Assessing detailed metabolism in exercising persons minute-to-minute has not been possible. We developed a "drop-of-blood" platform to fulfill that need. Our study aimed not only to demonstrate the ...utility of our methodology, but also to give insights into unknown mechanisms and new directions.
We developed a platform, based on gas chromatography and mass spectrometry, to assess metabolism from a blood-drop. We first observed a single volunteer who ran 13 km in 60 min. We particularly monitored relative perceived exertion (RPE). We observed that 2,3-bisphosphoglycerate peaked at RPE in this subject. We next expanded these findings to women and men volunteers who performed an RPE-based exercise protocol to RPE at
O
20.9% or
O
14.5% in random order.
At 6 km, our subject reached his maximum relative perceived exertion (RPE); however, he continued running, felt better, and finished his run. Lactate levels had stably increased by 2 km, ketoacids increased gradually until the run's end, while the hypoxia marker, 2,3 bisphosphoglycerate, peaked at maximum relative perceived exertion. In our normal volunteers, the changes in lactate, pyruvate,
hydroxybutyrate and
hydroxybutyrate were not identical, but similar to our model proband runner.
Glucose availability was not the limiting factor, as glucose availability increased towards exercise end in highly exerted subjects. Instead, the tricarboxylic acid→oxphos pathway, lactate clearance, and thus and the oxidative capacity appeared to be the defining elements in confronting maximal exertion. These ideas must be tested further in more definitive studies. Our preliminary work suggests that our single-drop methodology could be of great utility in studying exercise physiology.
Autosomal-dominant hypertension with brachydactyly is a salt-independent Mendelian syndrome caused by activating mutations in the gene encoding phosphodiesterase 3A. These mutations increase the ...protein kinase A-mediated phosphorylation of phosphodiesterase 3A resulting in enhanced cAMP-hydrolytic affinity and accelerated cell proliferation. The phosphorylated vasodilator-stimulated phosphoprotein is diminished, and parathyroid hormone-related peptide is dysregulated, potentially accounting for all phenotypic features. Untreated patients die prematurely of stroke; however, hypertension-induced target-organ damage is otherwise hardly apparent. We conducted clinical studies of vascular function, cardiac functional imaging, platelet function in affected and nonaffected persons, and cell-based assays. Large-vessel and cardiac functions indeed seem to be preserved. The platelet studies showed normal platelet function. Cell-based studies demonstrated that available phosphodiesterase 3A inhibitors suppress the mutant isoforms. However, increasing cGMP to indirectly inhibit the enzyme seemed to have particular use. Our results shed more light on phosphodiesterase 3A activation and could be relevant to the treatment of severe hypertension in the general population.
Objectives: Drinking green tea is associated with many health benefits, including increased fat oxidation. We tested the hypothesis that epigallocatechin-3-gallate (EGCG), the main green tea ...catechin, increases fat oxidation in obese men. Methods: Ten healthy overweight/obese males (body mass index 31.3±0.8 kg/m2) were studied in a randomized, placebo-controlled, double-blind crossover trial. Study supplements were low EGCG (300 mg), high EGCG (600 mg), caffeine (200 mg), EGCG/caffeine (300 mg/200 mg) or placebo and were taken orally for 3 days. At the third day of supplementation, O2 consumption and CO2 production was measured by indirect calorimetry to assess energy expenditure and fat oxidation over 4 h each after overnight fasting and after a standardized test meal. Results: Energy expenditure was not affected by any supplementation, neither after overnight fasting nor after the test meal. During the first 2 h after overnight fasting, fat oxidation increased by 7.7 (not significant, NS), 15.2 (NS), 26.3 (P<0.05 vs placebo) and 35.4% (P<0.01 vs placebo and low EGCG), for low EGCG, high EGCG, caffeine and EGCG/caffeine, respectively. During the first 2 h after the meal, the mean increase in fat oxidation was 33.3 (P<0.05 vs placebo), 20.2 (NS), 34.5 (P<0.05 vs placebo) and 49.4% (P<0.05 vs placebo) for low EGCG, high EGCG, caffeine and EGCG/caffeine, respectively. Conclusions: Low EGCG increases postprandial fat oxidation in obese men and this to the same extent as 200 mg caffeine, whereas high EGCG does not exert this effect. Fasting fat oxidation is increased only by caffeine (with or without EGCG). There is no synergism of low EGCG and 200 mg caffeine. Energy expenditure is not affected by EGCG.
The evidence that physical exercise lowers metabolic and cardiovascular risk is undisputed. Normobaric hypoxia training has been introduced to facilitate the effects of exercise. We tested the ...hypothesis that hypoxia training augments exercise‐related effects. We randomized 23 men with metabolic‐syndrome to single‐blinded exercise at normoxia (FiO2 21%) or hypoxia (FiO2 15%). Six weeks endurance training on a treadmill, 3 days per week, over 60 min at 60% VO2max was required. The study included the following: (1) metabolic phenotyping by indirect calorimetry and adipose and muscle tissue microdialysis to gain insight into effects on resting, postprandial, and exercise metabolism, (2) cardiac imaging, and (3) biopsies. Primary endpoint was the change in cardiorespiratory fitness; secondary endpoints were as follows: changes in body weight, waist circumference, blood pressure, cardiac dimensions, and adipose and muscle tissue metabolism and gene expression. Our subjects reduced waist circumference and improved several cardiovascular risk markers including blood pressure. However, these effects were similar in both training groups. Cardiac dimensions were not influenced. We focused on glucose metabolism. After an oral glucose load, adipose tissue metabolism was significantly shifted to a more lipolytic state under hypoxia, whereas muscle metabolism was similar under both conditions. Postprandial energy expenditure was significantly increased under hypoxia, whereas activity energy expenditure was improved under normoxia. Gene expression was not consistently influenced by FiO2. Adipose tissue triglyceride lipase, leptin, and hypoxia‐inducible factor‐alpha expression were increased by normoxia but not hypoxia.
We had reported earlier that altitude (normobaric hypoxia) training at FIO2 15% might facilitate the effects of exercise training in normal people. We now tested this hypothesis in men with the metabolic syndrome. Exercise lowered blood pressure, reduced waist circumference, and improved metabolism. Adding hypoxia during training, however, caused no further improvement.
Context: Type 2 familial partial lipodystrophy (FPLD) is an autosomal-dominant lamin A/C-related disease associated with exercise intolerance, muscular pain, and insulin resistance. The symptoms may ...all be explained by defective metabolism; however, metabolism at the tissue level has not been investigated.
Objective: We hypothesized that in FPLD, insulin resistance and impaired aerobic exercise capacity are explained by a common underlying mechanism, presumably a muscular metabolic defect.
Patients and Methods: Carbohydrate and lipid metabolism was studied on 10 FPLD patients, one patient with limb-girdle muscular dystrophy (LGMD1B, a different lamin A/C disease), and 10 healthy control subjects before and during an oral glucose tolerance test by indirect calorimetry and im microdialysis. Muscle biopsies were taken for in vitro studies.
Results: We observed marked increased skeletal muscle fatty acid β-oxidation rate in vitro and in vivo, even after glucose ingestion in FPLD patients. However, fatty acid oxidation was largely incomplete and accompanied by increased ketogenesis. The lipid oxidation abnormality was associated with impaired glucose disposition through reduction in glucose oxidation, rather than decreased cellular glucose uptake. A microarray showed down-regulation of complex I respiratory chain, glycolysis, and nuclear transport genes. Although not overtly insulin resistant, the LGMD1B patient showed similar metabolic derangements as the FPLD patients.
Conclusions: Our study suggests imbalance between lipid oxidation and oxidative glucose metabolism in FPLD and LGMD1B patients. The observation suggests an intrinsic defect in skeletal muscle metabolism due to lamin A/C dysfunction. The metabolic FPLD phenotype likely results from this intrinsic defect combined with lipodystrophic “lipid pressure” due to decreased adipose tissue lipid storage capacity.
LMNA mutations are associated with an imbalance between lipid oxidation and oxidative glucose metabolism likely caused by intrinsic defects in skeletal muscle metabolism.
Abstract Background It is known that most adult patients with epilepsy often have poor knowledge of their disorder, treatment options, and social and vocational consequences, despite the huge amount ...of information available. Being pressed for time, health care professionals often are not able to provide the repetitive counseling and instruction necessary to address epilepsy care adequately. Therefore educational programs are considered extremely important in filling the gap. Method For German-speaking countries, two educational programs called famoses, modulares Schulungsprogramm Epilepsie f ű r Familien modular service package epilep s y for families, were developed by a multidisciplinary group of neuropediatricians, psychologists, social workers, and educators. The aims of the famoses programs are to improve children’s and parents’ knowledge about epilepsy and to help patients of childhood age and their parents achieve a better understanding of their disease, gain more self-confidence, and reduce specific fears regarding epilepsy. famoses comprises two different educational programs: famoses for kids with epilepsy within the developmental period of ages 7 to 13, and famoses for parents or caretakers. The programs are designed for interactive small-group education. Results The child-centered educational program is based on a fictional story: The children are sailors on a virtual cruise, sailing from island to island, accompanied by educated trainers. On each island there is something new to discover about epilepsy. The parent (and caretaker)-centered educational program covers different topics—overview and content of the program, basic knowledge, diagnostics, therapy, prognosis and development, and living with epilepsy—within six modules. The program was implemented in Germany and Switzerland in the spring of 2005 and is now operating in different epilepsy centers. Conclusion Within comprehensive therapeutic management of epilepsy, educational programs for patients, and for parents (caretakers) of children with epilepsy, are considered to be extremely important. Such educational programs have two main goals: to increase knowledge about the disorder, and to strengthen the patients’ responsibility for themselves, with the consequence of living with as few limitations as possible. famoses is an effective component of this comprehensive care. The program has been operating successfully in different epilepsy centers in Germany and Switzerland since the spring of 2005.
...there are some slips and lapses in execution because of a too high workload. A positive impact of systematic reviews in wound care is that they have stimulated research funders to commission high ...quality research to fill the gaps, particularly in the UK where the National Institute for Health Research is one of the world’s largest independent funders of wounds research 2-4. ...wounds research has failed to develop a basic theoretical understanding. Lessons learned from a pilot study on a novel inter-professional training course Katrin Balzer1, Rhian Schröder1, Anne Junghans2, Ute Stahl3, Jens-Martin Träder4, Sascha Köpke1 1Nursing Research Unit, Institute for Social Medicine and Epidemiology, University of Lübeck, Lübeck, Schleswig-Holstein, 23538, Germany; 2Department of Nursing and Management, University of Applied Sciences Hamburg, Hamburg, 20099, Germany; 3AMEOS Krankenhausgesellschaft, Neustadt, Schleswig-Holstein, 23730, Germany; 4Institute for Family Medicine, University of Lübeck, Lübeck, Schleswig-Holstein, 23538, Germany Correspondence: Katrin Balzer (katrin.balzer@uksh.de) Background Insufficient knowledge among nurses and medical doctors regarding evidence-based care recommendations and nurse-doctor-communication failures are assumed to be important determinants of malpractices in dementia care.
The effects of shifted working and sleeping phases on the diurnal blood pressure rhythm were investigated in 15 physically working industrial shift workers at a slowly rotated three-shift system. ...Ambulatory 24-h blood pressure monitoring was performed during the morning and night shifts. In the two shifts the mean 24-h blood pressure was identical. There were no differences in the blood pressure levels in the sleeping phases or in the working periods between the two 24-h cycles. Diurnal blood pressure fluctuations had equal amplitudes. Corresponding to the lag between the working period there was a phase difference of 8 h between the 24-h blood pressure curves. At this lag, there was a high correlation between the mean hourly blood pressure values (r = 0.683). Twenty-four-hour blood pressure curves during the first and last day of a night shift were nearly equal. Thus the effects of shift rotation on the 24-h blood pressure profile were fully expressed within the first 24 hours. The immediate and complete adaptation of the 24-h blood pressure curve to shifted activity and sleeping phases indicates that activity determines the diurnal blood pressure profile. The blood pressure is largely independent of internal circadian rhythm.
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