inversely) associated with lithium levels, mainly in individuals with slightly impaired renal function (eGFR < 75 mL/min/1.73 m2). Besides, lithium levels were positively associated with age and alcohol intake. Using reduced rank regression, we identified a dietary pattern explaining 8.63% variation in plasma lithium levels. Higher lithium levels were associated with higher intakes of potatoes, leafy vegetables, root vegetables, fruits, tea, beer, wine and dietetic products and lower intakes of pasta, rice, pork, chocolate, sweets, soft drinks, other alcoholic beverages, sauces and snacks. Our observations suggest that plasma lithium levels are associated inversely with kidney function, particularly in individuals with slightly impaired renal function, and positively with age and alcohol intake. Lithium at physiological levels was moderately related to an exploratory dietary pattern.

Lithium Content of 160 Beverages and Its Impact on Lithium Status in Drosophila melanogaster.

Lithium (Li) is an important micronutrient in human nutrition, although its exact molecular function as a potential essential trace element has not yet been fully elucidated. It has been previously shown that several mineral waters are rich and highly bioavailable sources of Li for human consumption. Nevertheless, little is known about the extent in which other beverages contribute to the dietary Li supply. To this end, the Li content of 160 different beverages comprising wine and beer, soft and energy drinks and tea and coffee infusions was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, a feeding study in Drosophila melanogaster was conducted to test whether Li derived from selected beverages changes Li status in flies. In comparison to the average Li concentration in mineral waters (108 µg/L; reference value), the Li concentration in wine (11.6 ± 1.97 µg/L) and beer (8.5 ± 0.77 µg/L), soft and energy drinks (10.2 ± 2.95 µg/L), tea (2.8 ± 0.65 µg/L) and coffee (0.1 ± 0.02 µg/L) infusions was considerably lower. Only Li-rich mineral water (~1600 µg/L) significantly increased Li concentrations in male and female flies. Unlike mineral water, most wine and beer, soft and energy drink and tea and coffee samples were rather Li-poor food items and thus may only contribute to a moderate extent to the dietary Li supply. A novelty of this study is that it relates analytical Li concentrations in beverages to Li whole body retention in Drosophila melanogaster.

Lithium-Rich Mineral Water is a Highly Bioavailable Lithium Source for Human Consumption.

SCOPE: Lithium is an important trace element in human nutrition and medicine. Mineral and medicinal waters may represent a significant source of dietary lithium intake. METHODS AND RESULTS: The lithium concentration of 360 German mineral and 21 medicinal waters is determined. Based on a systematic screening, three different mineral waters exhibiting low (1.7 µg L-1 ), medium (171 µg L-1 ), and high lithium (1724 µg L-1 ) concentrations are chosen for an acute bioavailability study in male healthy volunteers. In Germany, a north-east to south-west gradient of analyzed lithium concentrations is observed in the 381 tested waters. The lithium concentration in the water is significantly correlated with its sodium (r = 0. 810), potassium (r = 0.716), and magnesium (r = 0.361), but not with its calcium concentration. In a randomized cross-over trial, volunteers (n = 3×10 each) drink 1.5 L of the respective mineral waters, and lithium concentrations in serum and urine are monitored over 24 h. Consumption of the mineral waters with a medium and high lithium content results in a dose-dependent response in serum lithium concentrations and total urinary lithium excretion. CONCLUSION: Lithium-rich mineral and medicinal waters may be an important and highly bioavailable lithium source for human consumption.

Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function.

Taurine is a nonproteinogenic ß-aminosulfonic acid. Important dietary sources of taurine are fish and seafood. Taurine interacts with ion channels, stabilizes membranes, and regulates the cell volume. These actions confirm its high concentrations in excitable tissues like retina, neurons, and muscles. Retinal degeneration, cardiomyopathy, as well as skeletal muscle malfunction are evident in taurine-deficient phenotypes. There is evidence that taurine counteracts lipid peroxidation and increases cellular antioxidant defense in response to inflammation. In activated neutrophils, taurine reacts with hypochloric acid to form taurine chloramine, which triggers the Kelch-like ECH-associated protein 1-nuclear factor E2-related factor 1 (Keap1-Nrf2) pathway. Consequently, Nrf2 target genes, such as heme oxygenase-1 and catalase, are induced. Furthermore, taurine may prevent an overload of reactive oxygen species (ROS) directly by an inhibition of ROS generation within the respiratory chain. Taurine affects mitochondrial bioenergetics and taurine-deficient mice exhibit an impaired exercise performance. Moreover, some studies demonstrate that taurine enhances the glycogen repletion in the postexercise recovery phase. In the case of taurine deficiency, many studies observed a phenotype known in muscle senescence and skeletal muscle disorders. Overall, taurine plays an important role in cellular redox homeostasis and skeletal muscle function.

Free Radical Scavenging and Cellular Antioxidant Properties of Astaxanthin.

Astaxanthin is a coloring agent which is used as a feed additive in aquaculture nutrition. Recently, potential health benefits of astaxanthin have been discussed which may be partly related to its free radical scavenging and antioxidant properties. Our electron spin resonance (ESR) and spin trapping data suggest that synthetic astaxanthin is a potent free radical scavenger in terms of diphenylpicryl-hydrazyl (DPPH) and galvinoxyl free radicals. Furthermore, astaxanthin dose-dependently quenched singlet oxygen as determined by photon counting. In addition to free radical scavenging and singlet oxygen quenching properties, astaxanthin induced the antioxidant enzyme paroxoanase-1, enhanced glutathione concentrations and prevented lipid peroxidation in cultured hepatocytes. Present results suggest that, beyond its coloring properties, synthetic astaxanthin exhibits free radical scavenging, singlet oxygen quenching, and antioxidant activities which could probably positively affect animal and human health.

Does mini-incision donor nephrectomy improve quality of life in living kidney donors?

BACKGROUND: Living kidney donation helps to avoid or reduce the time period of dialysis and on waiting lists in patients requiring a new organ. Mini-incision donor nephrectomy (MIDN) shows to result in better clinical outcome in comparison with traditional open donor nephrectomy (ODN). This study was performed to evaluate the impact of different surgical procedures on the quality of life (QoL) in patients that underwent donor nephrectomy. METHODS: The aim of the study was to detect differences in QoL assessed with the Short Form-36 Version 2 (SF-36v2) questionnaire between MIDN (n = 34) and ODN (n = 36). Furthermore, the development of QoL from prior to surgery until one yr afterwards, as well as outcomes of QoL in comparison with norm-based scores was investigated. RESULTS: Sixty-one of 70 patients, which is 87% (MIDN: 86%, ODN: 88%) resent a whole set questionnaires. QoL was similar at all time-points (prior to surgery, one wk, three months and one yr) in both groups. A tendency of better QoL in MIDN (Bodily Pain) after one wk was detectable (p = 0.075). Physical Component Summaries (PCS) significantly decreased from prior to surgery until one wk after surgery (p = 0.001) and improved significantly until three months (MIDN: p = 0.006, ODN: p = 0.001) and also until one yr after surgery (p = 0.002). Mental Component Summaries (MCS) were stable throughout the whole investigated time period. In comparison with norm-based scores, MIDN (p = 0.005) and ODN (p = 0.001) showed significantly higher PCS prior to, lower scores one wk after (p = 0.001), similar scores three months after and better scores (MIDN: p = 0.023, ODN: 0.015) one yr after surgery. Mental Component Scores were similar in both prior to and one wk after surgery. After three months and one yr scores were significantly better in MIDN (three months: p = 0.049, one yr: p = 0.037) and ODN (three months: 0.020, one yr: 0.073). CONCLUSION: Quality of life after living donor nephrectomy is not influenced by the surgical technique. Nevertheless the standardized instrument of the SF-36v2 Health Survey is a useful, practicable and universally interpretable tool to gain and estimate recovery from surgical procedures in the perioperative period and its development thereafter.

Mammalian target of rapamycin is activated in human gastric cancer and serves as a target for therapy in an experimental model.

The mammalian target of rapamycin (mTOR) has become an interesting target for cancer therapy through its influence on oncogenic signals, which involve phosphatidylinositol-3-kinase and hypoxia-inducible factor-1alpha (HIF-1alpha). Since mTOR is an upstream regulator of HIF-1alpha, a key mediator of gastric cancer growth and angiogenesis, we investigated mTOR activation in human gastric adenocarcinoma specimens and determined whether rapamycin could inhibit gastric cancer growth in mice. Expression of phospho-mTOR was assessed by immunohistochemical analyses of human tissues. For in vitro studies, human gastric cancer cell lines were used to determine S6K1, 4E-BP-1 and HIF-1alpha activation and cancer cell motility upon rapamycin treatment. Effects of rapamycin on tumor growth and angiogenesis in vivo were assessed in both a subcutaneous tumor model and in an experimental model with orthotopically grown tumors. Mice received either rapamycin (0.5 mg/kg/day or 1.5 mg/kg/day) or diluent per intra-peritoneal injections. In addition, antiangiogenic effects were monitored in vivo using a dorsal-skin-fold chamber model. Immunohistochemical analyses showed strong expression of phospho-mTOR in 60% of intestinal- and 64% of diffuse-type human gastric adenocarcinomas. In vitro, rapamycin-treatment effectively blocked S6K1, 4E-BP-1 and HIF-1alpha activation, and significantly impaired tumor cell migration. In vivo, rapamycin-treatment led to significant inhibition of subcutaneous tumor growth, decreased CD31-positive vessel area and reduced tumor cell proliferation. Similar significant results were obtained in an orthotopic model of gastric cancer. In the dorsal-skin-fold chamber model, rapamycin-treatment significantly inhibited tumor vascularization in vivo. In conclusion, mTOR is frequently activated in human gastric cancer and represents a promising new molecular target for therapy.