[E-cigarettes: toxicological fiasco or better than not giving up smoking?] / E-Zigaretten ­ toxikologisches Fiasko oder besser als kein Rauchstopp?

E­cigarettes are increasingly used to replace tobacco cigarettes and to stop smoking, but mainly in the sense of dual use. There is lively debate about the assessment of the health risks of e­cigarettes, but so far there are no comprehensive data for direct comparison with tobacco cigarettes. Other points of controversy include the potential for smoking cessation and the risk of moving from e­cigarettes to tobacco cigarettes (gateway hypothesis). The present overview comes to the conclusion that, in accordance with the health policy already largely implemented in Great Britain, e­cigarettes represent a greatly reduced health risk compared with tobacco cigarettes and are certainly suitable for giving up smoking.

[Expenditure on the Care of COPD Patients Under Everyday Conditions in Pneumological Practices Differentiated According to Patients in Chronic Care and New Patients and Severity of the Illness]. / Aufwand bei der Betreuung von COPD-Patienten unter Alltagsbedingungen in pneumologischen Praxen differenziert nach bekannten und neuen Patienten und nach Schweregraden der Erkrankung.

New patients in the secondary respiratory care require more time for the first consultation and place a higher diagnostic and therapeutic demand if compared to patients already in chronic care. More diagnostic procedures and patient's education by the team are required. No such burden is observed regarding differential degrees of severity of respiratory diseases, e. g. COPD. The overall demands add up to twice the demands of patients already in care. Thus the time required for the treatment of 50 new patients allows consultations for 100 patients already known in the office.As additional time and effort for new patients is not adequately represented in the German medical tax (EBM) a trend to risk selection and a preference for control patients is observed. In contrast incentives to foster treatment of new patients could be an effective measure to dramatically reduce waiting time for visits with pulmonologists. This should be achieved by changes in the German medical tax (EBM).

[The Aut-idem Rule and the Importance of Patient-Individual Selection of Inhalers for the Therapy of Airway Diseases in Practices of Pneumologists and General Practitioners - Assessment and Implementation by Pneumologists and General Practitioners]. / Aut-idem-Regelung und Inhalatorauswahl bei inhalativer Therapie in pneumologischen und hausärztlichen Praxen unter Alltagsbedingungen ­ Einschätzung und Umsetzung durch Pneumologen und Hausärzte.

Drug therapy of obstructive airway diseases mainly relies on inhaled medication. The success of this therapy depends primarily on the selection of the appropriate inhaler considering patient's choice and the correct application. The aut-idem-rule, an active exclusion of the optional substitution by the pharmacist, allows prescribing physicians to ensure the delivery of a particular inhaler, which was selected for that patient, who was trained to use specifically that inhaler. This survey shows that pneumologists and, to a greater extent general practitioners, do not consistently make use of this option, although they unanimously agree on the importance of targeted inhaler selection. As a result, patients may receive different inhalers in the pharmacy, where the inhaler is chosen under consideration of market-driven aspects such as rebate contracts or stock. This causes that patients get confused by the exchange of their inhaler. Thus the exchange of the inhaler by the pharmacist leads to uncertainty and application problems in patients. Hence, the success of the comparatively complex inhaled therapy is endangered. This could be prevented, if prescribing physicians were informed and supported consistently regarding the use of aut-idem exclusion to ensure an optimal therapy for each individual patient.

[The Patient Questionnaire "Monitoring of Exacerbation Probability (MEP)"]. / Das Patienten-Questionnnaire "Monitoring of Exacerbation Probability (MEP)".

Exacerbations determine the disease process in COPD often decisively, whereas their detection and documentation has not been established satisfactory yet. For this purpose, a simple short Patient Questionnaire with a maximum of five positive answers was developed and evaluated. Values of 2 or more positive responses amplify the signal for an exacerbation, while with the presence of only 1 positive response a potential, but not a likely exacerbation must be considered. The MEP is well suited for a continuous documentation in computer-based administration systems.

[COPD Classification GOLD I-IV vs. GOLD A-D in Real Life: Comparing Impact on Application, Advantages and Disadvantages]. / Die Klassifikationen GOLD I-IV vs. GOLD A-D in der Alltagsversorgung: Vergleichende Prüfung in Anwendung, Auswirkungen, Vor- und Nachteilen.

COPD patients under shared treatment of general practitioners and pulmonologists were grouped in GOLD classification I-IV and A-D, respectively to find out whether the new A-D classification showed advantages concerning therapy decisions. As a result of CAT separation at 10 points (GOLD A-D rule) group C with higher risk and low symptoms was very small. It is described how CAT threshold values of 15 and 20 points would affect the size of the groups A-D in pulmonary practice. The new A-D classification showed better signals for exacerbations. Regardless of the classification I-IV or A-D respectively patients received a considerable amount of overtreatment (low degrees of severity) or undertreatment (higher degrees of severity). Only the application of prednisolone and of roflumilast, respectively, showed a noticeable relation to increased exacerbations in system A-D. A variety of reasons might cause that obviously the principles of both classifications are followed poorly. Higher attention for exacerbations may be considered as a progress resulting from the new a-d classification. Possible abrupt short term intraindividual changes of severity, inadequate to the global course of disease, are a possible disadvantage of the new A-D classification.

[Real-Life Evaluation of the Compact Program for Smoking Cessation]. / Real-Life-Evaluation des Kompakt-Programmes zur Tabakentwöhnung.

Smoking cessation as a therapeutic intervention has largely not the significance that it should have according to its potential influence on diseases in the pulmonary practice. Barriers against smoking cessation apart from the addiction character of tobacco dependence are mainly the almost complete absence of reimbursement as well as concerns regarding low achievable long-term abstinence. The presented study shows that despite these barriers smoking cessation in pulmonology practice is successful if carried out by using a 2-step motivation of the participants. The long-term abstinence success of 46 % after 12 months (point prevalence) presented here was achieved with the use of behavioral therapy and medical support. Success factors are doctor's office setting and consequent information and encouragement for medical support (mostly varenicline).

[Therapy adherence in bronchial asthma patients: Healthcare under everyday conditions in pulmonological practices]. / Therapieadhärenz bei Asthma bronchiale - Versorgung unter Alltagsbedingungen in der pneumologischen Praxis.

In the present study, patients with asthma were interviewed with regard to their treatment adherence. It was shown that adherence is significantly influenced by age, occupation, quality of information about the disease and interest of the patient in disease, mode of action and use of the inhalation device. Younger, working patients who do not feel "completely adequately" informed are more likely to be not-adherent. Each aspect should be noted separately.The characterization enables forming target groups for appropriate counselling initiatives in pulmonology practice and allows the effectiveness of the measures to be examined. The results confirm the importance of doctor/patient communication for achieving a high level of adherence and thus therapeutic success.It is suggested that, in addition to questionnaires already in use, asthma patients should be given the following questions in writing during routine monitoring of therapy; based on the results of the survey, the extent of advice necessary can be determined -Do you feel sufficiently informed about your illness? -Do you feel sufficiently informed about the effect of the drug therapy? -Do you feel sufficiently informed about the handling of the inhalation drugs? -Are you satisfied with the handling of your inhalation medication? The following options to answer the questions should be available: completely - mainly - somewhat - not at all. There were significant differences in adherence between patients who were completely satisfied with the handling of their device and those that were not. However, there was no significant difference between the devices. Therefore, the same therapy adherence can be predicted for all devices when the device is suitable for the patient and also provides complete satisfaction in handling. Since it is the subjective perception of patients, the data show significant differences between study centres. These were mirrored in a blind benchmark to stimulate improvements.

[Smoking cessation in patients with COPD]. / Tabakentwöhnung bei COPD.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Cigarette smoking is the main cause of COPD. Quitting smoking is thus the most effective treatment strategy and central in COPD prevention. A number of guidelines on prevention, diagnosis, therapy and rehabilitation of COPD have been published. To help implementing and standardizing smoking cessation in COPD a guideline was published 2008 in Germany focusing on this complex issue. The present guideline is an update of the 2008 guideline and has a high grade of evidence (S3 according to the AWMF; Arbeitsgemeinschaft wissenschaftlicher medizinischer Fachgesellschaften). The guideline gives comprehensive and practical information on how to integrate smoking cessation as an central part of COPD therapy.

[Modern medical support for smoking cessation]. / Moderne medikamentöse Unterstützung der Tabakentwöhnung.

In view of the high morbidity and mortality associated with tobacco, smoking cessation is one of the most urgent medical challenges. It is effective when psychosocial support is combined with accompanying medication. In view of the associated rate of occurrence of cardiovascular diseases, COPD/emphysema as well as lung cancer, it is highly cost-effective. The nicotine replacement substances Bupropion and Varenicline used in smoking cessation therapies demonstrate a well-documented increase in effectiveness. Their use is not complicated. An increase in the overall cessation success rate by a factor of 2-3 is obtained when using an accompanying course of medication.

Ascorbate-enhanced chondrogenesis of ATDC5 cells.

The ATDC5 cell line exhibits the multistep chondrogenic differentiation observed during endochondral bone formation. However, it takes up to two months to complete the process of cell expansion, insulin addition to promote differentiation and further changes in culture conditions effectively to induce hypertrophy. We sought to produce consistent chondrogenesis with significant hypertrophic differentiation with simpler conditions in a more practical time period. By adding ascorbate, the prechondrogenic proliferation phase was shortened from 21 to 7 days, with production of cartilaginous nodules during the chondrogenic phase, after insulin addition, that were greater in number and larger in size. Immunohistochemistry indicated much greater matrix elaboration and the mRNA expression of sox9, aggrecan and collagen type II were all significantly increased earlier and to a much higher degree when compared with controls. Moreover, there was a robust induction of hypertrophy: Col10a1, Runx2 and Mmp13 were all induced within 7-10 days. In conclusion, addition of ascorbate to ATDC5 cultures shortened the prechondrogenic proliferation phase, produced earlier chondrogenic differentiation, heightened gene expression and robust hypertrophic differentiation, abrogating the need for extended culture times and the changes in culture conditions. This simple modification considerably enhances the practicality of this cell line for studies of chondrogenesis.

Visible light photooxidation of nitrate: the dawn of a nocturnal radical.

Highly oxidizing nitrate radicals (NO3˙) are easily accessed from readily available nitrate salts by visible light photoredox catalysis using a purely organic dye as the catalyst and oxygen as the terminal oxidant. The interaction of the excited catalyst and nitrate anions was studied by spectroscopic methods to elucidate the mechanism, and the method was applied to the NO3˙ induced oxidation of alkynes and alcohols.

Regulation of chondrocyte gene expression.

Extracellular influences known to affect the regulation of chondrocyte biosynthetic and catabolic activity have been shown to include soluble factors, extracellular matrix and mechanical stress. A balance of these numerous extracellular influences is required for normal function of articular cartilage. It is likely that OA is the result of an imbalance of regulatory influences, ultimately resulting in deleterious changes in gene expression, altered extracellular matrix (ECM) and tissue degeneration. Molecular signaling via soluble mediators has been shown to be crucial to cartilage homeostasis. A number of vitamins, hormones, growth/differentiation factors and cytokines have been implicated in chondrocyte differentiation and cartilage metabolism. During normal maintenance, as well as in aging and pathology, these soluble factors can significantly influence the physical properties and the function of cartilage. Chondrocytes, like cells in other tissues, exist within an information-rich extracellular environment consisting of ECM molecules, a milieu which interacts with and modulates the activity of growth factors, hormones and ECM remodeling enzymes. Cell surface matrix receptors, including a family of proteins known as integrins, connect structural information in the ECM to a complex cellular response mechanism in the cell's interior. Integrins on cell surfaces detect and transduce signals in a cooperative manner with other adhesion receptor classes and/or growth factor receptors. The effects of mechanical stress upon a number of chondrocyte biological parameters has been examined in several laboratories. Other investigations have addressed the mechanism by which mechanical force affects biochemical and biosynthetic processes in chondrocytes, in particular synthesis of aggrecan, a major component of the cartilage ECM. Each of these extracellular influences upon chondrocyte metabolism may affect regulation of chondrocyte ECM biosynthesis at many levels, including mRNA transcription, RNA splicing, nuclear transport, protein translation, post-translational modification, intracellular vesicular transport, and protein secretion. Transcriptional regulation of some of the major protein and proteoglycan components of the cartilage ECM has been examined in a number of species, and promoters have been characterized for aggrecan, link protein and collagen type II genes. There is evidence that gene expression may be altered in OA cartilage, providing clues as to which subsets of genes expressed in chondrocytes may be considered relevant to OA pathophysiology.

Bovine chondrocyte link protein cDNA sequence: interspecies conservation of primary structure and mRNA untranslated regions.

The sequence for bovine link protein cDNA, including 108 bases of the 5' untranslated region (UTR) and 768 nucleotides of the 3' UTR, was determined from polymerase chain reaction products and bovine articular chondrocyte cDNA clones. The deduced primary structure for bovine link protein predicts a protein 354 amino acid residues in length. Comparative analysis with link protein sequence from several other species revealed overall high conservation of protein coding sequence. High nucleotide sequence conservation was observed within the extensive 5' and 3' UTRs of bovine, human, pig, chick and rat link protein mRNA. As evidence that the UTRs might play a role in regulation of link protein mRNA turnover, multiple occurrences of the adenosine-uridine binding factor motif A(Ua)A were found to be conserved between species within 3' UTRs. A polyadenylation signal was conserved between the bovine and chicken sequence, use of which would result in the smallest of multiple bovine link protein mRNA species observed by Northern blot analysis.