[Guideline for Long-Term Oxygen Therapy - S2k-Guideline Published by the German Respiratory Society]. / Leitlinie zur Langzeit-Sauerstofftherapie.

Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.

Serum carotenoid and tocopherol concentrations and risk of asthma in childhood: a nested case-control study.

BACKGROUND: The antioxidant hypothesis regarding the risk of asthma in childhood has resulted in inconsistent findings. Some data indicate that the role of antioxidants in childhood asthma risk may have a critical time window of effect, but only a well-designed longitudinal cohort study can clarify this hypothesis. OBJECTIVE: To study the longitudinal associations between serum carotenoid and tocopherol concentrations during the first 4 years of life and asthma risk by the age of 5 years. METHODS: Based on a case-control design nested within a Finnish birth cohort, 146 asthma cases were matched to 270 controls on birth time, sex, genetic risk, and birth place. Non-fasting blood samples were collected at the ages of 1, 1.5, 2, 3, and 4 years and serum carotenoids and tocopherols were analysed. Parents reported the presence and age at start of persistent doctor-diagnosed asthma in the child at the age of 5 years. Data analyses were conducted using generalized estimating equations. RESULTS: We did not find strong associations between serum carotenoids and tocopherols and the risk of asthma based on age-specific and longitudinal analyses. Both lower and higher quarters of α-carotene and γ-tocopherol increased the risk of asthma. CONCLUSIONS: The current findings do not support the suggestion that the increased prevalence of asthma may be a consequence of decreased intake of antioxidant nutrients. Moreover, we did not confirm any critical time window of impact of antioxidants on asthma risk. Replication of these findings in similar longitudinal settings will strengthen this evidence base.

Myosin and SERCA isoform expression in denervated slow-twitch muscle of euthyroid and hyperthyroid rabbits.

Changes in the isoform patterns of myosin heavy chains (MHC) and Ca2+-ATPase (SERCA) were studied in long-term (72 days) denervated slow-twitch soleus muscles of euthyroid and hyperthyroid rabbits. MHC isoforms were separated electrophoretically. SERCA isoforms were assessed by electrophoretic separation of the trypsin-digested and phosphorylated fragments. Denervation led to pronounced slow-to-fast transitions with increases in the fast MHC and fast SERCA1a isoforms. Hyperthyroidism had no significant effect on the denervation-induced changes in SERCA isoforms, but led to slight increases in the relative concentrations of the fast MHC isoforms. A high correlation existed between the relative concentrations of slow myosin and SERCA2a in both innervated euthyroid and hyperthyroid soleus muscles. This correlation, however, seems to be less tight in denervated soleus muscles.

Coordinated fast-to-slow transitions of myosin and SERCA isoforms in chronically stimulated muscles of euthyroid and hyperthyroid rabbits.

Changes in the patterns of myosin heavy chain (MHC) isoforms, isomyosins, and Ca(2+)-ATPase (SERCA) isoforms were studied in long-term (72 d) stimulated fast-twitch extensor digitorum longus (EDL) and tibialis anterior (TA) muscles of euthyroid and hyperthyroid rabbits. The chronic low-frequency stimulation-induced fast-to-slow transitions in MHC isoforms, isomyosins and SERCA isoforms were pronounced in muscles from euthyroid rabbits, but less pronounced in muscles from hyperthyroid rabbits. Thus, hyperthyroidism counteracted to same extent the stimulation-induced fast-to-slow transition. Analyses of all parameters were performed on the same individual muscles, providing information on the co-ordinated expression of SERCA and myosin isoforms. A high correlation (r = 0.97) was detected between relative concentrations of slow SERCA2a and slow MHCI isoforms. This correlation persisted under all experimental conditions, suggesting a co-ordinated expression of slow myosin and Ca(2+)-ATPase isoforms. Conversely, fast SERCA1a was correlated to fast myosin isoforms as a whole.

Expression of an alpha-cardiac like myosin heavy chain in diaphragm, chronically stimulated, and denervated fast-twitch muscles of rabbit.

An additional slow fibre type, type I alpha, is detected in diaphragm and appears in fast-twitch hindlimb muscles of rabbit under the influence of altered neuromuscular activity. Type I alpha fibres were delineated from fibres expressing myosin heavy chain I beta (type I beta) by immunohistochemistry with a monoclonal antibody raised against the alpha-cardiac MHCI alpha. When stained for mATPase after acid and alkaline preincubations, some type I alpha fibres resembled type I beta and type IIA fibres, respectively. Some type I alpha fibres displayed dissimilar mATPase staining, indicating heterogeneity of this fibre population. The appearance of numerous type I alpha fibres in stimulated muscles, which in addition contain type IIA and type I beta fibres, suggested that they may be interspaced between types IIA and I beta. Electrophoresis under nondenaturing conditions disclosed an additional isomyosin both in normal diaphragm and stimulated muscles. This band displayed the same mobility as the slowest isomyosin in rabbit masseter muscle. It was recognized by the same monoclonal (anti-alpha-cardiac MHC) antibody used for immunohistochemistry. Therefore, this isomyosin appeared to be very similar, but perhaps not identical to the alpha-cardiac MHC-based isomyosin, probably resulting from discrete differences in the MHC complement. This assumption agrees with additional findings suggesting an even greater heterogeneity of the MHCs than generally assumed. In support of this, we show in atrium and masseter muscles the existence of an additional, electrophoretically distinct MHC isoform which migrates in close vicinity to MHCI alpha.

Slow-to-fast transitions in myosin expression of rat soleus muscle by phasic high-frequency stimulation.

Denervated soleus muscles of euthyroid and hyperthyroid rats were exposed to phasic high-frequency stimulation for periods of up to 40 days and analysed for their myosin heavy chain (MHC) composition. Denervation alone induced appreciable amounts of the fast MHCIId/x and minute amounts of MHCIIb. However, the effects of phasic high-frequency stimulation exceeded by far those of denervation, leading to marked increases of these two isoforms, as well as to pronounced decreases in slow MHCI. In addition, the present study suggested a greater impact of neural activity on myosin expression than thyroid hormone.

Effects of beta-guanidinopropionic acid-feeding on the patterns of myosin isoforms in rat fast-twitch muscle.

Administration of beta-guanidinopropionic acid (beta-GPA) to rats as 1% of their diet for 6 weeks led to an accumulation of beta-GPA and beta-GPA-phosphate and to a depletion of creatine and phosphocreatine in the fast-twitch plantaris muscle. Adenosine triphosphate concentration was also decreased. Electrophoretic analyses were performed to investigate the effects of beta-GPA on the patterns of fast (FM) and slow (SM) isomyosins, myosin heavy chain (HC) isoforms and myosin light chain (LC) isoforms. The relative concentrations of fast isomyosins FM1 and FM2 decreased, whereas slow isomyosin SM increased. The increase in slow isomyosin corresponded to an increase in the relative concentration of the slow myosin HCI. The changes of the myosin light chain pattern consisted of increases in the relative concentrations of the two slow isoforms, LC1sb and LC2s, and decreases in the fast isoforms LC2f and LC3f. These results demonstrate that beta-GPA administration, leading to a depletion in energy-rich phosphates and a reduced phosphorylation potential, has an impact on myosin isoform expression in rat fast-twitch skeletal muscle.

Isomyosin patterns of single type IIB, IID and IIA fibres from rabbit skeletal muscle.

The present study demonstrates for the first time isomyosin patterns of the three fast-twitch fibre types IIB, IID/X, and IIA. Single muscle fibres were dissected from freeze-dried fibre bundles of rabbit adductor magnus, extensor digitorum longus, and psoas muscles. Pure fibre types, expressing only one myosin heavy chain isoform (MHCIIb, MHCIId/x, MHCIIa), were delineated by electrophoresis of fibre fragments under denaturing conditions. Pieces of the same fibres were then subjected to electrophoresis under non-denaturing conditions. A three-band pattern of fast isomyosins, representing the LC3f homodimer (FM1), the LC1f/LC3f heterodimer (FM2), and the LC1f homodimer (FM3), was detected in each of the three pure fibre types. Therefore, three isomyosins, different in their light chain complement, coexist in each pure fibre. The relative mobilities of the three bands, migrating in the order FM1 > FM2 > FM3, were the same in the three fibre types. The absolute electrophoretic mobilities of the MHCIIb-, MHCIId- and MHCIIa-based isomyosin triplets differed in the order MHCIIb triplets > MHCIId triplets > MHCIIa triplets. The proportions of FM1, FM2, and FM3 varied in type IIB, IID, and IIA fibres. FM2 was the dominant isomyosin in all three fibre types, but fibre type-related differences existed in the FM1 to FM3 ratio. This ratio was lowest in IIA fibres and highest in IIB fibres which agrees with our previous observations that the LC3f/(LC1f + LC3f) fraction is lowest in type IIA and highest in type IIB fibres.

Patterns of myosin isoforms in mammalian skeletal muscle fibres.

The present article attempts to combine existing information on the distribution of fast and slow myosin isoforms in histochemically distinct muscle fibres. Four myosin heavy chain (MHC) isoforms, MHCI, MHCIIa, MHCIIb, and MHCIId(x), have been identified in small mammals and have been assigned to the histochemically defined fibre types I, IIA, IIB, and IID(X), respectively. These fibres express only one MHC isoform and are called pure fibre types. Hybrid fibres expressing two MHC isoforms are regarded as transitory between respective pure fibre types. The existence of pure and hybrid fibres even in normal muscles under steady state conditions creates a spectrum of fibre types. The multiplicity of fibre types is even greater when myosin light chains are taken into account. A large number of isomyosins results from the combinatorial patterns of various myosin light and heavy chains isoforms, further increasing the diversity of muscle fibres. As shown by comparative studies, the distribution of different fibre types varies in a muscle-specific, as well as a species-specific manner.

The histochemical profiles of fast fiber types IIB, IID, and IIA in skeletal muscles of mouse, rat, and rabbit.

This study characterized histochemically three fast fiber types (IIB, IID, IIA) in skeletal muscles of mouse, rat, and rabbit, with special reference to fiber types IIB and IID. The results are complemented by biochemical analyses of myosin heavy chain composition in these muscles. Fiber type delineation is based on various methods for mATPase staining with pre-incubations and assays under different conditions. In rat and mouse, IIB and IID fibers can be best distinguished according to their different mATPase stabilities towards formaldehyde and alkaline pH. In rabbit, the method of Matoba and Gollnick using acid pre-incubation provided best and most reproducible results. In addition to their different mATPase stabilities, the three fast fiber types differ with regard to their oxidative capacities and cross-sectional fiber areas in the three species. In general, Type IIB fibers are the largest and least oxidative, Type IIA fibers the smallest and most oxidative, and Type IID fibers intermediate. In rabbit, Type IID fibers are the predominant fast fiber population in extensor digitorum longus, psoas, and tibialis anterior muscles. As judged from histochemistry, these muscles of rabbit do not contain pure Type IIB fibers. This is in accordance with biochemical results that show the HCIId to form the majority of the myosin heavy chain complement expressed in these muscles. On the other hand, IIB fibers are numerous in rabbit adductor magnus, gastrocnemius, and vastus lateralis muscles. Similarly, appreciable amounts of myosin heavy chain HCIIb are found in the three latter muscles of rabbit.

Fast myosin heavy chain diversity in skeletal muscles of the rabbit: heavy chain IId, not IIb predominates.

The myosin heavy chain (HC) composition of various rabbit muscles was analysed at both the mRNA and the protein level. S1-nuclease mapping was performed with a cDNA probe specific for myosin HCIIa, yielding a fully protected sequence for HCIIa, a partially protected sequence for HCIIb, and an additional signal putatively assigned to HCIId. At the protein level, three fast myosin HC isoforms, HCIIa, HCIIb and HCIId, were separated by gradient PAGE. The results obtained at the protein level were in agreement with the findings at the mRNA level. The expression of appreciable amounts of myosin HCIIb, the predominating isoform of fast-twitch muscles in rat and mouse, was restricted in the rabbit to only a few muscles, i.e. adductor magnus, gastrocnemius, latissimus dorsi and vastus lateralis. Typical fast-twitch muscles such as extensor digitorum longus, tibialis anterior and psoas contained only minute amounts of HCIIb. The HCIId isoform, demonstrated in the present study for the first time in rabbit, is the predominating fast myosin HC isoform in this species. Electrophoretic analyses of myosin HC in histochemically defined single fibers confirmed the lack of fibers expressing only HCIIb in tibialis anterior, whereas such fibers were found in the adductor magnus. In addition to fiber types IIB, IID, and IIA expressing HCIIb, HCIId, and HCIIa, respectively, an appreciable amount of hybrid fibers coexpressing two HC isoforms at various ratios were found: HCIIb > HCIId; HCIId > HCIIb; HCIId > HCIIa; HCIIa > HCIId; HCIIa > HCI; HCI > HCIIa. This fiber-type spectrum indicates possible fiber-type transitions in the order IIB<==> IIB<==>IIDB<==>IID<==>IIDA<==>IIAD<==>IIA<==>IIC<==>IC <==>I.