The role of growth factors in wound healing

Growth factors are mediators with essential importance for undisturbed repair process after wounding. The well coordinated concert of these substances is necessary for healing with complete restoration of function and morphology. These complex mechanisms are disturbed during secondary and delayed repair. The result is protracted healing course and inferior scar quality--either hypo- or hypertrophic. Local and systemic application of these growth factors seems to add important instruments for therapeutic use in the treatment of chronic wounds. Knowledge from experimental research is encouraging, although the exact mechanisms of synergistic action are not completely understood. However, the results from clinical use in controlled studies do not meet these expectations by far. The main reasons for this dilemma are thought to be little understanding in the complex interactions of these substances. In fact, different wound entities seem to reveal different cytokine profiles during the course of repair. Further intensive research therefore is required for the rational use of growth factors in the clinical setting.     

Less than 80% of absorbed iron is promptly incorporated into erythrocytes of infants

Erythrocyte incorporation of an administered iron isotope has been used as a surrogate for iron retention on the assumption (validated in normal and iron-deficient adults) that 80-100% of the retained isotope is promptly incorporated into circulating erythrocytes. This assumption has not been validated in infants or children. The purpose of our study was to determine concurrently in normal infants absorption and erythrocyte incorporation of the stable isotope, (58)Fe. In a preliminary study (Study 1), we demonstrated that fecal excretion of ingested isotope occurs predominantly during the first 4 d after administration but continues beyond 7 d after ingestion, that is, beyond the point at which isotope in feces can be explained either by excretion of isotope that failed to enter enterocytes or by exfoliation of isotope-enriched enterocytes. In Study 2, we administered (58)Fe to nine younger (age 20-69 d) and nine older (age 165-215 d) term infants and collected feces for 11 d. Geometric mean retention of (58)Fe by the younger infants was 31.2% of intake at 4 d and 26.9% at 11 d, and by the older infants, 35.0% at 4 d and 32.5% at 11 d. Erythrocyte incorporation of (58)Fe 14 d after ingestion was 5.2% of the dose by the younger infants and 12.5% by the older infants. Utilization of retained (11 d) isotope thus was 19.8% by the younger infants and 38.3% by the older infants. We conclude that far less than 80% of retained isotope is promptly incorporated into erythrocytes (utilized) by infants.     

Reduction of clinically manifest colorectal cancer by endoscopic screening: empirical evaluation and comparison of screening at various ages.

Endoscopic screening (sigmoidoscopy, colonoscopy) with removal of precancerous lesions can prevent a large proportion of colorectal cancers (CRCs). However, there is lack of data regarding optimal age, time intervals and numbers of screening examinations. We developed and applied modified techniques of epidemiological analysis to evaluate the impact of various endoscopy-based screening strategies on prevention of clinically manifest CRCs between the ages of 50 and 79 in a population-based case-control study (294 cases, 254 controls) conducted in Saarland, Germany. We found a strong potential for reduction of CRC occurrence even with a single screening endoscopy. The optimal age for a single screening endoscopy appears to be around 55 (estimated potential for prevention of cases between the ages of 55 and 79 in case of 100% compliance: 77% (95% confidence interval (CI) 46-90%)). A single screening endoscopy at age 50 would have a lower impact due to failure to prevent CRC at higher ages. Similarly, screening at ages 60 or older would have a lower impact because it would fail to prevent CRC at lower ages. Repeated offers of screening examinations could provide substantial additional benefit with the levels of compliance to be expected in practice, but they would have to be weighed against the increased risks and costs.     

Effects of potassium channel inhibitors on the relaxation induced by the nitric oxide donor diethylamine nitric oxide in isolated human cerebral arteries

OBJECT: The goal of this study was to investigate whether K+ channels are involved in nitric oxide (NO)-induced relaxation of isolated human cerebral arteries. METHODS: Successive concentration-response curves relating to the use of the NO donor diethylamine NO (DEA/NO) were established in the absence and presence of different K+ channel inhibitors after mounting human cerebral arteries onto a wire myograph. The arteries were obtained from macroscopically intact tissue that had been removed during brain tumor operations. A high K+ concentration partially inhibited the relaxant effects of DEA/NO. Different K+ channel inhibitors (tetraethylammonium [TEA], 10(-3) M; charybdotoxin, 10(-7) M; glibenclamide, 10(-6) M; 4-aminopyridine [4-AP], 10(-3) M; BaCl2, 5 x 10(-5) M; and apamin, 10(-6) M) alone failed to affect the responses to DEA/NO. However, a combination of TEA, glibenclamide, 4-AP, and BaCl2 partially blocked the relaxant effects of DEA/NO. In addition, the effects of DEA/NO were inhibited by the thromboxane A2 analog U46619 (3 x 10(-7) M). CONCLUSIONS: Inhibitors of the large-conductance or small-conductance Ca++-activated K+ channels, the adenosine triphosphate-sensitive K+ channels, and the delayed-rectifier or inward-rectifier K+ channels failed to alter the effects of DEA/NO when only one K+ channel blocker was used. However, a regimen of a combination of K+ channel blockers that possess selectivity for different channels demonstrated that different K+ channel types are involved; these channels may function in a redundant manner and compensate for each other. Selective thromboxane A2 agonists are capable of inhibiting the relaxant response to the NO donor.     

Getting the most out of your IP--patent management along its life cycle

Effectively managing and optimizing the value of the patent portfolio is a major challenge for many firms, especially those in knowledge intensive industries, such as the pharmaceutical, biotechnological and chemical industry. However, insights on effective patent portfolio strategies are rare. Therefore, in this article we investigate in detail how firms successfully manage and optimize their patent portfolios to increase their overall competitiveness. We discover that successful patent portfolio management is rooted in managing the patents along their life cycles. Based on the findings of ten case studies, we develop a holistic patent life cycle management model reflecting five distinctive phases of patent management: explore, generate, protect, optimize and decline. We conclude with how our findings can be used in practice.     

Celebrating the 30th Anniversary of Genetic Epidemiology: How to Define Our Scope?†

We review the scope of the scientific discipline genetic epidemiology by considering the steps of genetic epidemiologic research. Starting from the classical definition of genetic epidemiology as provided by Morton and Chung [1978, ISBN‐13: 9780125080507], we propose a slightly modernized definition of the term genetic epidemiology.     

Pathogenesis of West Nile Virus Lineage 2 in Domestic Geese after Experimental Infection

West Nile virus (WNV) is an emerging infectious pathogen circulating between mosquitoes and birds but also infecting mammals. WNV has become autochthonous in Germany, causing striking mortality rates in avifauna and occasional diseases in humans and horses. We therefore wanted to assess the possible role of free-ranging poultry in the WNV transmission cycle and infected 15 goslings with WNV lineage 2 (German isolate). The geese were monitored daily and sampled regularly to determine viremia, viral shedding, and antibody development by molecular and serological methods. Geese were euthanized at various time points post-infection (pi). All infected geese developed variable degrees of viremia from day 1 to day 10 (maximum) and actively shed virus from days 2 to 7 post-infection. Depending on the time of death, the WN viral genome was detected in all examined tissue samples in at least one individual by RT-qPCR and viable virus was even re-isolated, except for in the liver. Pathomorphological lesions as well as immunohistochemically detectable viral antigens were found mainly in the brain. Furthermore, all of the geese seroconverted 6 days pi at the latest. In conclusion, geese are presumably not functioning as important amplifying hosts but are suitable sentinel animals for WNV surveillance.     

A Positron Emission Tomograph based on LSO-APD modules with a sampling ADC read-out system for a students’ advanced laboratory course

A one-day laboratory course on positron emission tomography (PET) for the education of physics students and PhD students in medical physics has been set up. In the course, the physical background and the principles of a PET scanner are introduced. Course attendees set the system in operation, calibrate it using a ²²Na point source and reconstruct different source geometries filled with ¹⁸F. The PET scanner features an individual channel read-out of 96 lutetium oxyorthosilicate (LSO) scintillator crystals coupled to avalanche photodiodes (APD). The analog data of each APD are digitized by fast sampling analog to digital converters (SADC) and processed within field programmable gate arrays (FPGA) to extract amplitudes and time stamps. All SADCs are continuously sampling with a precise rate of 80 MHz, which is synchronous for the whole system. The data is transmitted via USB to a Linux PC, where further processing and the image reconstruction are performed. The course attendees get an insight into detector techniques, modern read-out electronics, data acquisition and PET image reconstruction. In addition, a short introduction to some common software applications used in particle and high energy physics is part of the course.