Free Mg(2+ )concentration in the calf muscle of glycogen phosphorylase and phosphofructokinase deficiency patients assessed in different metabolic conditions by (31)P MRS

BACKGROUND: The increase in cytosolic free Mg(2+ )occurring during exercise and initial recovery in human skeletal muscle is matched by a decrease in cytosolic pH as shown by in vivo phosphorus magnetic resonance spectroscopy ((31)P MRS). To investigate in vivo to what extent the homeostasis of intracellular free Mg(2+ )is linked to pH in human skeletal muscle, we studied patients with metabolic myopathies due to different disorders of glycogen metabolism that share a lack of intracellular acidification during muscle exercise. METHODS: We assessed by (31)P MRS the cytosolic pH and free magnesium concentration ([Mg(2+)]) in calf muscle during exercise and post-exercise recovery in two patients with McArdle's disease with muscle glycogen phosphorylase deficiency (McArdle), and two brothers both affected by Tarui's disease with muscle phosphofructokinase deficiency (PFK). RESULTS: All patients displayed a lack of intracellular acidosis during muscle exercise. At rest only one PFK patient showed a [Mg(2+)] higher than the value found in control subjects. During exercise and recovery the McArdle patients did not show any significant change in free [Mg(2+)], while both PFK patients showed decreased free [Mg(2+)] and a remarkable accumulation of phosphomonoesters (PME). During initial recovery both McArdle patients showed a small increase in free [Mg(2+)] while in PFK patients the pattern of free [Mg(2+)] was related to the rate of PME recovery. CONCLUSION: i) homeostasis of free [Mg(2+)] in human skeletal muscle is strongly linked to pH as shown by patients' [Mg(2+)] pattern during exercise; ii) the pattern of [Mg(2+)] during exercise and post-exercise recovery in both PFK patients suggests that [Mg(2+)] is influenced by the accumulation of the phosphorylated monosaccharide intermediates of glycogenolysis, as shown by the increased PME peak signal. iii) (31)P MRS is a suitable tool for the in vivo assessment of free cytosolic [Mg(2+)] in human skeletal muscle in different metabolic conditions

The Biochemical and Cellular Basis for Nutraceutical Strategies to Attenuate Neurodegeneration in Parkinson’s Disease

Future therapeutic intervention that could effectively decelerate the rate of degeneration within the substantia nigra pars compacta (SNc) could add years of mobility and reduce morbidity associated with Parkinson’s disease (PD). Neurodegenerative decline associated with PD is distinguished by extensive damage to SNc dopaminergic (DAergic) neurons and decay of the striatal tract. While genetic mutations or environmental toxins can precipitate pathology, progressive degenerative succession involves a gradual decline in DA neurotransmission/synaptic uptake, impaired oxidative glucose consumption, a rise in striatal lactate and chronic inflammation. Nutraceuticals play a fundamental role in energy metabolism and signaling transduction pathways that control neurotransmission and inflammation. However, the use of nutritional supplements to slow the progression of PD has met with considerable challenge and has thus far proven unsuccessful. This review re-examines precipitating factors and insults involved in PD and how nutraceuticals can affect each of these biological targets. Discussed are disease dynamics (Sections 1 and 2) and natural substances, vitamins and minerals that could impact disease processes (Section 3). Topics include nutritional influences on α-synuclein aggregation, ubiquitin proteasome function, mTOR signaling/lysosomal-autophagy, energy failure, faulty catecholamine trafficking, DA oxidation, synthesis of toxic DA-quinones, o-semiquinones, benzothiazolines, hyperhomocyseinemia, methylation, inflammation and irreversible oxidation of neuromelanin. In summary, it is clear that future research will be required to consider the multi-faceted nature of this disease and re-examine how and why the use of nutritional multi-vitamin-mineral and plant-based combinations could be used to slow the progression of PD, if possible

In vivo evidence of neuronal loss in the hypothalamus of narcoleptic patients

none7nononeR. Lodi; C. Tonon; L. Vignatelli; S. Iotti; P. Montagna; G. Plazzi; B. BarbiroliR. Lodi; C. Tonon; L. Vignatelli; S. Iotti; P. Montagna; G. Plazzi; B. Barbirol

An UAV-Based Experimental Setup for Propagation Characterization in Urban Environment

A measurement setup, including millimeter-wave and ultrawideband transceivers mounted on both a customized unmanned aerial vehicle and a ground station and a measurement procedure for full 3-D wireless propagation analysis, is described in this work. The custom-made developed system represents a flexible solution for the characterization of wireless channels and especially of urban propagation, as the drone might be easily located almost anywhere from ground level to the buildings’ rooftop and beyond. The double-directional properties of the channel can be achieved by rotating directive antennas at the link ends. Other possible applications in urban contexts include the study of outdoor-to-indoor penetration, line-of-sight to non-line-of-sight transition, 3-D scattering from buildings, and air-to-ground channel characterization for drone-assisted wireless communications