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Objective Sub-motor threshold 5 Hz repetitive paired associative stimulation (5 Hz-rPAS25ms) produces a long-lasting increase in corticospinal excitability. Assuming a spike-timing dependent plasticity-like (STDP-like) mechanism, we hypothesized that 5 Hz-rPAS at a shorter inter-stimulus interval (ISI) of 15 ms (5 Hz-rPAS15ms) would exert a lasting inhibitory effect on corticospinal excitability. Methods 20 healthy volunteers received two minutes of 5 Hz-rPAS15ms. Transcranial magnetic stimulation (TMS) was applied over the motor hotspot of the right abductor pollicis brevis muscle at 90% active motor threshold. Sub-motor threshold peripheral electrical stimulation was given to the left median nerve 15 ms before each TMS pulse. We assessed changes in mean amplitude of the unconditioned motor evoked potential (MEP), short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition (LAI), and cortical silent period (CSP) before and for 60 minutes after 5-Hz rPAS15ms. Results Subthreshold 5-Hz rPAS15ms produced a 20–40% decrease in mean MEP amplitude along with an attenuation in SAI, lasting at least 60 minutes. A follow-up experiment revealed that MEP facilitation was spatially restricted to the target muscle. Conclusions Subthreshold 5-Hz rPAS15ms effectively suppresses corticospinal excitability. Together with the facilitatory effects of subthreshold 5-Hz rPAS25ms (Quartarone et al., J Physiol 2006;575:657–670), the results show that sub-motor threshold 5-Hz rPAS induces STDP-like bidirectional plasticity in the motor cortex. Significance The results of the present study provide a new short-time paradigm of long term depression (LTD) induction in human sensory-motor cortex.

Background. Surround inhibition is a system that sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, this mechanism probably contributes to the selection of voluntary movements, and it seems to be lost in dystonia. Objectives. To explore if sensory information is abnormally processed and integrated in focal hand dystonia (FHD) and if surround inhibition phenomena are operating during sensory-motor plasticity and somatosensory integration in normal humans and in patients with FHD. Methods. We looked at the MEP facilitation obtained after 5 Hz repetitive paired associative stimulation of median (PAS M), ulnar (PAS U), and median + ulnar nerve (PAS MU) stimulation in 8 normal subjects and 8 FHD. We evaluated the ratio MU/(M + U) ∗ 100 and the spatial and temporal somatosensory integration recording the somatosensory evoked potentials (SEPs) evoked by a dual nerve input. Results. FHD had two main abnormalities: first, the amount of facilitation was larger than normal subjects; second, the spatial specificity was lost. The MU/(M + U) ∗ 100 ratio was similar in healthy subjects and in FHD patients, and the somatosensory integration was normal in this subset of patients. Conclusions. The inhibitory integration of somatosensory inputs and the somatosensory inhibition are normal in patients with focal dystonia as well as lateral surrounding inhibition phenomena during sensory-motor plasticity in FHD.

The use of the products derived from the olive tree on human health dates back centuries. In several civilizations, the olive tree had and still has a very strong cultural and religious symbolism. Notably, the official seal and emblem of the World Health Organization features the rod of Asclepius over a world map surrounded by olive tree branches, chosen as a symbol of peace and health. Recently, accumulating experimental, clinical and epidemiological data have provided support to the traditional beliefs of the beneficial effect provided by olive derivates. In particular, the polyphenols present in olive leaves, olives, virgin (unrefined) olive oil and olive mill waste are potent antioxidant and radical scavengers with anti-tumor and anti-inflammatory properties. Here, we review the positive impact on human health of oleuropein, the most prevalent polyphenol present in olives. In addition, we provide data collected in our laboratory on the role of oleuropein in counteracting lipid accumulation in a mouse model of non-alcoholic fatty liver disease.

Background Certolizumab Pegol (CZP), administered every 2 weeks in combination with Methotrexate (MTX), showed rapid efficacy and had an acceptable safety profile in patients(pts) with RA in several clinical trials. Objectives To confirm the efficacy and safety of CZP+MTX in pts with active RA and an previous inadequate response to MTX. Methods In this study 17 pts [mean age±DS:50±7.1 years (min-max 38-62)] with active RA [CRP: 11.1±5.7 mg/L (6.3-24), ESR: 38.9±12.6 (24-67) mm/h, DAS28(ESR): 4.7±0.4 (4.1-5.2), HAQ: 1.9±0.3 (1,0-2.3)] received CZP every two weeks (Wks) [a dose of 400mg for the first three times (at Wks 0, 2 and 4) followed by 200mg] and a stable dose of MTX (10-20 mg/Wk) for 52 weeks. Results 16 pts completed the study, because a case of pancytopenia determined the discontinuation of the drug in one pt. This was the only adverse event. DAS28(ESR) was significantly lower after 52 Wks (P=0.00013). HAQ, pain and global disease activity had significantly improved after 52 Wks. In table I is shown the average value of DAS28(ESR), ESR, CRP and HAQ at the beginning of the study (T0) and after 52 Weeks (T52). Image/graph Conclusions Use of CZP 200mg (after three initial subministrations of 400 mg) every 2 Wks + MTX resulted in a rapid and sustained reduction of RA signs, symptoms and pain, and improved physical function. CZP had an acceptable safety profile. This confirms the efficacy and safety of CZP in MTX refractary RA. Disclosure of Interest None Declared