[A database of available DNA tests in the dog]

For genetic counseling this report presents a database of canine hereditary diseases and coat color characteristics, which have been solved on the molecular level.The database facilitates access to appropriate diagnostic laboratories for specific phenotypes. The recent decoding of the dog genome provides ideal conditions for the molecular genetic analysis of hereditary traits and diseases. Therefore the authors would like to encourage veterinary surgeons in particular to report cases to assist the molecular analysis of further phenotypes in future.

Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation

The aim of the study was to compare the effect duration of two different protocols of repetitive transcranial magnetic stimulation (rTMS) on saccade triggering. In four experiments, two regions (right frontal eye field (FEF) and vertex) were stimulated using a 1-Hz and a theta burst protocol (three 30Hz pulses repeated at intervals of 100ms). The same number of TMS pulses (600 pulses) was applied with stimulation strength of 80% of the resting motor threshold for hand muscles. Following stimulation the subjects repeatedly performed an oculomotor task using a modified overlap paradigm, and saccade latencies were measured over a period of 60min. The results show that both 1-Hz and theta burst stimulation had inhibitory effects on saccade triggering when applied over the FEF, but not over the vertex. One-hertz rTMS significantly increased saccade latencies over a period of about 8min. After theta burst rTMS, this effect lasted up to 30min. Furthermore, the decay of rTMS effects was protocol-specific: After 1-Hz stimulation, saccade latencies returned to a baseline level much faster than after theta burst stimulation. We speculate that these time course differences represent distinct physiological mechanisms of how TMS interacts with brain function.

Fluorescent microangiography (FMA): an improved tool to visualize the pulmonary microvasculature

Visualization of the complex lung microvasculature and resolution of its three-dimensional architecture remains a difficult experimental challenge. We present a novel fluorescent microscopy technique to visualize both the normal and diseased pulmonary microvasculature. Physiologically relevant pulmonary perfusion conditions were applied using a low-viscosity perfusate infused under continuous airway ventilation. Intensely fluorescent polystyrene microspheres, confined to the vascular space, were imaged through confocal optical sectioning of 200 microm-thick lung sections. We applied this technique to rat lungs and the markedly enhanced depth of field in projected images allowed us to follow vascular branching patterns in both normal lungs and lungs from animals with experimentally induced pulmonary arterial hypertension. In addition, this method allowed complementary immunostaining and identification of cellular components surrounding the blood vessels. Fluorescent microangiography is a widely applicable and quantitative tool for the study of vascular changes in animal models of pulmonary disease.

Annexins sense changes in intracellular pH during hypoxia

The pH(i) (intracellular pH) is an important physiological parameter which is altered during hypoxia and ischaemia, pathological conditions accompanied by a dramatic decrease in pH(i). Sensors of pH(i) include ion transport systems which control intracellular Ca2+ gradients and link changes in pH(i) to functions as diverse as proliferation and apoptosis. The annexins are a protein family characterized by Ca2+-dependent interactions with cellular membranes. Additionally, in vitro evidence points to the existence of pH-dependent, Ca(2+)-independent membrane association of several annexins. We show that hypoxia promotes the interaction of the recombinant annexin A2-S100A10 (p11) and annexin A6 with the plasma membrane. We have investigated in vivo the influence of the pH(i) on the membrane association of human annexins A1, A2, A4, A5 and A6 tagged with fluorescent proteins, and characterized this interaction for endogenous annexins present in smooth muscle and HEK (human embryonic kidney)-293 cells biochemically and by immunofluorescence microscopy. Our results show that annexin A6 and the heterotetramer A2-S100A10 (but not annexins A1, A4 and A5) interact independently of Ca2+ with the plasma membrane at pH 6.2 and 6.6. The dimerization of annexin A2 within the annexin A2-S100A10 complex is essential for the pH-dependent membrane interaction at this pH range. The pH-induced membrane binding of annexins A6 and A2-S100A10 might have consequences for their functions as membrane organizers and channel modulators.

Effects of diabetes mellitus on periodontal and peri-implant conditions: update on associations and risks

OBJECTIVES: To review the evidence for the association between diabetes and periodontal and peri-implant conditions and the impact of periodontal therapy in subjects with diabetes. MATERIAL AND METHODS: A search of MEDLINE-PubMed was performed up to and including December 2007. The search was limited to clinical studies published in English. Publications on animal studies were excluded. The selection criteria included all levels of available evidence. RESULTS: Evidence on the association between diabetes and periodontitis supports the concept of increased severity but not extent of periodontitis in subjects with poorly controlled diabetes. Subjects with controlled diabetes do not show an increase in extent and severity of periodontitis. Periodontitis is associated with poor glycaemic control and diabetes-related complications. It is inconclusive that periodontal therapy with or without the use of antibiotics results in improvements of glycaemic control and of markers of systemic inflammation. Evidence is lacking to indicate that implant therapy in subjects with diabetes yields long-term outcomes comparable with those of non-diabetic subjects. CONCLUSIONS: Poorly controlled diabetes may be considered a risk factor for increased severity of periodontitis. The effects of periodontal therapy on glycaemic control and systemic inflammation is not proven beyond doubt and need to be confirmed in large-scale randomized-controlled clinical trials.

Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions

BACKGROUND: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective. METHODS AND RESULTS: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic lower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic lower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSION: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic lower limb ischemia as well as for regulatory purposes.