Antisenescence effect of REAC biomodulation to counteract the evolution of myelodysplastic syndrome.

About 30 percent of patients diagnosed with myelodysplastic syndromes (MDS) progress to acute myeloid leukemia (AML). The senescence of bone marrow?derived mesenchymal stem cells (BMSCs) seems to be one of the determining factors in inducing this drift. Research is continuously looking for new methodologies and technologies that can use bioelectric signals to act on senescence and cell differentiation towards the phenotype of interest. The Radio Electric Asymmetric Conveyer (REAC) technology, aimed at reorganizing the endogenous bioelectric activity, has already shown to be able to determine direct cell reprogramming effects and counteract the senescence mechanisms in stem cells. Aim of the present study was to prove if the anti-senescence results previously obtained in different kind of stem cells with the REAC Tissue optimization - regenerative (TO-RGN) treatment, could also be observed in BMSCs, evaluating cell viability, telomerase activity, p19ARF, P21, P53, and hTERT gene expression. The results show that the REAC TO-RGN treatment may be a useful tool to counteract the BMSCs senescence which can be the basis of AML drift. Nevertheless, further clinical studies on humans are needed to confirm this hypothesis.

Central odontogenic fibroma interesting the maxillary sinus. A case report and literature survey.

Odontogenic fibroma (OF) is a rare benign odontogenic tumor deriving from the dental mesenchymal tissue and accounting for less than 5% of all odontogenic tumors. This paper presents an aggressive histologically diagnosed central odontogenic fibroma (COF) in a 17-year-old girl characterized by asymptomatic rapid growth with massive replenishment of the left maxillary sinus. We carried out a review of the literature to retrieve all published cases of COF especially focused on radiographic aspects and surgical treatment of cases characterized by clinical aggressive behaviour, as we observed in our patient. Search strategy included retrieval of English language papers, published from 1966 to today, in dental journals on MEDLINE/PubMed and EMBASE, and hand-searching of the bibliography of retrieved papers. Sixty-nine cases of COF were identified from 1954 to 2003 and a new one was added. We have compared characteristics of COFs according to age, gender, location, clinical and radiographic findings of aggressive development, and histology. We discuss clinical and radiographic aspects of our case compared with COFs previously published. We give suggestions for surgical treatment of COF in case of aggression to important anatomical structures.

Stem cell senescence. Effects of REAC technology on telomerase-independent and telomerase-dependent pathways.

Decline in the gene expression of senescence repressor Bmi1, and telomerase, together with telomere shortening, underlay senescence of stem cells cultured for multiple passages. Here, we investigated whether the impairment of senescence preventing mechanisms can be efficiently counteracted by exposure of human adipose-derived stem cells to radio electric asymmetrically conveyed fields by an innovative technology, named Radio Electric Asymmetric Conveyer (REAC). Due to REAC exposure, the number of stem cells positively stained for senescence associated ß-galactosidase was significantly reduced along multiple culturing passages. After a 90-day culture, REAC-treated cells exhibited significantly higher transcription of Bmi1 and enhanced expression of other stem cell pluripotency genes and related proteins, compared to unexposed cells. Transcription of the catalytic telomerase subunit (TERT) was also increased in REAC-treated cells at all passages. Moreover, while telomere shortening occurred at early passages in both REAC-treated and untreated cells, a significant rescue of telomere length could be observed at late passages only in REAC-exposed cells. Thus, REAC-asymmetrically conveyed radio electric fields acted on a gene and protein expression program of both telomerase-independent and telomerase-dependent patterning to optimize stem cell ability to cope with senescence progression.

Modeling the motor striatum under Deep Brain Stimulation in normal and MPTP conditions.

Striatum (STR) is the major input stage of the basal ganglia (BG). It combines information from cortex, subthalamic nucleus (STN) and external globus pallidus (GPe), and projects to the output stages of the BG, where selection between concurrent motor programs is performed. Parkinson's disease (PD) reduces the concentration of dopamine (DA, a neurotransmitter) in STR and changes in the level of DA correlate with the onset of PD motor disorders. Though STR plays a pivotal role in BG, its behavior under PD and Deep Brain Stimulation (DBS) is still unclear. We develop point-process models of the STR neurons as a function of the activity in GPe, cortex, and DBS. We use single unit recordings from a monkey under STN DBS at different frequencies before and after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridine (MPTP) to develop PD motor symptoms. The models suggest that STR neurons have prominent bursting activity in normal conditions, positive correlation with cortex (3-10 ms delay), and mild negative correlation with GPe (1-5 ms lag). DA depletion evokes 30-60 Hz oscillations, and increases the propensity of each neuron to be inhibited by surrounding neurons. DBS elicits antidromical activation, masks existent dynamics, reinforces dependencies between nuclei, and entrains at the stimulation frequency in both conditions.

Modeling the effects of Deep Brain Stimulation on sensorimotor cortex in normal and MPTP conditions.

Deep Brain Stimulation (DBS) is an effective surgical therapy for the treatment of movement disorders in Parkinson's disease (PD) and other neurological pathologies. DBS is known to modulate the spiking activity of the neurons within the basal ganglia, but how such modulation impacts the primary sensorimotor cortex is still uncertain. In this study a monkey was stimulated with DBS at several frequencies in the subthalamic nucleus (STN) before and after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to develop PD symptoms, while single unit recordings are simultaneously obtained from the sensorimotor cortex. We exploit such data to develop point-process input-output models of the cortical neurons. Our models describe the effects of stimulation in normal and MPTP conditions and investigate the influence of the stimulation frequency on the neuronal activity. Our models show increased synchronization of the cortical neurons in MPTP vs. normal conditions before stimulation, suggest that STN DBS impacts the cortical activity by antidromically eliciting spikes at the stimulation frequency, and support the hypothesis that high frequency DBS partially masks the effects of thalamo-cortical input.