Essential tremor amplitude modulation by median nerve stimulation.

Essential tremor is a common neurological disorder, characterised by involuntary shaking of a limb. Patients are usually treated using medications which have limited effects on tremor and may cause side-effects. Surgical therapies are effective in reducing essential tremor, however, the invasive nature of these therapies together with the high cost, greatly limit the number of patients benefiting from them. Non-invasive therapies have gained increasing traction to meet this clinical need. Here, we test a non-invasive and closed-loop electrical stimulation paradigm which tracks peripheral tremor and targets thalamic afferents to modulate the central oscillators underlying tremor. To this end, 9 patients had electrical stimulation delivered to the median nerve locked to different phases of tremor. Peripheral stimulation induced a subtle but significant modulation in five out of nine patients-this modulation consisted mainly of amplification rather than suppression of tremor amplitude. Modulatory effects of stimulation were more pronounced when patient's tremor was spontaneously weaker at stimulation onset, when significant modulation became more frequent amongst subjects. This data suggests that for selected individuals, a more sophisticated control policy entailing an online estimate of both tremor phase and amplitude, should be considered in further explorations of the treatment potential of tremor phase-locked peripheral stimulation.

Thalamocortical dynamics underlying spontaneous transitions in beta power in Parkinsonism.

Parkinson's disease (PD) is a neurodegenerative condition in which aberrant oscillatory synchronization of neuronal activity at beta frequencies (15-35 Hz) across the cortico-basal ganglia-thalamocortical circuit is associated with debilitating motor symptoms, such as bradykinesia and rigidity. Mounting evidence suggests that the magnitude of beta synchrony in the parkinsonian state fluctuates over time, but the mechanisms by which thalamocortical circuitry regulates the dynamic properties of cortical beta in PD are poorly understood. Using the recently developed generic Dynamic Causal Modelling (DCM) framework, we recursively optimized a set of plausible models of the thalamocortical circuit (n = 144) to infer the neural mechanisms that best explain the transitions between low and high beta power states observed in recordings of field potentials made in the motor cortex of anesthetized Parkinsonian rats. Bayesian model comparison suggests that upregulation of cortical rhythmic activity in the beta-frequency band results from changes in the coupling strength both between and within the thalamus and motor cortex. Specifically, our model indicates that high levels of cortical beta synchrony are mainly achieved by a delayed (extrinsic) input from thalamic relay cells to deep pyramidal cells and a fast (intrinsic) input from middle pyramidal cells to superficial pyramidal cells. From a clinical perspective, our study provides insights into potential therapeutic strategies that could be utilized to modulate the network mechanisms responsible for the enhancement of cortical beta in PD. Specifically, we speculate that cortical stimulation aimed to reduce the enhanced excitatory inputs to either the superficial or deep pyramidal cells could be a potential non-invasive therapeutic strategy for PD.

Electrochemical behavior and determination of major phenolic antioxidants in selected coffee samples.

The redox behavior of commercial roasted coffee products were evaluated by electroanalysis, whereas high performance liquid chromatography (HPLC) was used for determination of cinnamic acid markers, the total phenolic content (TPC) was achieved by Folin-Ciocalteu assay, and the traditional DPPH (1-diphenyl-2-picrylhydrazyl) method for antioxidant power determination. In turn, an optimized electrochemical index was proposed to estimate the antioxidant power of different samples and it was found a great correlation between all methods. The voltammetric profile of all coffee samples was quite similar, presenting the same number of peaks at the same potential values. Minor differences on current levels were in agreement with the total phenolic and major markers content, as well as, to the antioxidant power. Therefore, the electrochemical methods showed to be practical, low cost and very useful to evaluate the antioxidant properties of coffee samples, which is a relevant quality parameter of this widely consumed beverage.

Blocking the L-type Ca2+ channel (Cav 1.2) is the key mechanism for the vascular relaxing effect of Pterodon spp. and its isolated diterpene methyl-6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate.

Pterodon spp. Vogel (Fabaceae), popularly known as "sucupira", has ethnopharmacological application which is described as having antispasmodic and relaxant effects. Hence, it was hypothesized that sucupira oil-resin (SOR) could induce smooth muscle relaxation. So, this study investigated the mechanisms involved in the vasorelaxant effect of SOR and its isolated diterpene (methyl-6α-acetoxy-7ß-hydroxyvouacapan-17ß-oate). Vascular reactivity experiments were performed using rat aortic rings (n=5-8) with (E+) or without endothelium (E-) in an isolated bath organ. The SOR (0-56 µg/mL) relaxed phenylephrine (E+: 86.7±7.1%; E-: 92.3±4.7%) and KCl contracted rings (E-: 97.1±2.8%). In the same way, diterpene (0-48 µg/mL) also relaxed phenylephrine (E+: 94.5±3.6%; E-: 92.2±3.4%) and KCl contracted rings (E-: 99.7±0.2%). The pre-incubation of arterial rings with cyclopiazonic acid (reticular Ca2+-ATPase inhibitor), tetraethylammonium (K+ channels blocker) or MDL-12,330A (adenylyl cyclesinhibitor) did not modify either SOR- or diterpeneinduced vasorelaxation. However, ODQ (guanylyl cyclase inhibitor) impaired only diterpene-induced vasorelaxation. SOR and diterpene significantly reduced CaCl2-induced contraction stimulated by Bay K8644 (1 µM), phenylephrine (0.1 µM) or KCl solution (40 mM). Computational molecular docking studies demonstrated that the vasodilator effect of diterpene relies on blocking the Cav 1.2 channel, and patch clamp results showed that diterpene substantially decreased the ionic current through Cav 1.2 in freshly dissociated vascular smooth muscle cells. These findings suggest that SOR and its isolated diterpene induce endothelium-independent vascular relaxation by blocking the L-type Ca2+ channel (Cav 1.2).

Vasorelaxant and Hypotensive Effects of Jaboticaba Fruit (Myrciaria cauliflora) Extract in Rats.

This study's aim was to determine the effect of hydroalcoholic extract of M. cauliflora (HEMC) on vascular tension and blood pressure in rats. In our in vitro studies using precontracted isolated aortas from rats, HEMC and acetylcholine (positive control) induced relaxation only in vessels with endothelium. Pretreatment with L-NAME (NO synthase inhibitor) or ODQ (soluble guanylyl cyclase (sGC) inhibitor) abolished the HEMC-induced relaxation. The treatment with MDL-12,330A (adenylyl cyclase (AC) inhibitor) or diclofenac (COX inhibitor) reduced HEMC-induced vasorelaxation. The blockade of muscarinic and ß-adrenergic receptors (by atropine and propranolol, resp.) did not promote changes in HEMC-induced vasorelaxation. In our in vivo studies, catheters were inserted into the right femoral vein and artery of anesthetized rats for HEMC infusion and the measurement of blood pressure, heart rate, and aortic blood flow. The intravenous infusion of HEMC produced hypotension and increased aortic blood flow with no changes in heart rate. These findings showed that HEMC induces endothelium-dependent vascular relaxation and hypotension with no alteration in heart rate. The NO/sGC/cGMP pathway seems to be the main cellular route involved in the vascular responsiveness.

Diuretic effects and urinary electrolyte excretion induced by Aspidosperma subincanum Mart. and the involvement of prostaglandins in such effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Aspidosperma subincanum Mart. is a medicinal herb known for its diuretic properties and used for the treatment of cardiovascular-related illnesses. Although our earlier study has shown that the ethanol extract of Aspidosperma subincanum (EEAS) induces hypotension and vasodilation, no scientific data have been recorded to evaluate the diuretic effects of this Brazilian medicinal plant. The aim of this study was to evaluate the diuretic activity of EEAS, and possible mechanism of action, using Wistar rats. MATERIAL AND METHODS: EEAS (60 and 120mg/kg), furosemide (20mg/kg) or saline (control) were orally administered to rats individually held in metabolic cages for urine collection 1, 2, 4, 6, 8, 12 and 24h after treatment. In order to evaluate the involvement of prostaglandins in the diuretic action of EEAS, the animals received piroxicam (5mg/kgi.p.), a nonselective inhibitor of cyclooxygenase, before treatment with EEAS at 120mg/kg. The control groups received only saline (NaCl, 0.9%), or saline and piroxicam. Urinary volume, electrolyte excretion and pH were measured. RESULTS: Oral administration of EEAS 60 and 120mg/kg significantly increased diuresis and electrolyte excretion of Na(+) and K(+) on a continuous basis throughout the study period. Both EEAS 60 and 120mg/kg caused a relative increase of around 77% and 142%, respectively, in cumulative diuresis compared with the control group. From 4th hour until the end of the experiment, the group treated with EEAS 120mg/kg provided a greater excretion of Na(+) than the furosemide group. The diuretic effects of EEAS were neutralized by piroxicam between 4 and 8h after treatment. CONCLUSION: The results suggest that EEAS could present compound(s) responsible for diuretic activities, and the mechanism could involve the prostaglandin system.