Management of epilepsy in elderly

The prevalence of seizures and epilepsy in the elderly is generally underestimated. Epileptic seizures are not a rare occurrence in the elderly and their prevalence increases with age. The clinical manifestations of seizures, the aetiology, the treatment and the psychosocial impact of the epilepsy diagnosis may differ in the elderly. Differential diagnosis with episodes of unconsciousness and/or fall or other non-epileptic manifestations is often difficult. The presence of comorbidities, the polypharmatherapy and the age-related pharmacokinetic changes can represent a problem for the treatment of epilepsy in the elderly, with a higher risk of adverse effects and potentially inappropriate drug interactions. Epileptic seizures in the elderly can have semiological characteristics similar to those of other age groups. On the other hand, the richness of the electroclinical syndromes of childhood and adolescence is not found in the elderly, and, in particular, idiopathic generalized epilepsies are rarely expressed at this age. Symptomatic seizures related to acute structural injury or metabolic causes are particularly frequent. Therapy management of the elderly with an epileptic seizure should concern not only neurologists, but also general practitioners, geriatricians, and cardiologists, therefore involving a wide range of clinical specialties. This review aims to summarize the management of epilepsy in the elderly, reporting also differences in epidemiology, electroclinical features, aetiology and diagnostic procedures

Marine pharmacology in 2009-2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories

Carbon cycling in a Patagonian fjord: Strength of biological vs. physical pump

Póster presentado en la 2nd International Ocean Research Conference, celebrada en Barcelona del 17 al 21 de noviembre de 2014.Understanding the role of the pelagic “biological and physical pump” in carbon cycling is critical to climate change adaptation and mitigation efforts especially in coastal areas characterized by intense biogeochemical cycling. Fjords are among the few coastal regions that appear to be net annual sinks for atmosphericCO2. Vertical profiles of temperature and salinity were collected with a CTD revealing intense vertical structure in the water column that could be summarised as 2 layers with a transition-mixing region .Spatio-temporal sampling of physical and biogeochemical (C system, nutrients, Phyto- and Zooplankton, in situ dissolved pCO2) parameters was conducted in Comau Fjord (Puerto Montt-Chile) during Austral spring from the surface and deep layers. Spatial variation in water column structure in the fjord was minimal, however the depth of the upper layer varies probably depending on the surface-water inputs. Surface waters had significantly lower pCO2 values compared to the atmosphere and deeper water. Concentrations of suspended material and chlorophyll a were higher deeper in the water column, suggesting concentration process of material across the halocline. Overall, concentrations of particulate matter and mesozooplankton (during the study period), were low compared to many mid-latitude regions, and near absent in the vicinity of the 2 rivers entering the fjord. The low surface water pCO2 values suggest negative air-water CO2fluxes predominates within Comau Fjord during Austral spring. This preliminary study suggests that the geochemical properties of watershed and the low [DIC] of surface-water inputs, i.e., the physical pump, seems to play an important role in this region.This work was supported by the project 2013CL0013 funded by the CSIC, Fundacion Endesa and Fundación San Ignacio del Huinay. Funding was also provided by the Spanish Ministry of Sciences and Innovation (JAE DOCTORES 2010 contract for E.P.M., JAE PREDOCTORAL scholarship for S.T. and S.F.) and part-funded bythe European Union (European Social Fund, ESF2007-2013) and the Spanish Ministry for Economy and Competitiveness.Peer Reviewe

Signaling pathways mediating a selective induction of nitric oxide synthase II by tumor necrosis factor alpha in nerve growth factor-responsive cells

BACKGROUND: Inflammation and oxidative stress play a critical role in neurodegeneration associated with acute and chronic insults of the nervous system. Notably, affected neurons are often responsive to and dependent on trophic factors such as nerve growth factor (NGF). We previously showed in NGF-responsive PC12 cells that tumor necrosis factor alpha (TNFα) and NGF synergistically induce the expression of the free-radical producing enzyme inducible nitric oxide synthase (iNOS). We proposed that NGF-responsive neurons might be selectively exposed to iNOS-mediated oxidative damage as a consequence of elevated TNFα levels. With the aim of identifying possible therapeutic targets, in the present study we investigated the signaling pathways involved in NGF/TNFα-promoted iNOS induction. METHODS: Western blotting, RT-PCR, transcription factor-specific reporter gene systems, mutant cells lacking the low affinity p75NTR NGF receptor and transfections of TNFα/NGF chimeric receptors were used to investigate signalling events associated with NGF/TNFα-promoted iNOS induction in PC12 cells. RESULTS: Our results show that iNOS expression resulting from NGF/TNFα combined treatment can be elicited in PC12 cells. Mutant PC12 cells lacking p75NTR did not respond, suggesting that p75NTR is required to mediate iNOS expression. Furthermore, cells transfected with chimeric TNFα/NGF receptors demonstrated that the simultaneous presence of both p75NTR and TrkA signaling is necessary to synergize with TNFα to mediate iNOS expression. Lastly, our data show that NGF/TNFα-promoted iNOS induction requires activation of the transcription factor nuclear factor kappa B (NF-κB). CONCLUSION: Collectively, our in vitro model suggests that cells bearing both the high and low affinity NGF receptors may display increased sensitivity to TNFα in terms of iNOS expression and therefore be selectively at risk during acute (e.g. neurotrauma) or chronic (e.g. neurodegenerative diseases) conditions where high levels of pro-inflammatory cytokines in the nervous system occur pathologically. Our results also suggest that modulation of NFκB-promoted transcription of selective genes could serve as a potential therapeutic target to prevent neuroinflammation-induced neuronal damage

Ptaquiloside, the major carcinogen of bracken fern, in the pooled raw milk of healthy sheep and goats: an underestimated, global concern of food safety

Bracken fern (Pteridium aquilinum) is a worldwide plant containing toxic substances, which represent an important chemical hazard for animals, including humans. Ptaquiloside, 1, a norsesquiterpenoid glucoside, is the major carcinogen of bracken detected in the food chain, particularly in the milk from farm animals. To date, ptaquiloside has been shown in the milk of cows feeding on a diet containing bracken fern. This is the first study that shows the systematic detection of ptaquiloside, 1, and reports its direct quantitation in pooled raw milk of healthy sheep and goats grazing on bracken. Ptaquiloside, 1, was detected by a sensitive method based on the chemical conversion of ptaquiloside, 1, into bromopterosine, 4, following gas chromatography–mass spectrometry (GC–MS) analysis. The presence of ptaquiloside, 1, possibly carcinogenic to humans, in the milk of healthy animals is an unknown potential health risk, thus representing a harmful and potential global concern of food safety

Effects of Azadirachta indica seed kernel extracts on early erythrocytic schizogony of Plasmodium berghei and pro-inflammatory response in inbred mice

Background: Medicinal plant research may contribute to develop new pharmacological control tools for vector borne diseases, such as malaria. Methods: The effects of methanol extracts (ME) obtained from seed kernel of ripe and unripe Azadirachta indica fruits were studied on erythrocytic proliferation of the rodent malaria parasite Plasmodium berghei strain ANKA and on mice pro-inflammatory response, as evaluated by measuring the matrix-metalloproteinase-9 (MMP-9) and tumour necrosis factor (TNF) plasma levels, in two mouse strains (C57BL/6 and BALB/c) which are considered as prototypical of Th1 and Th2 immune response, respectively. Results: ME obtained from seed kernel of unripe Azadirachta indica fruits decreased by about 30% the proportion of erythrocytes infected with the malaria parasite in C57BL/6 mice in the 4 days suppressive test. In this treatment group, MMP-9 and TNF levels were notably higher than those measured in the same mouse strain treated with the anti-malarial drug artesunate, Azadirachta indica kernel extracts from ripe fruits or solvent. In BALB/c mice, treatment with kernel extracts did not influence parasitaemia. MMP-9 and TNF levels measured in this mouse strain were notably lower than those recorded in C57BL/6 mice and did not vary among treatment groups. Conclusions: The effects of the ME on the parasite-host interactions appeared to be mouse strain-dependent, but also related to the ripening stage of the neem fruits, as only the unripe fruit seed kernel extracts displayed appreciable bioactivity

Modulation of Barrier Properties of Monolayer Films from Blends of Polyethylene with Ethylene-co-Norbornene

Flexible monolayer films with modulated diffusional and optical properties were achieved from blends of a LDPE/LLDPE matrix and an ethylene/norbornene copolymer (COC). A significant decrease of O2 and CO2 permeability was observed for cast films with COC content from 5 to 20 wt %. SEM analysis showed that, despite the incompatibility of the blend components, good dispersion and distribution of the COC domains in the PE matrix were achieved; as a consequence, for COC content ranging from 5 to 10 wt % the film transparency results practically unchanged. The UV light transmission decreased on increasing the percentage of COC, which constitutes also a protection against UV radiations. A noticeable improvement was observed in the mechanical properties: adding only 5 wt % of COC, the elastic modulus becomes five times higher than that of the PE matrix. The rheological behaviour of the blends keeps practically unchanged with respect to the matrix, allowing to use the typical LDPE processing conditions. Sustainable inexpensive flexible films answering the packaging requirements of specific categories of food were achieved

Rapid and safe response to low-dose carbamazepine in neonatal epilepsy

To evaluate treatment responses in benign familial neonatal epilepsy (BFNE)

A novel homozygous KCNQ3 loss-of-function variant causes non-syndromic intellectual disability and neonatal-onset pharmacodependent epilepsy

OBJECTIVE: Heterozygous variants in KCNQ2 or, more rarely, KCNQ3 genes are responsible for early-onset developmental/epileptic disorders characterized by heterogeneous clinical presentation and course, genetic transmission, and prognosis. While familial forms mostly include benign epilepsies with seizures starting in the neonatal or early-infantile period, de novo variants in KCNQ2 or KCNQ3 have been described in sporadic cases of early-onset encephalopathy (EOEE) with pharmacoresistant seizures, various age-related pathological EEG patterns, and moderate/severe developmental impairment. All pathogenic variants in KCNQ2 or KCNQ3 occur in heterozygosity. The aim of this work was to report the clinical, molecular, and functional properties of a new KCNQ3 variant found in homozygous configuration in a 9-year-old girl with pharmacodependent neonatal-onset epilepsy and non-syndromic intellectual disability. METHODS: Exome sequencing was used for genetic investigation. KCNQ3 transcript and subunit expression in fibroblasts was analyzed with quantitative real-time PCR and Western blotting or immunofluorescence, respectively. Whole-cell patch-clamp electrophysiology was used for functional characterization of mutant subunits. RESULTS: A novel single-base duplication in exon 12 of KCNQ3 (NM_004519.3:c.1599dup) was found in homozygous configuration in the proband born to consanguineous healthy parents; this frameshift variant introduced a premature termination codon (PTC), thus deleting a large part of the C-terminal region. Mutant KCNQ3 transcript and protein abundance was markedly reduced in primary fibroblasts from the proband, consistent with nonsense-mediated mRNA decay. The variant fully abolished the ability of KCNQ3 subunits to assemble into functional homomeric or heteromeric channels with KCNQ2 subunits. SIGNIFICANCE: The present results indicate that a homozygous KCNQ3 loss-of-function variant is responsible for a severe phenotype characterized by neonatal-onset pharmacodependent seizures, with developmental delay and intellectual disability. They also reveal difference in genetic and pathogenetic mechanisms between KCNQ2- and KCNQ3-related epilepsies, a crucial observation for patients affected with EOEE and/or developmental disabilities