Emerging roles for ion channels in ovarian cancer: Pathomechanisms and pharmacological treatment

Ovarian cancer (OC) is the deadliest gynecologic cancer, due to late diagnosis, development of platinum resistance, and inadequate alternative therapy. It has been demonstrated that membrane ion channels play important roles in cancer processes, including cell proliferation, apop-tosis, motility, and invasion. Here, we review the contribution of ion channels in the development and progression of OC, evaluating their potential in clinical management. Increased expression of voltage-gated and epithelial sodium channels has been detected in OC cells and tissues and shown to be involved in cancer proliferation and invasion. Potassium and calcium channels have been found to play a critical role in the control of cell cycle and in the resistance to apoptosis, promoting tumor growth and recurrence. Overexpression of chloride and transient receptor potential channels was found both in vitro and in vivo, supporting their contribution to OC. Furthermore, ion channels have been shown to influence the sensitivity of OC cells to neoplastic drugs, suggesting a critical role in chemotherapy resistance. The study of ion channels expression and function in OC can improve our understanding of pathophysiology and pave the way for identifying ion channels as potential targets for tumor diagnosis and treatment

The treatment of peri-implant diseases: A new approach using HYBENX® as a decontaminant for implant surface and oral tissues

Background: Peri-implantitis is a pathological condition characterized by an inflammatory process involving soft and hard tissues surrounding dental implants. The management of periimplant disease has several protocols, among which is the chemical method HYBENX®. The aim of this study is to demonstrate the efficacy of HYBENX® in the treatment of peri-implantitis and to compare HYBENX® with other chemical agents used in the surgical treatment of peri-implantitis. Methods: The present study included a population of ten subjects with severe peri-implantitis. The procedure used in the study involves the application of HYBENX® after open-flap debridement. Each patient has been followed for 12 months after a single application of the decontaminant agent. Clinical and radiographical parameters were recorded at baseline, 3 months, and 12 months after treatment completion. Results: At baseline, a mean pocket probing depth (PPD) of 7.3 - 0.5 mm and a mean clinical attachment level (CAL) of 8.8 - 0.8 mm was recorded. An average residual PPD of 4.2 - 0.5 mm and a mean CAL of 5.2 - 0.8 mm were observed after 1 year. Additionally, the average of bone gain was about 3.4 mm, with a mean marginal bone level (MBL) change from 5.8 mm (baseline) to 2.4 mm (12 months). In total, 90% of the treated implants reached the success rate after the 1-year follow-up. Only in one case out of ten treated implants was resolution of the disease not achieved. Conclusion: Clinical improvements highlight that the procedure of open-flap debridement (OFD) + HYBENX® may be considered an effective technique in the treatment of peri-implantitis. From the results obtained, it can be concluded that the use of HYBENX® in the surgical treatment of peri-implantitis is promising. Overall, this protocol demands further studies to better understand the role and potential benefits of HYBENX® in the treatment of peri-implantitis

Socio-demographic and clinical characterization of patients with obsessive-compulsive tic-related disorder (OCTD) : An Italian multicenter study

© Copyright by Pacini Editore SrlIn the DSM-5 a new "tic-related" specifier for obsessive compulsive disorder (OCD) has been introduced, highlighting the importance of an accurate characterization of patients suffering from obsessive-compulsive tic-related disorder ("OCTD"). In order to characterize OCTD from a socio-demographic and clinical perspective, the present multicenter study was carried out. The sample consists of 266 patients, divided in two groups with lifetime diagnoses of OCD and OCTD, respectively. OCTD vs OCD patients showed a significant male prevalence (68.5% vs 48.5%; p < .001), a higher rate of psychiatric comorbidities (69.4 vs 50%; p < .001) - mainly with neurodevelopmental disorders (24 vs 0%; p < .001), a lower education level and professional status (middle school diploma: 25 vs 7.6%; full-Time job 44.4 vs 58%; p < .001). Moreover, OCTD vs OCD patients showed significantly earlier age of OCD and psychiatric comorbidity onsets (16.1 ± 10.8 vs 22.1 ± 9.5 years; p < .001, and 18.3 ± 12.8 vs 25.6 ± 9.4: p < .001, respectively). Patients with OCTD patients were treated mainly with antipsychotic and with a low rate of benzodiazepine (74.2 vs 38.2% and 20.2 vs 31.3%, respectively; p < .001). Finally, OCTD vs OCD patients showed higher rates of partial treatment response (58.1 vs 38%; p < .001), lower rates of current remission (35.5 vs 54.8%; p < .001) and higher rates of suicidal ideation (63.2 vs 41.7%; p < .001) and attempts (28.9 vs 8.3%; p < .001). Patients with OCTD report several unfavorable socio-demographic and clinical characteristics compared to OCD patients without a history of tic. Additional studies on larger sample are needed to further characterize OCTD patients from clinical and therapeutic perspectives.Peer reviewedFinal Published versio

Pathomechanisms of a CLCN1 Mutation Found in a Russian Family Suffering From Becker's Myotonia

Objective: Myotonia congenita (MC) is a rare muscle disease characterized by sarcolemma over-excitability inducing skeletal muscle stiffness. It can be inherited either as an autosomal dominant (Thomsen's disease) or an autosomal recessive (Becker's disease) trait. Both types are caused by loss-of-function mutations in the CLCN1 gene, encoding for ClC-1 chloride channel. We found a ClC-1 mutation, p.G411C, identified in Russian patients who suffered from a severe form of Becker's disease. The purpose of this study was to provide a solid correlation between G411C dysfunction and clinical symptoms in the affected patient. Methods: We provide clinical and genetic information of the proband kindred. Functional studies include patch-clamp electrophysiology, biotinylation assay, western blot analysis, and confocal imaging of G411C and wild-type ClC-1 channels expressed in HEK293T cells. Results: The G411C mutation dramatically abolished chloride currents in transfected HEK cells. Biochemical experiments revealed that the majority of G411C mutant channels did not reach the plasma membrane but remained trapped in the cytoplasm. Treatment with the proteasome inhibitor MG132 reduced the degradation rate of G411C mutant channels, leading to their expression at the plasma membrane. However, despite an increase in cell surface expression, no significant chloride current was recorded in the G411C-transfected cell treated with MG132, suggesting that this mutation produces non-functional ClC-1 chloride channels. Conclusion: These results suggest that the molecular pathophysiology of G411C is linked to a reduced plasma membrane expression and biophysical dysfunction of mutant channels, likely due to a misfolding defect. Chloride current abolition confirms that the mutation is responsible for the clinical phenotype

The ALTCRISS project on board the International Space Station

The Altcriss project aims to perform a long term survey of the radiation environment on board the International Space Station. Measurements are being performed with active and passive devices in different locations and orientations of the Russian segment of the station. The goal is to perform a detailed evaluation of the differences in particle fluence and nuclear composition due to different shielding material and attitude of the station. The Sileye-3/Alteino detector is used to identify nuclei up to Iron in the energy range above 60 MeV/n. Several passive dosimeters (TLDs, CR39) are also placed in the same location of Sileye-3 detector. Polyethylene shielding is periodically interposed in front of the detectors to evaluate the effectiveness of shielding on the nuclear component of the cosmic radiation. The project was submitted to ESA in reply to the AO in the Life and Physical Science of 2004 and data taking began in December 2005. Dosimeters and data cards are rotated every six months: up to now three launches of dosimeters and data cards have been performed and have been returned with the end of expedition 12 and 13.Comment: Accepted for publication on Advances in Space Research http://dx.doi.org/10.1016/j.asr.2007.04.03

Myc depletion induces a pluripotent dormant state mimicking diapause

Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.This work was supported by the FOR2033 and SFB873 funded by the Deutsche Forschungsgemeinschaft (DFG), the Dietmar Hopp Foundation (all to A.T.), and the Wellcome Trust (to A.S.)

Genetic characterization of Erve virus, a European Nairovirus distantly related to Crimean-Congo hemorrhagic fever virus

Erve virus (ERVEV) is a European Nairovirus that is suspected to cause severe headache (thunderclap headache) and intracerebral hemorrhage. The mode of transmission to humans (ticks or mosquitoes) is still unknown. Currently, no standardized testing method for ERVEV exists and only a small partial sequence of the polymerase gene is available. Here, we present the first complete genome sequence of ERVEV S, M, and L segments. Phylogenetic comparison of the amino acid sequence of the L-protein (RNA-dependent RNA polymerase) revealed only 48 % homology to available L-protein sequences of other Nairoviruses like Crimean-Congo hemorrhagic fever virus, Nairobi sheep disease virus, Hazara virus, Kupe virus, and Dugbe virus. Among themselves, these Nairoviruses show 62-89 % homology in the L-protein sequences. Therefore, ERVEV seems to be only distantly related to other Nairoviruses. The new sequence data can be used for the development of diagnostic methods and the identification of the natural vector

Launch of the Space experiment PAMELA

PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10^-8). The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June, 15, 2006 in a 350*600 km orbit with an inclination of 70 degrees. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, Time-of-Flight and rigidity information. Lepton/hadron identification is performed by a Silicon-Tungsten calorimeter and a Neutron detector placed at the bottom of the device. An Anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the Calorimeter, the neutron detector and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives and the performance in the first months after launch.Comment: Accepted for publication on Advances in Space Researc

The Italian National Register of infants with congenital hypothyroidism: twenty years of surveillance and study of congenital hypothyroidism

All the Italian Centres in charge of screening, diagnosis, and follow-up of infants with congenital hypothyroidism participate in the Italian National Registry of affected infants, which performs the nationwide surveillance of the disease. It was established in 1987 as a program of the Health Ministry and is coordinated by the Istituto Superiore di Sanità. The early diagnosis performed by the nationwide newborn screening programme, the prompt treatment and the appropriate clinical management of the patients carried out by the Follow-up Centres, and the surveillance of the disease performed by the National Register of infants with congenital hypothyroidism are the components of an integrated approach to the disease which has been successfully established in our country