We like to move it - patients with schizophrenia spectrum disorders are impaired in estimating their physical fitness levels and benefit from individualized exercise.

BACKGROUND: People with schizophrenia spectrum disorders (SSD) engage less in physical activity than healthy individuals. The impact of subjectively assessed physical fitness levels on motivation for sports engagement and its relation to objective fitness parameters in SSD is unclear. METHODS: 25 patients with SSD (P-SSD) and 24 healthy controls (H-CON) participated in a randomized controlled study. Individual anaerobic thresholds (AT) were determined by an incremental exercise test and on separate days, aerobic exercise (cycling at 80% of workload at AT) and non-exercise control (sitting on an ergometer without cycling) sessions were performed. Demographic, clinical and objective physical fitness data (i.e., weekly physical activity, workload at AT, heart rate) were collected. Subjective physical fitness parameters were assessed before and after exercise and control sessions. RESULTS: Weekly physical activity in P-SSD was lower than in H-CON (p < 0.05) attributed to reduced engagement in sport activities (p < 0.001). Workload and percentage of predicted maximal heart rate at AT were also reduced in P-SSD compared to H-CON (both p < 0.05). Although objective and subjective physical fitness parameters were related in H-CON (p < 0.01), this relationship was absent in P-SSD. However, during exercise sessions subjective physical fitness ratings increased to a stronger extent in P-SSD than H-CON (p < 0.05). CONCLUSION: The missing relationship between subjective and objective physical fitness parameters in people with SSD may represent a barrier for stronger engagement in physical activity. Accordingly, supervised exercise interventions with individually adjusted workload intensity may support realistic subjective fitness estimations and enhance motivation for sports activity in individuals with SSD.

[Importance of sleep and circadian rhythm for energy metabolism]. / Bedeutung des zirkadianen Schlafrhythmus für den Energiestoffwechsel.

The circadian clock is a complex and highly specialized network of the human organism and is key for metabolic health. Circadian rhythms are modulated by behavioral patterns, physical activity, food intake as well as sleep loss and sleep disorders. Furthermore, an altered expression of clock genes (e. g. PERIOD1 and 2) can alter circadian rhythms. Chronodisruption, i. e. the alteration of circadian rhythms, is associated with a variety of mental and physical illnesses. Recent studies show a significant association between quantitative and qualitative sleep rhythm disturbances and an increasing prevalence of obesity. Furthermore, reduced sleep quality and duration lead to decreased glucose tolerance and insulin sensitivity, thus increasing the risk of developing type 2 diabetes. In addition to the core components of the metabolic syndrome, there are also changes in hormonal and neuronal signaling pathways impinging on human energy metabolism. This review provides an overview of the current literature highlighting the close link between circadian rhythms and human energy metabolism.

[Prevention and treatment of cachexia : Exercise and nutritional therapy]. / Prävention und Behandlung der Kachexie : Bewegungs- und Ernährungstherapie.

BACKGROUND: Cachexia is a multifactorial and complex syndrome characterized by progressive functional impairment and ongoing loss in quality of life, which lead to a deterioration of the prognosis for affected patients. The prevalence of cachexia can be very high and is up to 80 % in patients with malignant tumors. OBJECTIVE: The aim of the study was to assess the relevance of exercise and nutrition in the prevention and therapy of cachexia. METHODS: An evaluation of the current literature on exercise and nutritional therapy in patients with cachexia or with advanced stage diseases where a high prevalence of cachexia is probable, was carried out. RESULTS: There is a lack of scientific evidence for the benefits of exercise in cachexia. A major problem of relevant studies was that cachexia was frequently not defined according to valid criteria; however, data indicate a benefit of exercise training in patients with advanced diseases associated with a high prevalence of cachexia. A solely nutritional intervention and dietary counselling seem to be of minimal benefit. The administration of omega 3 fatty acids is controversially discussed. CONCLUSION: Although there is a lack of data on the effects of exercise and nutritional therapy in cachexia, there is evidence for the benefits. The present data indicate the necessity for the use of a multimodal treatment including exercise, nutritional and pharmacological therapy in cachexia. There is a great necessity for prospective studies.

Correction factors for the calculation of metabolic equivalents (MET) in overweight to extremely obese subjects.

BACKGROUND/OBJECTIVES: The metabolic equivalent (MET) is a construct that is commonly used to quantify physical activity as well as exercise performance. 'One MET' is equal to a resting oxygen uptake of 3.5 ml O2 kg(-1) min(-)(1). However, this assumption is unlikely valid in obese subjects. The aim of our study was to quantify the difference between calculated and measured METs in overweight to severely obese subjects and to provide body mass index (BMI)-specific MET correction factors. SUBJECTS/METHODS: Resting oxygen uptake (VO2-REE) was measured in 1331 patients with a BMI >25 kg m(-2) (72.0% women; age: 42.5 ± 13.0 years; BMI: 42.5 ± 7.0 kg m(-)(2)) by indirect calorimetry and MET-REE, that is, VO2-REE related to body weight was calculated. Six hundred and fifty-two subjects (70.9% women) additionally underwent a bicycle cardiopulmonary exercise test for measurement of maximal MET (MET peak). RESULTS: Mean MET-REE was 2.47 ± 0.33 ml O2 kg(-1) min(-1) in women and 2.62 ± 0.34 ml O2 kg(-1) min(-1) in men, that is, markedly lower than the expected 3.5 ml O2 kg(-1) min(-1). MET-REE decreased with increasing BMI (P<0.001 for both sexes). On this dataset, gender-specific MET correction factors were developed for distinct BMI groups. During the exercise test, women performed 4.4 ± 1.3 MET peak and men 4.7 ± 1.3. After applying our correction factors, MET peak increased to 6.2 ± 1.7 and 6.1 ± 1.6, respectively. CONCLUSIONS: Data indicate that the commonly used 1-MET value of 3.5 ml O2 kg(-)(1) min(-)(1) largely overestimates values in overweight to severely obese subjects. Our correction factors can help to reduce this systematic error and thus appear to be valuable for clinical practice as well as research studies.

Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery.

OBJECTIVE: Neuroimaging studies have demonstrated alterations in brain activity in obese (OB) subjects that might be causally linked to their disorder. Roux-en Y gastric bypass (RYGB) surgery induces a marked and sustained weight loss and may affect brain activity. The aim of this study was to compare brain activity pattern between severely OB women (n=11), normal-weight women (NW, n=11) and previously severely OB women who had undergone RYGB surgery (RYGB, n=9) on average 3.4±0.8 years (all >1 year) before the experiment. DESIGN: Brain activity was assessed by functional magnetic resonance imaging during a one-back task containing food- and non-food-related pictures and during resting state. Hunger and satiety were repeatedly rated on a visual analog scale during the experiment. RESULTS: As compared with NW and also with RYGB women, OB women showed (1) a higher cerebellar and a lower fusiform gyrus activity during the visual stimulation independently of the picture category, (2) a higher hypothalamic activation during the presentation of low- vs high-caloric food pictures, (3) a higher hippocampal and cerebellar activity during the working memory task and (4) a stronger functional connectivity in frontal regions of the default mode network during resting state. There were no differences in brain activity between the NW and RYGB women, both during picture presentation and during resting state. RYGB women generally rated lower on hunger and higher on satiety, whereas there were no differences in these ratings between the OB and NW women. CONCLUSION: Data provide evidence for an altered brain activity pattern in severely OB women and suggest that RYGB surgery and/or the surgically induced weight loss reverses the obesity-associated alterations.

Whole body vibration added to endurance training in obese women - a pilot study.

Whole body vibration (WBV) training is an increasingly popular training method that is strongly promoted for weight loss, but scientific data on its effectiveness, particularly in obese subjects, are sparse. 14 obese women (BMI: 37.4 ± 1.3 kg/m2) randomized to 2 different groups (each n=7) participated in a 6-week endurance training program that was either combined or not combined with additional WBV training. Anthropometric measures, phase angle and body composition (assessed by bioelectrical impedance analysis; BIA), and resting energy expenditure (REE) were obtained before and after the training program. Body weight did not change during the training period (P=0.87), but waist circumference decreased in both groups (P=0.007; WBV: -3.4 ± 1.4 cm; no-WBV: -1.7 ± 0.7 cm) independent of WBV training (P=0.29 for group×time interaction). BIA revealed an enhancing effect of WBV training in comparison to no-WBV training on the phase angle (+0.20 ± 0.12° vs. -0.19 ± 0.12°; P=0.04) and calculated body cell mass (+0.8 ± 0.2 vs. -0.3 ± 0.4 kg; P=0.02), while calculated percentage fat mass decreased in both conditions (P=0.05) to similar extent (P=0.59; WBV: -0.8 ± 0.2%; no-WBV: -0.4 ± 0.5%). REE increased across the training (P=0.01; WBV: +77 ± 33 kcal/24 h; no-WBV: +68 ± 34 kcal/24 h), with this increase again not depending on WBV condition (P=0.85). Results of our pilot study in obese women provide preliminary evidence for a beneficial effect of WBV, when added to endurance training, on the bioelectrical phase angle, an increasingly recognized marker of individual's health status.

Plasma omentin-1 levels are related to exercise performance in obese women and increase upon aerobic endurance training.

INTRODUCTION: Omentin-1 is an adipokine that is primarily released from visceral adipose tissue stromal cells. The effects of exercise on omentin-1 regulation are not clear so far. Therefore, the effect of endurance training on circulating omentin-1 levels and its relation to exercise performance was assessed in obese women. METHODS: 13 obese women (age: 44.8±3.3 years; BMI: 37.8±1.3 kg·m(-2)) participated in a 6-week endurance training program. Omentin-1, metabolic traits (glucose, insulin, HOMA-IR, lipids profile), and exercise performance (cardiopulmonary exercise test (V̇O2,peak, Wpeak), 6 min walking test, 6MWT) were assessed before and after the training. RESULTS: After the training program circulating omentin-1 were 10.4% higher than before the program (690±50 ng·ml(-1) vs. 618±42; p=0.04), while body weight remained unchanged (p=0.9). Before training, omentin-1 levels were significantly correlated with Wpeak (given in absolute and relative values) as well as with 6MWT (all r≥0.603; all p≤0.029) and the correlations with absolute as well as relativeV̇O2,peak approached significance (both r≥0.534; both p≤0.060). After training, respective correlations were generally weaker and did not reach significance any longer (all r≤0.465; all p≥0.109). Neither before nor after the training program were significant correlations found between omentin-1 levels and the other measured metabolic blood markers (all p≥0.157). DISCUSSION: Data show a rather strong relationship between exercise performance and circulating omentin-1 levels as well as an increase of the adipokine in response to 6-week of endurance training in obese women. Our findings may hint to a skeletal muscle-adipose tissue crosstalk in regard of omentin-1 regulation.

Development of an Escherichia coli whole cell biocatalyst for the production of L-amino acids.

A whole cell biocatalyst for the enzymatic production of L-amino acids from hydantoins was created by coexpressing the genes encoding the L-hydantoinase, the L-N-carbamoylase and the hydantoin racemase from Arthrobacter aurescens in Escherichia coli. In order to construct a well balanced reaction system the enzymatic activity in the cells was varied by using vectors with different copy numbers for expression of the genes. Derivatives of pSC101, pACYC184 and pBR322 were employed for the various constructions and in one construct the hydantoinase gene was integrated into the E. coli chromosome. All constructs carried the E. coli rhamnose promoter system enabling gene expression control by transcriptional regulation. The productivity for L-tryptophan from the corresponding hydantoin was more than 6-fold higher than achieved with Arthrobacter aurescens.

Cloning, nucleotide sequence and expression of a new L-N-carbamoylase gene from Arthrobacter aurescens DSM 3747 in E. coli.

An L-N-carbamoyl amino acid amidohydrolase (L-N-carbamoylase) from Arthrobacter aurescens DSM 3747 was cloned in E. coli and the nucleotide sequence was determined. After expression of the gene in E. coli the enzyme was purified to homogeneity and characterized. The enzyme was shown to be strictly L-specific and exhibited the highest activity in the hydrolysis of beta-aryl substituted N alpha-carbamoyl-alanines as e.g. N-carbamoyl-tryptophan. Carbamoyl derivatives of beta-alanine and charged aliphatic amino acids were not accepted as substrates. The N-carbamoylase of A. aurescens DSM 3747 differs from all known enzymes with respect to its substrate specificity although amino acid sequence identity scores of 35-38% to other N-carbamoylases have been detected. The enzyme consists of two subunits of 44,000 Da, and has an isoelectric point of 4.3. The optima of temperature and pH were determined to be 50 degrees C and pH 8.5 respectively. At 37 degrees C the enzyme was completely stable for several days.

[Pneumocystis carinii pneumonia in HIV-positive and HIV-negative patients]. / Pneumocystis-carinii-Pneumonien bei HIV-positiven und -negativen Patienten.

Bronchoalveolar lavage was used in 170 immunocompromised patients for detection of causative agents. Pneumocystis carinii was isolated 18 times from HIV-positive patients and 14 times from patients suffering from immunodeficiencies due to various other diseases. Patients with AIDS were in better clinical condition, had fewer infiltrates on chest x-ray, a higher oxygen partial pressure and lower LDH-plasma concentration than HIV-negative patients. In spite of the earlier stage of the disease patients with AIDS experience prodromal symptoms for a longer time and the number of isolated pneumocystis was larger. Mortality in AIDS patients was significantly lower than in patients with other causes of immunodeficiency.

Cardio-respiratory fitness is independently associated with cardio-metabolic risk markers in severely obese women.

INTRODUCTION: Many studies have shown an inverse relationship between cardio-respiratory fitness and cardio-metabolic risk markers in normal-weight to moderately obese subjects. However, whether such a relationship exists in severely obese subjects is not known. MATERIALS AND METHODS: Cardio-respiratory fitness was measured by bicycle spiroergometry in 308 severely obese women (all BMI>35 kg/m(2)). The following cardio-metabolic risk markers were assessed: Glycolized hemoglobin levels (HbA1c), fasting glucose, insulin, calculated HOMA index, triglycerides (TG), total, low-, high-density cholesterol (Chol, LDL; HDL), Chol/HDL-Ratio, and uric acid. Computed multiple stepwise linear regression models generally included age, weight and height as independent variables. RESULTS: Multiple stepwise linear regression models indicated that peak but not aerobic threshold related cardio-respiratory fitness indices were independently of age, weight and height associated with several cardio-metabolic risk markers. Specifically, maximally achieved load (Watt-peak) explained 1.4% of the variance in glucose levels (beta= -0.13; p=0.04) and 2.8% of the variance in HbA1c levels (beta= -0.18; p=0.01), while maximally achieved O2-uptake explained 3.9% of the variance in TG levels (beta= -0.20, p=0.001). CONCLUSION: Our data for the first time indicate that cardio-respiratory fitness is independently associated with cardio-metabolic risk markers in severely obese women.

The hedonic drive to consume palatable foods appears to be lower in gastric band carriers than in severely obese patients who have not undergone a bariatric surgery.

BACKGROUND: We have recently shown that severely obese patients display a markedly enhanced drive to consume palatable food, and that this hedonic hunger is reduced after gastric bypass surgery. Adjustable gastric banding is another frequently performed bariatric operation with unknown effects on hedonic hunger motivation. Here, we compared the level of hedonic hunger in patients who have undergone a gastric banding with that in severely obese patients who have not undergone a bariatric operation and nonobese controls. METHODS: In a cross-sectional case-control study, 116 gastric banding patients, 138 severely obese patients, and 133 nonobese controls were examined with the Power of Food Scale (PFS), a questionnaire that reliably measures an individual's motivation to consume highly palatable food. RESULTS: While the severely obese patients displayed markedly higher aggregated PFS scores and scores on the subdomain "generally available" and "physically present" food than the nonobese controls (all P < 0.001), the gastric banding patients showed significantly lower scores on all of these variables than the obese patients (all P < 0.001). However, the generally available food score was still higher in gastric banding patients than in the nonobese controls (P = 0.001). CONCLUSIONS: Data suggest that adjustable gastric banding may reduce the excessive appetite for palatable foods in severely obese patients. This suggestion needs to be confirmed in longitudinal studies.

[Procaine infusion for pain treatment of acute pancreatitis: a randomized, placebo-controlled double-blind trial]. / Procaininfusion zur Schmerzbehandlung bei akuter Pankreatitis: Eine randomisierte, placebokontrollierte Doppelblind-Studie.

BACKGROUND AND OBJECTIVE: Acute pancreatitis is commonly associated with severe abdominal pain, making early pain relief a primary goal of the treatment. This study was undertaken to assess the efficacy of a continuous intravenous (i.v.) infusion of procaine compared with that of a placebo infusion in providing pain relief in patients with acute pancreatitis. PATIENTS AND METHODS: 42 patients with acute pancreatitis were prospectively randomized to receive, in a double-blind setting, a continuous i.v. infusion of a 1% solution of procaine (procaine group) or placebo (placebo group, receiving a 0.9% saline solution) on the first three days of treatment in a hospital setting. The maximal infusion rate of the procaine solution was 8 ml/h, i.e. 1.92 g/24 h. The rate and total amount of infused fluid was similar in the placebo group. Additionally buprenorphine (Temgesic, sublingual [s.l.]) were given on demand for additional pain relief. RESULTS: The gender ratio and the severity of the pancreatitis (APACHE II score, Ranson score) were comparable between the two groups, while the patients of the control group were eight years older (50.1 2.3 vs. 58.4 3.1; p = 0.039). The i.v. infusion of procaine did not reduce the demand for buprenorphine in the procaine group and was similar to that in the placebo group (p=0.88). Furthermore, explorative data analysis revealed that patients of the procaine group had higher bodily discomfort and nausea scores and also tended to feel more pain than the patients of the placebo group. DISCUSSION: These data do not indicate a clinically meaningful analgesic effect of i.v. infusion of procaine (maximal amount. 1.92 g/24h) in patients with acute pancreatitis, but suggested that this infusion actually increased the feeling of bodily discomfort and nausea. We thus conclude that a constant i.v. infusion of procaine should no longer be recommended for pain relief in patients with acute pancreatitis anymore.

Purification of recombinant hydantoinase and L-N-carbamoylase from Arthrobacter aurescens expressed in Escherichia coli: comparison of wild-type and genetically modified proteins.

Two enzymes, hydantoinase (HyuH) and L-N-carbamoylase (HyuC), are required for the biocatalytic production of natural and unnatural, optically pure L-amino acids starting from D,L-5-monosubstituted hydantoins using the so called 'hydantoinase-method'. For the preparation of immobilized enzymes, which omit several drawbacks of whole cell biocatalysts, purified or at least enriched HyuH and HyuC have to be provided. In order to simplify existing purification protocols several genetically modified derivatives of HyuH and HyuC from Arthrobacter aurescens DSM 3747 have been cloned and expressed in E. coli. A fusion protein consisting of maltose-binding protein (MalE) and HyuH resulted in an enhanced solubility of the hydantoinase, which easily forms inclusion bodies. On the other hand the fusion protein could easily be purified with high yield (76%) by just one chromatographic step (amylose resin) and the complex purification protocol of the wild-type enzyme could therefore be simplified and shortened significantly. Interestingly, the specific activity of the MalE-HyuH fusion protein was as high as the wild-type enzyme despite that the molecular mass was doubled. A second modification of HyuH carrying a histidine-tag was efficiently bound to a metal affinity matrix but inactivated completely during elution from the column at either low pH or in the presence of imidazole. In the case of HyuC, an aspartate-tag has been added to the biocatalyst to allow an integrated purification-immobilization procedure since this enzyme is immobilized efficiently only via its carboxylic groups. The diminished isoelectric point of the Asp-tagged HyuC resulted in a simplified purification procedure. Compared to the wild-type enzyme expressed in E. coli HyuC-Asp6 was shifted off the elution range of the contaminating proteins and higher purification factors were obtained even in the capturing step. In contrast to HyuH, it was possible to purify a L-N-carbamoylase carrying a histidine-tag to apparent homogeneity using immobilized metal affinity chromatography. Therefore, the existing three step purification protocol was reduced to one chromatographic step and the yield of this relatively unstable protein enhanced remarkably.

High-cell-density fermentation for production of L-N-carbamoylase using an expression system based on the Escherichia coli rhaBAD promoter.

A high-cell-density fed-batch fermentation for the production of heterologous proteins in Escherichia coli was developed using the positively regulated Escherichia coli rhaBAD promoter. The expression system was improved by reducing of the amount of expensive L-rhamnose necessary for induction of the rhamnose promoter and by increasing the vector stability. Consumption of the inducer L-rhamnose was inhibited by inactivation of L-rhamnulose kinase encoding gene rhaB of Escherichia coli W3110, responsible for the first irreversible step in rhamnose catabolism. Plasmid instability caused by multimerization of the expression vector in the recombination-proficient W3110 was prevented by insertion of the multimer resolution site cer from the ColE1 plasmid into the vector. Fermentation experiments with the optimized system resulted in the production of 100 g x L(-1) cell dry weight and 3.8 g x L(-1) of recombinant L-N-carbamoylase, an enzyme, which is needed for the production of enantiomeric pure amino acids in a two-step reaction from hydantoins.

Cloning, nucleotide sequence and expression of a hydantoinase and carbamoylase gene from Arthrobacter aurescens DSM 3745 in Escherichia coli and comparison with the corresponding genes from Arthrobacter aurescens DSM 3747.

The genes encoding hydantoinases (hyuH1) and carbamoylases (hyuC1) from Arthrobacter aurescens DSM 3745 and Arthrobacter aurescens DSM 3747 (hyuH2, hyuC2) were cloned in Escherichia coli and the nucleotide sequences determined. The hydantoinase genes comprised 1,377 base pairs and the carbamoylase genes 1,239 base pairs each. Both hydantoinases, as well as both carbamoylases, showed a high degree of nucleotide and amino acid sequence identity (96-98%). The hyuH and hyuC genes were expressed in E. coli under the control of the rhamnose promoter and the different specific activities obtained in E. coli crude extracts were compared to those produced by the original hosts. For purification the hyuH2 gene was expressed as a maltose-binding protein (MalE) and as an intein-chitin binding domain (CBD) fusion in E. coli. The expression of malE-hyuH2 resulted in the production of more soluble and active protein. With respect to temperature stability, optimal pH and optimal temperature, substrate and stereospecificity, the purified fusion enzyme exhibited properties similar to those of the wild-type enzyme.

[Pneumonia in immunocompromised patients: the value of non-biopsy bronchoscopic examination procedures in the diagnosis of pathogens]. / Pneumonien bei abwehrgeschwächten Patienten: Stellenwert nicht bioptischer bronchoskopischer Untersuchungsverfahren in der Erregerdiagnostik.

Bronchoscopy was performed on 101 immunocompromised patients with fever and pulmonary infiltrates. Underlying diseases were mainly hematological malignancies. In 71% of cases, etiology of pneumonia was clarified by nonbioptic bronchoscopic methods (bronchoalveolar lavage, bronchial secretions, protected specimen brush). In 51% of cases, empirical antibiotic treatment was modified following bronchoscopy. In patients with early bronchoscopy a better prognosis regarding healing and survival was observed than in those cases, where bronchoscopy was performed later during pneumonia. Bronchoalveolar lavage was particularly suited for diagnosis of Pneumocystis carinii and pneumonia due to viruses or Legionella. Sensitivity and specificity of bronchoscopy were lower for diagnosis of mycotic pneumonia and of Gram-negative or Gram-positive bacteria.