[Networking, Coordination and Responsibilities based on Health Regionsplus: New Health Political Approaches and Developments in Bavaria]. / Vernetzung, Koordination und Verantwortung durch Gesundheitsregionenplus: Neue gesundheitspolitische Ansätze und Entwicklungen in Bayern.

For many health and health-care problems in the population, there is a need for professional management and coordination instruments as well as a competent local network. The new "Health Regionsplus" in Bavaria offer such a structure. This new concept is presented in the following article. The "Health Regionsplus" aim to improve the population's health, the health-related quality of life, equity in health, as well as to further develop the local health care. The Bavarian State Ministry of Health and Care will support up to 24 regions with a funding of up to 50 000 Euro yearly per "Health Regionplus" until the end of 2019. The structure of "Health Regionsplus" implies the establishment of a coordinating agency that works as a "motor", a health forum on the strategic level and relevant working groups. "Health Regionsplus" involve all relevant stakeholders of the regional health system and are chaired by the district administrator or mayor. They work primarily in the fields of health care and prevention/health promotion but can also pursue other region-specific fields. The Bavarian Health and Food Safety Authority supports and evaluates the "Health Regionsplus". There is also a coordinating office which organises the exchange of information and experience among the "Health Regionsplus". Although such a comprehensive regional approach does not change the statutory decision-making structures and responsibilities it does offer the communities an instrument to involve local needs in their decision-making processes.

Development of a skin-friendly microemulsion for dermal allergen-specific immunotherapy.

Due to their role in immune responses, the skin dendritic cells (i.e. epidermal Langerhans cells and dermal dendritic cells) have become of great interest to researchers in the past decades. A dermal administration of allergens could target these professional antigen-presenting cells directly and build up immunotolerance. Additionally, many of the adverse side effects, which are seen in the current state of the art specific immunotherapy routes, could be avoided. Therefore, in this study a penetration enhancing microemulsion was developed and its physicochemical properties were determined under several storage conditions. The influence of different preservatives on the microemulsion stability was observed. We examined epidermal penetration of Alexa Fluor-647 labelled bee-venom phospholipase A2 (Api m 1) using the Franz diffusion cell set up and confocal laser-scanning microscopy. First results of an in-vivo Api m 1-allergic mouse model indicated the protective efficacy of dermal AIT with our newly developed microemulsion. Summarily, the developed microemulsion is a suitable, stable drug delivery system for the topical administration of proteogenic allergens into the epidermis and is able to reach dendritic cells in the skin.

At the onset of transformation polyomavirus middle-T recruits shc and src to a perinuclear compartment coincident with condensation of endosomes.

To examine the early cellular changes that accompany transformation, middle-T antigen (the transforming protein of polyomavirus), was expressed from an inducible promoter in Rat2 fibroblasts and in normal diploid human fibroblast (MRC5) cells using a replication defective adenovirus vector. The earliest detectable expression of middle-T antigen correlated closely with the initial changes in cellular morphology. At this time, expression of middle-T antigen resulted in the redistribution of shc and src to a brefeldin A resistant perinuclear compartment coincident with the formation of kinase active complexes containing middle-T antigen, shc and src. The first detectable changes directly related to altered morphology was reorganization of actin filaments, and the condensation of tubular endosomes in the perinuclear region of the cell. These results suggest a potential role for perinuclear localized mT molecules in some of the morphologic changes associated with the initial phase of cellular transformation.

Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils.

The subcellular location of taurine, and its precursor, hypotaurine, within human neutrophils has been examined by nitrogen cavitation, Percoll-gradient centrifugation and HPLC analysis. Hypotaurine and taurine were found to reside within the cytosolic compartment of the cell. The ratio of taurine to hypotaurine is approx 50:1. The cytosolic concentration of taurine is approx. 50 mM. The concentration of hypotaurine decreased by 80% when resting neutrophils were converted into actively respiring cells by exposure to opsonized zymosan. These results prompted in vitro studies on the antioxidant properties of hypotaurine. We demonstrate by EPR spectroscopy that hypotaurine competes with 5,5'-dimethyl-1-pyrroline N-oxide) (DMPO) for hydroxyl radicals, and that it is the sulfinyl group which confers hydroxyl radical scavenging activity to it. Following its exposure to hydroxyl radicals, two oxidation products were isolated by HPLC, one of which has been identified as taurine. The biological roles of hypotaurine and taurine in the neutrophil are discussed with respect to their antioxidant properties and subcellular location within the cell.

Myeloperoxidase oxidation of sulfur-centered and benzoic acid hydroxyl radical scavengers.

Myeloperoxidase (MPO) oxidizes sulfur-centered and benzoate hydroxyl radical scavengers through formation of HOCl. Sulfur-centered hydroxyl radical scavengers compete with benzoate as antioxidants of HOCl. We conclude from these observations that competition experiments between benzoate and sulfur-centered hydroxyl radical scavengers are not sufficiently specific to infer participation of hydroxyl radicals in oxidative reactions mediated by neutrophils because of the unique action of MPO in affecting oxidation of the test radical scavengers.

Comment on "30,000-year-old wild flax fibers".

Kvavadze et al. (Brevia, 11 September 2009, p. 1359) identified fiber samples as 30,000-year-old flax based on a comparison with modern flax fibers analyzed by compound microscope and on the presence of dislocations/nodes in the fibers. We argue that this evidence is not sufficient to identify the fibers as flax.

[Cost-benefit analysis of the use of rhBMP-2 in open tibial fractures: savings from a health insurer's perspective]. / Kosten-Nutzen-Betrachtung des Einsatzes von rhBMP-2 bei offenen Tibiafrakturen: Nettoeinsparungen aus Krankenkassensicht erzielbar.

BACKGROUND AND PURPOSE: The purpose of the current study was to evaluate savings from the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in open tibia fractures by faster fracture healing and reduction of secondary treatment costs from a health insurance perspective for Germany and to compare them to the upfront price of 2900 EUR of rhBMP-2. METHODS: Raw data from a previously published study (BESTT study) were used to conduct an economic calculation for secondary treatment costs for each patient from the standard care group and the 1.5 mg/ml rhBMP-2 group based on G-DRG 2005 prices from a health insurer's perspective for an observation period of 1 year for Germany. RESULTS: The use of rhBMP-2 leads to savings of 5697 EUR and 3183 EUR per patient for Gustilo-Anderson grade IIIB and all grade IIIA and B injuries, respectively. These savings offset the upfront price of 2900 EUR of rhBMP-2 and, therefore, net savings of 2797 EUR and 283 EUR for grade IIIB and all grade IIIA and B injuries can be achieved, respectively. These savings are mainly due to reduced sickness payments because of faster fracture healing in the rhBMP-2 group. CONCLUSIONS: The current study shows that the use of rhBMP-2 in Gustilo-Anderson grade IIIA and B open fractures leads--besides the better medical outcome for patients as shown previously in the BESTT study--to net savings from a health insurer's perspective.

[Health-economic considerations for the use of BMP-2 for spinal surgery in Germany]. / Gesundheitsökonomische Uberlegungen für den Einsatz des Knochenwachstumsfaktors BMP-2 in der Wirbelsäulenchirurgie für das deutsche Gesundheitssystem.

INTRODUCTION: BMP-2 can replace autogenous bone grafting in lumbar one-level anterior lumbar interbody fusions (ALIF). The current G-DRG system does not reimburse the upfront price of 2,970 euro per BMP-2 application for hospitals in Germany. The purpose of the current study was to create a health economic model to evaluate the financial savings for health care providers (hospitals) and health care payers (health care insurance) that can be achieved by the use of BMP-2 in spine surgery. METHODS: A previously published pooled data analysis was used in which BMP-2 showed significant improvements in the treatment after ALIF surgery compared to autogenous bone grafting, including earlier return to work time and reduced revision rates. These medical findings were transformed into economic data based on the regulations of the German health system of 2005. RESULTS: The significantly shorter return to work time under BMP-2 treatment generates important financial savings for health care insurances offsetting the upfront prize of 2,970 euro for BMP-2. Savings for hospitals are mainly related to shorter surgery time due to the absence of the bone grafting procedure and faster discharge of the patient. CONCLUSIONS: The combination of improved medical outcome by BMP-2 treatment for the patient and net savings for the entire health care system in Germany represents a "dominant" strategy from a health economic perspective. This implicates that BMP-2 in ALIF procedures is to be recommended from a health economic point of view for the German health care system.

Mitogenic stimulation of HeLa cells increases the activity of the anoxic stress protein, LDH 6/k: suppression by queuine.

Mitogenic stimulation of quiescent mammalian cells triggers an array of early events crucial for cell cycle progression. Here we show that the activity of the anoxic stress protein, lactate dehydrogenase 6/k, transiently increased after mitogenic stimulation of serum-starved HeLa cells. Regulation of lactate dehydrogenase 6/k activity in early G1 depended on the activity of a receptor tyrosine kinase and on protein and mRNA synthesis, but did not involve protein kinase C. The guanine analog, queuine, an ubiquitously occurring tRNA base of bacterial origin, suppressed the mitogen-induced protein synthesis and also the transient increase in lactate dehydrogenase 6/k activity. The results suggest that queuine relieves hypoxic stress resulting from mitogenic stimulation by suppressing protein synthesis during G0/G1 transition.

A certain fate: spread of HIV among young injecting drug users in Manipur, north-east India.

This study aimed to measure risk behaviours and seroprevalence of HIV and hepatitis C virus in IDUs in Manipur, North-East India, and evaluate the impact of the recently established Syringe and Needle Exchange Program (SNEP). Sampling strategy was based on social networks. Peer interviewers administered the study questionnaire and collected blood for anti-HCV and anti-HIV testing. One hundred and ninety-one IDUs (85% male) took part. Average age at first injection was 19 years and average length of time injecting was 3.7 years. The main drug currently injected was heroin (66%). Most (93%) reported having shared injecting equipment and only 42% had used the SNEP. Three-quarters (74.7%) were infected with HIV and almost all (98%) with HCV. Age (p < 0.001) and length of time injecting (p < 0.001) were significantly associated with being HIV-positive. Over two-thirds were sexually active, but only 3% consistently used condoms. Almost three-quarters of IDUs in this study were infected with HIV, most within the first two years of injecting, indicating infection continues to spread at very high rates. Unsafe sexual practices place partners of infected IDUs at risk of infection. The SNEP must increase its coverage to young and new IDUs before they are exposed to blood-borne viruses.

The sequential effects of estrogen administration and hypertension on cardiac function in ewes.

OBJECTIVE: Our objective was to study the effect of estrogen administration and moderate hypertension on left ventricular size, pump function, and contractility in chronically instrumented ewes. STUDY DESIGN: Ewes were either given 0.06 mg/kg 17beta-estradiol intramuscularly (n = 8) or were made hypertensive (n = 6) by inflation of an occluder around the aorta and were studied weekly. After 3 weeks each ewe received the opposite treatment. RESULTS: Estrogen administration caused an increase in left ventricular chamber size at a given pressure, fractional shortening (21.9% +/- 2.9% to 28.5% +/- 3.7%), and stroke volume (1.4 +/- 0.3 mL/kg to 1.6 +/- 0.3 mL/kg). Subsequent hypertension further increased left ventricular size at a given pressure but decreased fractional shortening (20.0% +/- 4.4%) and stroke volume (1.3 +/- 0.3 mL/kg). With hypertension first, there was no left ventricular enlargement, even with subsequent estrogen administration, and there were no changes in left ventricular pump function. End-systolic pressure and stress-dimension relationships did not change with either treatment. The end-systolic wall stress-fractional shortening relationship was likewise unchanged, suggesting that neither treatment changed contractility. CONCLUSIONS: The left ventricle previously exposed to hypertension does not remodel when exposed to estrogen, and cardiac pump function decreases when the estrogen enlarged heart is faced with moderate, subacute hypertension.