Do Inhaled Corticosteroids Cause an Increased Risk for Developing or Worsening a Patient’s Diabetes Mellitus?

OBJECTIVE The objective of this selective EBM review is to determine whether or not inhaled corticosteroids (ICS) cause an increased risk for developing or worsening a patient’s diabetes mellitus (DM). STUDY DESIGN Review of three English language primary studies published in 1993, 2009 and 2010. DATA SOURCES A nested case-control analysis, a randomized control trial and a prospective randomized, doubleblind, double-dummy, placebo-controlled, crossover investigation comparing the onset and/or progression of diabetes mellitus in patients using ICS were found using Ovid MEDLINE, PubMed, and Cochrane databases. OUTCOMES MEASURED Incidence or progression of diabetes was measured using a combination of oral glucose tolerance test, serum insulin levels, HGbA1c levels, and fasting glucose levels. RESULTS Faul had 70% of patients that experienced some increase in HGbA1c levels, but none that were statistically significant. Kiviranta had very slight increases in blood glucose when compared to the patient’s baseline measurements. Suissa had a 34% increase in the onset or progression to insulin use of diabetic patients. CONCLUSIONS While all of the studies showed an increase in the incidence or progression of diabetes in patients taking ICS, none of the increases were significant enough to preclude diabetics from taking ICS as needed. Careful monitoring of a patient with diabetes needing an ICS is warranted to prevent loss of diabetes control. Additionally, a baseline HGbA1c level on a patient newly prescribed an ICS might be beneficial

Experimental treatment options in absence epilepsy

Contains fulltext : 182124.pdf (preprint version ) (Open Access)Background: The benign character of absence epilepsy compared to other genetic generalized epilepsy syndromes has often hampered the search for new treatment options. Absence epilepsy is most often treated with ethosuximide or valproic acid. However, both drugs are not always well tolerated or fail, and seizure freedom for a larger proportion of patients remains to be achieved. The availability of genuine animal models of epilepsy does allow to search for new treatment options not only for absence epilepsy perse but also for other genetic - previously called idiopathic - forms of epilepsy. The recent discovery of a highly excitable cortical zone in these models is considered as a new therapeutic target area. Methods: Here, we provide an overview regarding the search for new therapeutical options as has been investigated in the genetic rodent models (mainly WAG/Rij and GAERS) including drugs and whether antiepileptogenesis can be achieved, various types of electrical and optogenetical invasive stimulations, different types of non-invasive stimulation and finally whether absence seizures can be predicted and prevented. Results: Many factors determine either the cortical and or thalamic excitability or the interaction between cortex and thalamus and offer new possibilities for new anti-absence drugs, among others metabotropic glutamatergic positive and negative allosteric modulators. The inhibition of epileptogenesis by various drugs with its widespread consequences seems feasible, although its mechanisms remain obscure and seems different from the anti-absence action. Surgical intervention on the cortical zone initiating seizures, either with radiosurgery using synchrotron-generated microbeams, or ablation techniques might reduce spike-and-wave discharges in the rodent models. High frequency electrical subcortical or cortical stimulation might be a good way to abort ongoing spike-and-wave discharges. In addition, possibilities for prevention with real-time EEG analyses in combination with electrical stimulation could also be a way to fully control these seizures. Conclusion: Although it is obvious that some of these treatment possibilities will not be used for absence epilepsy and/or need to be further developed, all can be considered as proof of principle and provide clear directives for further developments

Species-specific susceptibility to cannabis-induced convulsions

Background and Purpose. Numerous claims are made for cannabis' therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both 9-tetrahydrocannabinol ( 9-THC), variously reported to be pro- and anti-convulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different 9-THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling. Experimental Approach. Cannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography-telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract-treated rats, and treatment-naïve rat, mouse, chicken, dog and human tissue. Key Results. Prolonged exposure to cannabis extracts caused spontaneous, generalised seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher 9-THC, but lower 11-hydroxy-THC (11-OH-THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB1R)-mediated signalling. Profiling CB1R expression, basal activity, extent of activation and sensitivity to 9-THC suggested interspecies differences in eCB signalling, being more pronounced in a species that exhibited cannabis extract-induced seizures (rat) than a species that did not (dog). Conclusion and Implications. Sustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis-induced convulsions from animal models

A obesidade infantil: um olhar sobre o contexto familiar, escolar e da mídia

Background and Objectives: The increasing obesity worldwide allocates this problem as a global epidemic, emphasizing the same as a public health problem. Obesity also arises as a childhood disease, requiring health professionals, preventive actions to achieve the whole context in which children and adults are inserted. From this theme aimed to discuss the problem of childhood obesity and its relationship with three agents influencing the lifestyles of children with overweight and obesity: audiovisual media, family relationships and academic institutions.Content: literature review article. They were consulted in search engines (SciELO and PubMed) articles that had in it context at least two of the following descriptors: academic institutions, family relations, audiovisual media and child obesity. It was considered as time cutting the period 2009-2013.Conclusion: there was the need for public policies that regulate advertising aimed at children, adapting them to the educational and preventive profile. In addition, it was found that the school plays a fundamental role in the practice of healthy eating habits. It is clear, therefore, the need to adapt to this reality, and the family's role to mediate and control such actions. Keywords: Video-Audio Media. Family Relations. Schools. Pediatric Obesity.Justificativa e Objetivos: O crescente aumento da obesidade em nível mundial aloca este problema como uma epidemia global, enfatizando a mesma como um problema de saúde pública. A obesidade também se coloca como uma doença infantil, exigindo dos profissionais da saúde, ações preventivas que atinjam todo o contexto em que crianças e adultos estejam inseridos. A partir desta temática, objetivou-se discutir a problemática da obesidade infantil e a sua relação com três agentes que influenciam o estilo de vida de escolares com sobrepeso e obesidade: mídia audiovisual, relações familiares e instituições acadêmicas. Conteúdo: Artigo de revisão de literatura onde foram consultados em sites de busca (Scielo e PubMed) artigos que tivessem no seu contexto no mínimo dois dos seguintes descritores: instituições acadêmicas, relações familiares, mídia audiovisual e obesidade infantil. Considerou-se como recorte temporal o período de 2009 a 2013. Conclusão: verificou-se a necessidade de políticas públicas que normatizem propagandas destinadas ao público infantil, adequando-as ao perfil educativo preventivo. Além disso, constatou-se que a escola exerce papel fundamental na prática de hábitos alimentares saudáveis. Percebe se, assim, a necessidade de adaptação a essa realidade, tendo a família o papel de mediar e controlar tais ações. DESCRITORES: Mídia audiovisual. Relações familiares. Instituições acadêmicas. Obesidade infantil

The role of the cortico-thalamo-cortical system in absence epilepsy: Unraveling brain networks using multi-site local field potential recordings, dynamical signal analysis and deep brain stimulation

Contains fulltext : 115722.pdf (publisher's version ) (Open Access)Radboud Universiteit Nijmegen, 11 november 2013Promotor : Luijtelaar, E.L.J.M. van289 p

The role of thalamic nuclei in genetic generalized epilepsies

There is no doubt on the participation of the thalamus in the various types of genetic generalized epilepsies as evidenced by multiple non-invasive imaging studies in humans as well as invasive studies in animal models of GGE. Based on human and mostly animal data gathered in early 2000 a so called ‘three compartment model’ on seizure generation was proposed conceptualizing the existence of a hyperexcitable cortical seizure onset zone providing excitation to relay cells of the relay thalamus and the inhibitory reticular thalamic nucleus (RTn). The interplay of corticothalamic excitation and feedforward inhibition via RTn is supposed to entrain thalamic relay neurons into synchronous, oscillatory activity for SWD sustainment. With the emergence of more fine-tuned experimental techniques and analyses, however, it becomes apparent that this model is too simplistic as the thalamus cannot be regarded as unity. Rather, different thalamic nuclei, being integrated in different thalamocortical and other subcortical subloops, need to be differentiated, which take over different functions for seizure generation, generalization and maintenance. Moreover, these networks are not necessarily the same for different classes of patients with GGE and can even be antagonistic between seizure types. This review will summarize data concerning different nuclei and their participation in GGE in order to extend this model and create a more detailed concept on seizure generation, generalization and maintenance

The Dynamics Of Cortico-Thalamo-Cortical Network Interactions At The Transition To Spike-Wave Discharges

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Thalamic stimulation in absence epilepsy

Purpose The site specific effects of two different types of electrical stimulation of the thalamus on electroencephalic epileptic activity as generated in the cortico-thalamo-cortical system were investigated in genetic epileptic WAG/Rij rats, a well characterized and validated absence model. Methods First, 12 male rats received low frequency (double-pulse pairs of 2.5 Hz, 150 μA intensity and 30 s inter-pair-interval) open-loop stimulation to either the Ventral-Postero-Medial (VPM) or the Anterior Thalamic Nucleus (ATN) for 8 h. Second, rats received high frequency (130 Hz, pulse train of 1 s) closed-loop stimulation applied to either VPM or ATN whenever a spike-wave discharge (SWD) was automatically detected. Results Low frequency stimulation induced 8 Hz SWD-like afterdischarges (AD). AD were frequently seen in VPM but rarely in ATN stimulated rats. AD, recorded in cortex and thalamus, showed a strong temporal coherence (visually assessed) and opposite spike polarities. Properties of AD and spontaneous SWD were equally affected by the stimulation. Closed-loop high frequency stimulation disrupted spontaneous SWD with no difference between ATN and VPM stimulated rats. 89% of SWD could be disrupted leading to a decrease in average SWD duration from 9 to 1.5 s. Conclusion Low frequency stimulation induced AD, which strongly mimic SWD. Moreover, the effects were site-specific. High frequency thalamic stimulation disrupts ongoing SWD probable by interfering with the slow firing pattern of cortico-thalamo-cortical neurons seen during SWD cycle. The absence of stimulation site specificity for high frequency stimulation might be due to the fact that stimulation only started on average 1 s after SWD onset when SWD are already fully expressed in the bidirectional cortico-thalamo-cortical resonance system