Neurodegenerative Diseases of the Retina and Potential for Protection and Recovery

Recent advances in our understanding of the mechanisms in the cascade of events resulting in retinal cell death in ocular pathologies like glaucoma, diabetic retinopathy and age-related macular degeneration led to the common descriptive term of neurodegenerative diseases of the retina. The final common pathophysiologic pathway of these diseases includes a particular form of metabolic stress, resulting in an insufficient supply of nutrients to the respective target structures (optic nerve head, retina). During metabolic stress, glutamate is released initiating the death of neurones containing ionotropic glutamate (N-methyl-D-aspartat, NMDA) receptors present on ganglion cells and a specific type of amacrine cells. Experimental studies demonstrate that several drugs reduce or prevent the death of retinal neurones deficient of nutrients. These agents generally block NMDA receptors to prevent the action of glutamate or halt the subsequent pathophysiologic cycle resulting in cell death. The major causes for cell death following activation of NMDA receptors are the influx of calcium and sodium into cells, the generation of free radicals linked to the formation of advanced glycation endproducts (AGEs) and/or advanced lipoxidation endproducts (ALEs) as well as defects in the mitochondrial respiratory chain. Substances preventing these cytotoxic events are considered to be potentially neuroprotective

Quality of Life and Long-term Results After Ruptured Abdominal Aortic Aneurysm

AbstractObjectives. Quality of life as an endpoint of surgery and the long-term prognosis for patients who have survived surgery for a ruptured abdominal aortic aneurysm (RAAA) is not well-documented.Patients and methods. The records of all patients from 1993 to 2000 who underwent resection of RAAA were reviewed. Survival data were calculated from direct contact with the patients or follow-up records. All patients who were alive at the time of our study were invited to participate in follow-up investigations. They received the internationally comparable WHO-QOL-BREF-test.Results. In a period of 7 years, 80 patients underwent surgery for RAAA. The average follow-up time was 5.1 years (1–7.9 years). Our data show that 51% of our patients died within 6 months postoperatively because of the complications of the aortic rupture (in-hospital mortality 39%). Patients who survived the first 6 months after surgery died for the same reasons as the normal population. However, patients who were younger than 75 at the time of RAAA had a higher relative survival rate than a matched sample of the population. There was no significant difference in the quality of life between the study group and the general population.Conclusions. RAAA survivors had no difference in long-term survival as compared to the general population and also had very few long-term complications. The WHOQOL-BREF-test suggests that the quality of life of survivors of RAAA is similar to the general population

Presence of Borrelia burgdorferi sensu lato antibodies in the serum of patients with abdominal aortic aneurysms

Infectious agents are likely to play a role in the pathogenesis of chronic inflammatory diseases, including abdominal aortic aneurysms (AAAs). The goal of this study was to determine if Borrelia burgdorferi sensu lato (sl), a microorganism responsible for Lyme disease, is involved in the etiology of AAAs. The presence of serum antibodies against B. burgdorferi sl was measured with enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blotting in 96 AAA and 108 peripheral artery disease (PAD) patients. Polymerase chain reaction (PCR) was used for the detection of Borrelia-specific DNA in the aneurysm wall. Among AAA patients 34% and among PAD patients 16% were seropositive for B. burgdorferi sl antibodies (Fisher’s exact test, p = 0.003; odds ratio [OR] 2.79; 95% confidence interval [CI] 1.37–5.85). In the German general population, 3–17% are seropositive for Borrelia antibodies. No Borrelia DNA was detected in the aneurysm wall. Our findings suggest a relationship between AAAs and B. burgdorferi sl. We hypothesize that the underlying mechanism for B. burgdorferi sl in AAA formation is similar to that by the spirochete Treponema pallidum; alternatively, AAAs could develop due to induced autoimmunity via molecular mimicry due to similarities between some of the B. burgdorferi sl proteins and aortic proteins

Diversified actin protrusions promote environmental exploration but are dispensable for locomotion of leukocytes

Most migrating cells extrude their front by the force of actin polymerization. Polymerization requires an initial nucleation step, which is mediated by factors establishing either parallel filaments in the case of filopodia or branched filaments that form the branched lamellipodial network. Branches are considered essential for regular cell motility and are initiated by the Arp2/3 complex, which in turn is activated by nucleation-promoting factors of the WASP and WAVE families. Here we employed rapid amoeboid crawling leukocytes and found that deletion of the WAVE complex eliminated actin branching and thus lamellipodia formation. The cells were left with parallel filaments at the leading edge, which translated, depending on the differentiation status of the cell, into a unipolar pointed cell shape or cells with multiple filopodia. Remarkably, unipolar cells migrated with increased speed and enormous directional persistence, while they were unable to turn towards chemotactic gradients. Cells with multiple filopodia retained chemotactic activity but their migration was progressively impaired with increasing geometrical complexity of the extracellular environment. These findings establish that diversified leading edge protrusions serve as explorative structures while they slow down actual locomotion