Transcranial sonography in the diagnosis, follow-up and treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

We used a modified transcranial sonography technique to study the cortex of the temporal lobe, a brain region involved in the processing of functions that are often compromised in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) patients. We studied the meninges, the subarachnoidal space and the cortex. The spatial resolution and the ability to visualize structures of 200-300 µm size, led us to hypothesize that the linear structures parallel to the subarachnoidal space could be referred to the neuronal layers of the cortex. In real-time mode, we could observe pulsation of the meninges and the cortex synchronous with the heart beat and independent of blood flow. This pulsation was more evident at the level of the meninges, but it was also appreciable at the level of the layers of the cortex and it was not accompanied by any type of flow. In addition to these findings, we observed that the subject undergoing the procedure experienced a series of changes that might prove potentially useful in the treatment of ME/CFS. In particular, we observed a decrease of tachycardia accompanied by an increase in systolic blood pressure and by a significant increase in muscle strength measured by the degree of muscle fibre shortening at the level of the biceps brachii. These findings, together with the low cost and simplicity of the procedure, suggest that modified transcranial sonography has a significant potential in the study and treatment of ME/CFS

ACE/VDR gene polymorphisms and bioelectrical impedance analysis in predicting athletic performances of Italian Young soccer players.

We evaluated the association between 2 genetic polymorphisms known to be involved in fitness and performance, and anthropometric features, body composition, and athletic performances in young male soccer players with the goal of identifying genetic profiles that can be used to achieve maximal results from training. One hundred twenty-five medium-high-level male soccer players were genotyped for angiotensin-converting enzyme (ACE) I/D, and vitamin D receptor (VDR) FokI gene polymorphisms and scored for anthropometric measurements, body composition, and athletic performance. Body mass index, fat mass, fat-free mass, resistance, reactance, impedance, phase angle (PA), and body cell mass were measured. Athletic performance was evaluated by squat jump, countermovement jump (CMJ), 2-kg medicine ball throw, 10- and 20-m sprint time. We observed that the homozygous ff genotype of the VDR gene was significantly more represented in young soccer players than in a matched sedentary population. Values of reactance and PA were differently distributed in ACE and VDR genotypes with high mean values in subjects with DD (ACE) and FF (VDR) genotypes. No correlation was observed between ACE or VDR genotypes and 2-kg medicine ball throw, 10- and 20-m sprint times. The ID genotype of ACE was associated with the best performances in squat jump and CMJ. Our results suggest that determination of ACE and VDR genotypes might help select those young athletes harboring the most favorable genetic potential to succeed in soccer

Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

According to the World Health Organization, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neurological disease characterized by widespread inflammation and multi-systemic neuropathology. Aetiology and pathogenesis are unknown, and several agents have been proposed as causative agents or as factors perpetuating the syndrome. Exposure to heavy metals, with particular reference to mercury and gold in dental amalgams, has been considered among the triggers of ME/CFS. Here we hypothesize that cadmium, a widespread occupational and environmental heavy metal pollutant, might be associated with some of the neurological findings described in ME/CFS. In fact, ME/CFS patients show a decrease of the volume of the gray matter in turn associated with objective reduction of physical activity. Cadmium induces neuronal death in cortical neurons through a combined mechanism of apoptosis and necrosis and it could then be hypothesized that cadmium-induced neuronal cell death is responsible for some of the effects of cadmium on the central nervous system, i.e. a decrease in attention level and memory in exposed humans as well as to a diminished ability for training and learning in rats, that are symptoms typical of ME/CFS. This hypothesis can be tested by measuring cadmium exposure in a cohort of ME/CFS patients compared with matched healthy controls, and by measuring gray matter volume in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients. In addition, we hypothesize that cadmium exposure could be associated with reduced cerebral blood flow in ME/CFS patients because of the disruptive effects of cadmium on angiogenesis. In fact, cadmium inhibits angiogenesis and low global cerebral flow is associated with abnormal brain neuroimaging results and brain dysfunction in the form of reduced cognitive testing scores in ME/CFS patients. This hypothesis can be tested by measuring cerebral cortex blood flow in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients. If our hypothesis is demonstrated correct, the consequences could affect prevention, early diagnosis, and treatment of ME/CFS. Implications in early diagnosis could entail the evaluation of symptoms typical of ME/CFS in cadmium-exposed subjects as well as the search for signs of exposure to cadmium in subjects diagnosed with ME/CFS. Nutritional supplementation of magnesium and zinc could then be considered, since these elements have been proposed in the prophylaxis and therapy of cadmium exposure, and magnesium was demonstrated effective on ME/CFS patients' symptom profiles

Alcohol-induced blood-brain barrier impairment: An in vitro study

In recent years, alcohol abuse has dramatically grown with deleterious consequence for people’s health and, in turn, for health care costs. It has been demonstrated, in humans and animals, that alcohol intoxication induces neuroinflammation and neurodegeneration thus leading to brain impairments. Furthermore, it has been shown that alcohol consumption is able to impair the blood– brain barrier (BBB), but the molecular mechanisms underlining this detrimental effect have not been fully elucidated. For this reason, in this study we investigated the effects of alcohol exposure on a rat brain endothelial (RBE4) cell line, as an in vitro-validated model of brain microvascular endothelial cells. To assess whether alcohol caused a concentration-related response, the cells were treated at different times with increasing concentrations (10–1713 mM) of ethyl alcohol (EtOH). Microscopic and molecular techniques, such as cell viability assay, immunofluorescence and Western blotting, were used to examine the mechanisms involved in alcohol-induced brain endothelial cell alterations including tight junction distribution, apoptosis, and reactive oxygen species production. Our findings clearly demonstrate that alcohol causes the formation of gaps between cells by tight junction disassembly, triggered by the endoplasmic reticulum and oxidative stress, highlighted by GRP78 chaperone upregulation and increase in reactive oxygen species production, respectively. The results from this study shed light on the mechanisms underlying alcohol-induced blood–brain barrier dysfunction and a better understanding of these processes will allow us to take advantage of developing new therapeutic strategies in order to prevent the deleterious effects of alcohol

Cannabidiol protects dopaminergic neuronal cells from cadmium

The protective effect of cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, against neuronal toxicity induced by cadmium chloride (CdCl2 10 μM) was investigated in a retinoic acid (RA)-differentiated SH-SY5Y neuroblastoma cell line. CBD (1 μM) was applied 24 h before and removed during cadmium (Cd) treatment. In differentiated neuronal cells, CBD significantly reduced the Cd-dependent decrease of cell viability, and the rapid reactive oxygen species (ROS) increase. CBD significantly prevented the endoplasmic reticulum (ER) stress (GRP78 increase) and the subcellular distribution of the cytochrome C, as well as the overexpression of the pro-apoptotic protein BAX. Immunocytochemical analysis as well as quantitative protein evaluation by western blotting revealed that CBD partially counteracted the depletion of the growth associated protein 43 (GAP43) and of the neuronal specific class III β-tubulin (β3 tubulin) induced by Cd treatment. These data showed that Cd-induced neuronal injury was ameliorated by CBD treatment and it was concluded that CBD may represent a potential option to protect neuronal cells from the detrimental effects of Cd toxicity

A novel role for a major component of the vitamin D axis: vitamin D binding protein-derived macrophage activating factor induces human breast cancer cell apoptosis through stimulation of macrophages.

The role of vitamin D in maintaining health appears greater than originally thought, and the concept of the vitamin D axis underlines the complexity of the biological events controlled by biologically active vitamin D (1,25(OH)(2)D3), its two binding proteins that are the vitamin D receptor (VDR) and the vitamin D-binding protein-derived macrophage activating factor (GcMAF). In this study we demonstrate that GcMAF stimulates macrophages, which in turn attack human breast cancer cells, induce their apoptosis and eventually phagocytize them. These results are consistent with the observation that macrophages infiltrated implanted tumors in mice after GcMAF injections. In addition, we hypothesize that the last 23 hydrophobic amino acids of VDR, located at the inner part of the plasma membrane, interact with the first 23 hydrophobic amino acids of the GcMAF located at the external part of the plasma membrane. This al1ows 1,25(OH)(2)D3 and oleic acid to become sandwiched between the two vitamin D-binding proteins, thus postulating a novel molecular mode of interaction between GcMAF and VDR. Taken together, these results support and reinforce the hypothesis that GcMAF has multiple biological activities that could be responsible for its anti-cancer effects, possibly through molecular interaction with the VDR that in turn is responsible for a multitude of non-genomic as well as genomic effects