Septotemporal variation in modulation of synaptic transmission, paired-pulse ratio and frequency facilitation/depression by adenosine and GABAB receptors in the rat hippocampus.

Short-term synaptic plasticity represents a fundamental mechanism in neural information processing and is regulated by neuromodulators. Here, using field recordings from the CA1 region of adult rat hippocampal slices, we show that excitatory synaptic transmission is suppressed by strong but not moderate activation of adenosine A1 receptors by 2-Chloro-N6-cyclopentyladenosine (CCPA) more in the dorsal than the ventral hippocampus; in contrast, both mild and strong activation of GABAB receptors by baclofen (1 µM, 10 µM) suppress synaptic transmission more in the ventral than the dorsal hippocampus. Using a 10-pulse stimulation train of variable frequency, we found that CCPA modulates short-term synaptic plasticity independently of the suppression of synaptic transmission in both segments of the hippocampus and at stimulation frequencies greater than 10 Hz. However, specifically regarding the paired-pulse ratio (PPR) and frequency facilitation/depression (FF/D) we found significant drug action before but not after adjusting conditioning responses to control levels. Activation of GABABRs by baclofen suppressed synaptic transmission more in the ventral than the dorsal hippocampus. Furthermore, relatively high (10 µM) but not low (1 µM) baclofen concentration enhanced both PPR and FF in both hippocampal segments at stimulation frequencies greater than 1 Hz, independently of the suppression of synaptic transmission by baclofen. These results show that A1Rs and GABABRs control synaptic transmission more effectively in the dorsal and the ventral hippocampus, respectively, and suggest that these receptors modulate PPR and FF/D at different frequency bands of afferent input, in both segments of the hippocampus.

Cardiovascular Effects of Biologic Disease-Modifying Anti-Rheumatic Drugs (DMARDs).

The risk of cardiovascular (CV) disease is increased among patients with systemic autoimmune rheumatic diseases and remains an underserved area of medical need. Although traditional risk factors for CV disease, such as hypertension, smoking, dyslipidemia and obesity contribute to endothelial dysfunction in rheumatoid arthritis (RA), they are not enough on their own to explain the observed excess CV risk. Rather, systemic inflammation seems to play a pivotal role in both disease states. Considering the inflammatory process in autoimmune diseases, scientific interest has focused on recently introduced biologic disease-modifying agents (bDMARDS) such as inhibitors of Tumor Necrosis Factor- α (ΤΝF-α), Interleukins -1 (IL-1) and -6 (IL-6). Despite the widespread use of bDMARDS in RA and other chronic autoimmune inflammatory diseases, their precise impact on CV disease and outcome remains to be elucidated, while prospective randomized control trials assessing their impact on hard CV endpoints are scarce. In this review, we summarize current knowledge concerning the effect of bDMARDs on CV outcome and on the risk of developing CV disease in patients with systemic autoimmune rheumatic diseases.

Transfemoral transcatheter aortic valve replacement in the presence of a mitral prosthesis.

PURPOSE: In the current case series, we present our experience with the self-expanding CoreValve or Evolut R (Medtronic Inc.) in patients with severe symptomatic aortic valve stenosis and concomitant mitral valve prosthesis. METHODS: Twelve patients with previous mitral valve prosthesis underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and/or aortic valve regurgitation. All patients underwent evaluation with an echocardiogram, computed tomography and coronary angiogram. After the index intervention and before discharge all patients underwent transthoracic echocardiography. All outcomes were defined according to the Valve Academic Research Consortium-2 criteria. RESULTS: Eleven patients underwent transcatheter aortic valve replacement for severe symptomatic aortic valve stenosis and one patient for severe aortic valve regurgitation. There was immediate improvement of patients' hemodynamic status; no cases of procedural death, stroke, myocardial infarction, or urgent cardiac surgery occurred. There was no 30-day mortality and all patients improved, with 91.6% in functional New York Heart Association class I-II. CONCLUSION: The current study demonstrates that in patients with severe aortic valve stenosis or regurgitation and mitral valve prosthesis, the implantation of a self-expanding aortic valve via the transfemoral route is safe and feasible, with maintained long-term results.