Cannabinoids in the treatment of epilepsy: current status and future prospects

Cannabidiol (CBD) is one of the prominent phytocannabinoids found in Cannabis sativa, differentiating from Δ9-tetrahydrocannabinol (THC) for its non-intoxicating profile and its antianxiety/antipsychotic effects. CBD is a multi-target drug whose anti-convulsant properties are supposed to be independent of endocannabinoid receptor CB1 and might be related to several underlying mechanisms, such as antagonism on the orphan GPR55 receptor, regulation of adenosine tone, activation of 5HT1A receptors and modulation of calcium intracellular levels. CBD is a lipophilic compound with low oral bioavailability (6%) due to poor intestinal absorption and high first-pass metabolism. Its exposure parameters are greatly influenced by feeding status (ie, high fatcontaining meals). It is mainly metabolized by cytochrome P 450 (CYP) 3A4 and 2C19, which it strongly inhibits. A proprietary formulation of highly purified, plant-derived CBD has been recently licensed as an adjunctive treatment for Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), while it is being currently investigated in tuberous sclerosis complex. The regulatory agencies’ approval was granted based on four pivotal double-blind, placebocontrolled, randomized clinical trials (RCTs) on overall 154 DS patients and 396 LGS ones, receiving CBD 10 or 20 mg/kg/day BID as active treatment. The primary endpoint (reduction in monthly seizure frequency) was met by both CBD doses. Most patients reported adverse events (AEs), generally from mild to moderate and transient, which mainly consisted of somnolence, sedation, decreased appetite, diarrhea and elevation in aminotransferase levels, the last being documented only in subjects on concomitant valproate therapy. The interaction between CBD and clobazam, likely due to CYP2C19 inhibition, might contribute to some AEs, especially somnolence, but also to CBD clinical effectiveness. Cannabidivarin (CBDV), the propyl analogue of CBD, showed anti-convulsant properties in pre-clinical studies, but a plant-derived, purified proprietary formulation of CBDV recently failed the Phase II RCT in patients with uncontrolled focal seizures

Decoherence by Correlated Noise and Quantum Error Correction

We study the decoherence of a quantum computer in an environment which is inherently correlated in time and space. We first derive the nonunitary time evolution of the computer and environment in the presence of a stabilizer error correction code, providing a general way to quantify decoherence for a quantum computer. The general theory is then applied to the spin-boson model. Our results demonstrate that effects of long-range correlations can be systematically reduced by small changes in the error correction codes.Comment: 4 pages, 1 figure, Phys. Rev. Lett. in pres

Synthesis and application of zeolite and glass fiber supported zero valent iron nanoparticles as membrane component for removal nitrate and Cr (+6) ions

In the present paper the synthesis and characterization of zeolite and glass fiber supported zero valent iron nanoparticles (Ze-ZVI, GF-ZVI NPs) are reported.ZVI, Ze-ZVI and GF-ZVI NPs size, composition and morphology were characterized by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), Energy Dispersive Spectroscopy (EDS). Synthesized nanostructures were tested as reducing agents of nitrate and hexavalent Chromium. Batch experiments were carried for revealing of efficacy of prepared nanomaterials (ZE-ZVI NPs and GF-ZVI NPs). Nitrate removal efficiency (at initial concentration 50 mg/mL) was rapidly increased from 26% to 76% for GF-ZVI NPs at 60-240 min time interval for and from 34% to 90% for ZE-ZVI NPs at the same time interval.Also was studied the efficacy of prepared nanostructures ZE-ZVI and ZE-ZVI NPs as membrane component with 5% of ZVI NPS weight contentfor the removal of nitrate from water solution that made 85% for ZE-ZVI NPs and 76% for GF-ZVI NPs, respectively. The results of this study indicate that the application of GF-ZVI and ZE-ZVI NPs as membrane component is advantageous because it allows to prevent the additional pollution of treated solution caused by unreacted ZVI NPs

The characterization, management, and future considerations for ErbB-family TKI-associated diarrhea.

PurposeDiarrhea is recognized as a common adverse event associated with tyrosine kinase inhibitors (TKIs), with those targeting the ErbB family of receptors being associated with the highest rate of diarrhea.MethodsThis paper reviews data on the incidence, timing, and duration of diarrhea associated with US Food and Drug Administration-approved ErbB family-targeted TKIs from the published literature, and sets forth recommendations for management.ResultsIn the absence of anti-diarrheal prophylaxis the incidence of any-grade diarrhea varies and typically occurs early during the course of treatment. Although it is difficult to determine if the incidence and severity of diarrhea is related to inhibition of a particular kinase target because of the multi-targeted and overlapping activity of many agents, evidence suggests that second-generation TKIs with broader target profiles (i.e., afatinib, lapatinib, neratinib) result in a higher incidence of diarrhea compared with highly specific first- (erlotinib, gefitinib) or third- (osimertinib) generation agents. The mechanisms responsible for TKI-associated diarrhea are not fully understood and are likely multi-factorial, involving dysregulated ion transport, inflammation, and mucosal injury. Management strategies have been developed-and continue to be refined-to prevent and reduce the severity and duration of TKI-associated diarrhea. For agents associated with more significant symptoms, anti-diarrheal prophylaxis reduces the incidence and severity of diarrhea, and ongoing studies are evaluating specific strategies to further reduce incidence and duration of TKI-associated diarrhea.ConclusionsContinued investigations into risk factors and pharmacogenomic markers for diarrhea may further improve management of this common toxicity

Information-flux approach to multiple-spin dynamics

We introduce and formalize the concept of information flux in a many-body register as the influence that the dynamics of a specific element receive from any other element of the register. By quantifying the information flux in a protocol, we can design the most appropriate initial state of the system and, noticeably, the distribution of coupling strengths among the parts of the register itself. The intuitive nature of this tool and its flexibility, which allow for easily manageable numerical approaches when analytic expressions are not straightforward, are greatly useful in interacting many-body systems such as quantum spin chains. We illustrate the use of this concept in quantum cloning and quantum state transfer and we also sketch its extension to non-unitary dynamics.Comment: 7 pages, 4 figures, RevTeX

Electroantennographic responses of Aromia bungii (Faldermann, 1835) (Coleoptera, Cerambycidae) to a range of volatile compounds

The red-necked longhorn beetle, Aromia bungii, is one of the most damaging pests of stone fruit trees. Native to the south-eastern Palearctic and Oriental regions, it invaded and is established to some extent in the Campania Region (Southern Italy). In several cerambycid species, volatile organic compounds (VOCs) have been shown to play a role in mate and host plant location. Increasing EAG amplitudes from the basal to the distal antennal segments were recorded in response to six selected plant volatiles. From the distal flagellomeres, the largest EAG responses (>0.8 mV) were elicited by 2-hexanol, octanal, sulcatone, guaiacol, sulcatol, 2,4-dimethyl-3-hexanol, 2,4-dimethyl-2-hexanone, heptanal, nonanal, (Z)-3-hexenol, and 1-heptanol in both sexes, and by linalool, (E)-2-heptenal, 1-octen-3-ol, (E)-2-octenal, 3-octanol, (E)-2-octen-1-ol, alfa-phellandrene, and alfa-terpinene in males. The olfactory system of both sexes proved to be sensitive to changes in stimulus concentration and compound structure. This study demonstrates the capability of A. bungii males and females to detect and discriminate among a wide range of VOCs and provides a basis for further olfactometer and field trapping experiments aimed at identifying behaviorally-active compounds useful for the implementation of semiochemical-based control strategies for this pest

Therapeutic approach in glioblastoma multiforme with primitive neuroectodermal tumor components: case report and review of the literature

Glioblastoma multiforme (GBM) is the most common and aggressive malignant glioma that is treated with first-line therapy, using surgical resection followed by local radiotherapy and concomitant/adjuvant temozolomide (TMZ) treatment. GBM is characterised by a high local recurrence rate and a low response to therapy. Primitive neuroectodermal tumour (PNET) of the brain revealed a low local recurrence rate; however, it also exhibited a high risk of cerebrospinal fluid (CSF) dissemination. PNET is treated with surgery followed by craniospinal irradiation (CSI) and platinum-based chemotherapy in order to prevent CSF dissemination. GBM with PNET-like components (GBM/PNET) is an emerging variant of GBM, characterised by a PNET-like clinical behaviour with an increased risk of CSF dissemination; it also may benefit from platinum-based chemotherapy upfront or following failure of GBM therapy. The results presented regarding the management of GBM/PNET are based on case reports or case series, so a standard therapeutic approach for GBM/PNET is not defined, constituing a challenging diagnostic and therapeutic dilemma. In this report, a case of a recurrent GBM/PNET treated with surgical resection and radiochemotherapy as Stupp protocol, and successive platinum-based chemotherapy due to the development of leptomeningeal dissemintation and an extracranial metastasis, is discussed. A review of the main papers regarding this rare GBM variant and its therapeutic approach are also reported. In conclusion, GBM/PNET should be treated with a multimodal approach including surgery, chemoradiotherapy, and/or the early introduction of CSI and platinum-based chemotherapy upfront or at recurrence

Defective B-cell proliferation and maintenance of long-term memory in patients with chronic granulomatous disease

Background: Chronic granulomatous disease (CGD) is a primary immune deficiency characterized by a defect in reactive oxygen species production. Although the effect of CGD mainly reflects on the phagocytic compartment, B-cell responses are also impaired in patients with CGD. Objective: We sought to investigate how defective gp91phox expression in patients with CGD and CGD carriers might affect the B-cell compartment and maintenance of long-term memory. Methods: We studied the B-cell compartment of patients with CGD in terms of phenotype and ability to produce reactive oxygen species and proliferate on stimuli differently directed to the B-cell receptor and Toll-like receptor 9. We further studied their capacity to maintain long-term memory by measuring cellular and serologic responses to measles. Results: We show that the memory B-cell compartment is impaired among patients with CGD, as indicated by reduced total (CD191CD271) and resting (CD191CD271CD211) memory B cells in parallel to increased naive (CD191CD272IgD1) B-cell frequencies. Data on CGD carriers reveal that such alterations are related to gp91phox expression. Moreover, proliferative capabilities of B cells on selective in vitro stimulation of B-cell receptor or Toll-like receptor 9 pathways were reduced in patients with CGD compared with those seen in age-matched healthy control subjects. Significantly lower measles-specific antibody levels and antibody-secreting cell numbers were also observed, indicating a poor ability to maintain long-term memory in these patients. Conclusion: Altogether, our data suggest that patients with CGD present a defective B-cell compartment in terms of frequencies of memory B cells, response to in vitro stimulation, and maintenance of long-term antigen-specific memory