Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. It has been proposed that noninvasive brain stimulation techniques may be used to understand the pathophysiology of FP and may represent a possible therapeutic option. In this paper, we reviewed transcranial magnetic stimulation studies on functional paralysis, focusing on their pathophysiological and therapeutical implications. Overall, there is general agreement on the integrity of corticospinal pathways in FP, while conflicting results have been found about the net excitability of the primary motor cortex and its excitatory/inhibitory circuitry in resting conditions. The possible involvement of spinal cord circuits remains an under-investigated area. Repetitive transcranial magnetic stimulation appears to have a potential role as a safe and viable option for the treatment of functional paralysis, but more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options

Curved Walking Rehabilitation with a Rotating Treadmill in Patients with Parkinson’s Disease: A Proof of Concept

Training subjects to step-in-place eyes open on a rotating platform while maintaining a fixed body orientation in space [podokinetic stimulation (PKS)] produces a posteffect consisting in inadvertent turning around while stepping-in-place eyes closed [podokinetic after-rotation (PKAR)]. Since the rationale for rehabilitation of curved walking in Parkinson's disease is not fully known, we tested the hypothesis that repeated PKS favors the production of curved walking in these patients, who are uneasy with turning, even when straight walking is little affected. Fifteen patients participated in 10 training sessions distributed in 3 weeks. Both counterclockwise and clockwise PKS were randomly administered in each session. PKS velocity and duration were gradually increased over sessions. The velocity and duration of the following PKAR were assessed. All patients showed PKAR, which increased progressively in peak velocity and duration. In addition, before and at the end of the treatment, all patients walked overground along linear and circular trajectories. Post-training, the velocity of walking bouts increased, more so for the circular than the linear trajectory. Cadence was not affected. This study has shown that parkinsonian patients learn to produce turning while stepping when faced with appropriate training and that this capacity translates into improved overground curved walking

Prediction of yields and composition of char from fast pyrolysis of commercial lignocellulosic materials, organosolv fractionated and torrefied olive stones

peer-reviewedThis study investigated the fast pyrolysis behaviour of torrefied olive stones, fractionated olive stones and lignocellulosic commercial compounds. Olive stones were reacted in a continuous industrial torrefaction unit. The olive stones were also fractionated into their main components in an organosolv reactor at temperatures from 170 to 190 ◦C in both the presence and absence of an acidic catalyst. All samples were reacted in a wire mesh reactor at different temperatures (800–1150 ◦C) and heating rates (400–1150 ◦C/s), and the solid product was characterised for its yield, morphology, and elemental composition. The char yields from fast pyrolysis of commercially available cellulose, hemicelluloses, and lignin were compared with yields of fractionated olive stones. A model was developed to compare the measured yields of olive stones with the predicted yields using fractionated or commercial components. The presence of acid during fractionation had a stronger effect than the temperature, particularly on the lignin fraction. The fractionated lignocellulosic compounds provided more accurate predictions of the char yields of olive stones, as compared to the commercial lignocellulosic compounds. The fractionation at 180 ◦C without acid catalyst gave the cellulose, hemicellulose, and lignin with highest degree of purity and resulted in the most accurate predictions of the experimental yields of olive stones. The results showed that interactions between the lignocellulosic components were not significant. The char yield of each fractioned compound and non-treated olive stones could be accurately predicted from the lignocellulosic content which has importance for biorefinery applications in which each fraction is used as a value-added product

Mitochondrial Role in Intrinsic Apoptosis Induced by a New Synthesized Chalcone in Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and the fourth cause of cancer-related deaths worldwide. Presently, a few drugs are available for HCC treatment and prevention, including both natural and synthetic compounds. In this study, a new chalcone, (E)-1-(2,4,6-triethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)prop-2-en-1-one (ETTC), was synthesized and its effects and mechanisms of action over human hepatoma cells were investigated. Cytotoxic activity was revealed in HCC cells, while no effects were observed in normal hepatocytes. In HCC cells, ETTC caused subG1 cell cycle arrest and apoptosis, characterized by nuclear fragmentation. The activation of caspases 3/7 and 9, the increase in pro-apoptotic BAX, and the decrease in anti-apoptotic BCL-2 suggest the activation of the intrinsic pathway of apoptosis. ETTC mitochondrial targeting is confirmed by the reduction in mitochondrial membrane potential and Complex I activity together with levels of superoxide anion increasing. Our outcomes prove the potential mitochondria-mediated antitumor effect of newly synthesized chalcone ETTC in HCC

Synthesis, characterization and cytotoxic activity on breast cancer cells of new half-titanocene derivatives

A series of novel titanocene-complexes has been prepared and evaluated for their growth regulatory effects in MCF7 and SkBr3 breast cancer cells. The capability of some of these compound to elicit relevant repressive effects on cancer cell growth could be taken into account towards novel pharmacological approaches in cancer therapy

Cardiovascular involvement after liver transplantation: role of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis

Patients submitted to liver transplantation (LT) are exposed to high risk of cardiovascular (CV) complications which are the main determinants of both short-term and long-term morbidity and mortality in LT. Non-alcoholic fatty liver disease (NAFLD) is a very frequent condition in general population and is associated with a high risk of cardiovascular disease (CVD) which represents the first cause of death of these patients. NAFLD is predicted to become the first indication to LT and nowadays is also frequently detected in patients submitted to LT for other indications. Thus, the risk of CVD in patients submitted to LT is forecasted to increase in the next years. In this review the extent of CV involvement in patients submitted to LT and the role of NAFLD, either recurring after transplantation or as de novo presentation, in increasing CV risk is analysed. The risk of developing metabolic alterations, including diabetes, hypertension, dyslipidemia and weight gain, all manifestations of metabolic syndrome, occurring in the first months after LT, is depicted. The different presentations of cardiac involvement, represented by early atherosclerosis, coronary artery disease, heart failure and arrhythmias in patients with NAFLD submitted to LT is described. In addition, the tools to detect cardiac alterations either before or after LT is reported providing the possibility for an early diagnosis of CVD and an early therapy able to reduce morbidity and mortality for these diseases. The need for long-term concerted multidisciplinary activity with dietary counseling and exercise combined with drug treatment of all manifestations of metabolic syndrome is emphasized

Combined analytical strategies for chemical and physical characterization of tar from torrefaction of olive stone

The advance in analytical methodology is critical for progress in 1) biorefinery and 2) torrefaction product commercialization. The chemical characterisation of torrefaction liquid and concentrated tar produced by Arigna Fuels’ pyrolysis plant allowed identification of polar, volatile, non-volatile compounds, species containing organically bound sulphur and nitrogen heteroatoms. The results suggest that only combined use of ion chromatography with Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, and 1H-13C HS-QC can provide comprehensive information on sugar-like material and lignin-derived compounds. Due to the technical robustness and short analysis time, Fourier Transform Ion Cyclotron Resonance Mass Spectrometer was found to be a promising tool for tar analysis containing heavy molecular compounds. Importantly from a technological standpoint, the presence of aromatic and saturated compounds in both liquid and concentrated tar samples indicated the predominance of lignin-derived compounds over products originating from cellulose and hemicellulose polymers.publishedVersio

Investigation of the Complexes Formed between PARP1 Inhibitors and PARP1 G-Quadruplex at the Gene Promoter Region

DNA repair inhibitors are one of the latest additions to cancer chemotherapy. In general, chemotherapy produces DNA damage but tumoral cells may become resistant if enzymes involved in DNA repair are overexpressed and are able to reverse DNA damage. One of the most successful drugs based on modulating DNA repair are the poly(ADP-ribose) polymerase 1 (PARP1) inhibitors. Several PARP1 inhibitors have been recently developed and approved for clinical treatments. We envisaged that PARP inhibition could be potentiated by simultaneously modulating the expression of PARP 1 and the enzyme activity, by a two-pronged strategy. A noncanonical G-quadruplex-forming sequence within the PARP1 promoter has been recently identified. In this study, we explored the potential binding of clinically approved PARP1 inhibitors to the G-quadruplex structure found at the gene promoter region. The results obtained by NMR, CD, and fluorescence titration confirmed by molecular modeling demonstrated that two out the four PARP1 inhibitors studied are capable of forming defined complexes with the PARP1 G-quadruplex. These results open the possibility of exploring the development of better G-quadruplex binders that, in turn, may also inhibit the enzyme