Preventive Therapies for Chronic Migraine Balfagón, Gloria; Blanco-Rivero, Javier; Márquez-Rodas, Iván ...
The New England journal of medicine,
02/2018, Letnik:
378, Številka:
8
Journal Article
Recenzirano
To the Editor:
In the November 30 issue, two groups of researchers report the results of phase 3 clinical trials of drugs for the prevention of migraine. Silberstein et al.
1
describe the efficacy of ...fremanezumab, a monoclonal antibody targeting calcitonin gene–related peptide (CGRP), and Goadsby et al.
2
describe the efficacy of the anti-CGRP receptor erenumab. With respect to the effects of these two drugs, we note that CGRP is a potent endogenous vasodilator. Our group has been investigating the role of CGRP in vascular tone in experimental models. CGRP seems to play a larger role in altering vascular tone in . . .
Preventive Therapies for Chronic Migraine Goadsby, Peter J; Picard, Hernan; Mikol, Daniel D
The New England journal of medicine,
02/2018, Letnik:
378, Številka:
8
Journal Article
Patients with schizophrenia suffer from perceptual visual deficits. It remains unclear whether those deficits result from an isolated impairment of a localized brain process or from a more diffuse ...long-range dysconnectivity within the visual system. We aimed to explore, with a reading paradigm, the functioning of both ventral and dorsal visual pathways and their interaction in schizophrenia. Patients with schizophrenia and control subjects were studied using event-related functional MRI (fMRI) while reading words that were progressively degraded through word rotation or letter spacing. Reading intact or minimally degraded single words involves mainly the ventral visual pathway. Conversely, reading in non-optimal conditions involves both the ventral and the dorsal pathway. The reading paradigm thus allowed us to study the functioning of both pathways and their interaction.
Behaviourally, patients with schizophrenia were selectively impaired at reading highly degraded words. While fMRI activation level was not different between patients and controls, functional connectivity between the ventral and dorsal visual pathways increased with word degradation in control subjects, but not in patients. Moreover, there was a negative correlation between the patients' behavioural sensitivity to stimulus degradation and dorso-ventral connectivity. This study suggests that perceptual visual deficits in schizophrenia could be related to dysconnectivity between dorsal and ventral visual pathways.
•We explored ventral and dorsal visual pathways and their interaction in schizophrenia.•Patients were selectively impaired when both visual pathways are required.•Ventral and dorsal pathways were normally activated in patients.•Connectivity between visual pathways was not modulated in patients.•Visual deficits in schizophrenia could be related to dysconnectivity between visual pathways.
Abstract Background Concomitant painful physical symptoms in depressive patients frequently impair functioning and failure to treat these symptoms may adversely impact treatment outcomes of ...depression. Early vs. conventional switch of antidepressants were compared in patients with major depressive disorder (MDD) and moderate to severe pain. Method Pre-specified subgroup analysis of a 16-week, randomized, double-blind clinical study on MDD patients with >30 mm overall pain visual analog scale (VAS). Patients not achieving 30% reduction Hamilton Depression Rating Scale (HAM-D) after 4 weeks escitalopram (10 mg/day) were randomized to duloxetine 60–120 mg/day ( early switch) or continued on escitalopram ( conventional switch) with non-responders at week 8 switching to duloxetine. Endpoints were time to confirmed response and remission, VAS pain severity, and Sheehan disability scale (SDS). Switch strategies were compared using Kaplan–Meier, logistic regression, and repeated measures analyses. Results No differences between early and conventional switching were found in time to confirmed response after randomization (3.9 vs. 4.1 weeks, p =0.511) or remission (6.0 vs. 8.0 weeks, p =0.238). Significantly lower VAS mean pain levels at for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time being awake in pain were found for patients in the early switching group. Time to achieving normal functioning (SDS total score <6) was shorter in the early switching group ( p =0.042). Safety results were comparable between switch strategies. Conclusions In MDD patients with moderate to severe painful physical symptoms not improving after 4 weeks of treatment with escitalopram, an earlier switch to duloxetine may lead to better pain and functional outcomes.
Duloxetine is a serotonin and norepinephrine reuptake inhibitor approved in the European Union for the treatment of major depressive disorder, generalized anxiety disorder, and diabetic peripheral ...neuropathic pain in adults. This study aimed to assess the real-world conditions of duloxetine use in France. Between April 2009 and January 2010, 290 dispensing pharmacies, randomly selected from a nationally representative list, included 1,104 patients who presented a duloxetine prescription and consented to the study. Demographic, clinical, and prescription data were extracted from pharmacy records and requested from prescribing physicians. Of the 294 patients with full data available, the mean age (standard deviation) was 54.5 (13.5) years; 74.1% were female; and 86.7% presented with a renewal prescription. 73.5% of patients had major depressive disorder; 3.4% generalized anxiety disorder; and 3.4% diabetic peripheral neuropathic pain. Overall, 78.2% (95% CI: 73.1; 82.8) of patients received duloxetine for an EU-approved indication; 95.2% (95% CI: 92.1; 97.4) of patients had no contra-indication to duloxetine; and 99.0% (95% CI: 97.0; 99.8) received an approved dose. Combining these three criteria, the overall approved use of duloxetine was 73.7% (95% CI: 68.3; 78.7). The strengths and limitations of the study design are discussed.
Postmortem muscle cells die through apoptosis Becila, Samira; Herrera-Mendez, Carlos Hernan; Coulis, Gerald ...
European food research & technology,
2010/7, Letnik:
231, Številka:
3
Journal Article
Recenzirano
Several reports suggested the activation of caspases in postmortem muscle implicating the onset of a caspase-dependent cell death process after animal bleeding. It has been further well established ...that apoptosis and necrosis are the two major cell death pathways. The questions addressed in the present work were as follows: (a) in postmortem muscle, do cells die as in vivo? and (b) if so, by which dying process this goal is achieved? Selected hallmarks of apoptosis (phosphatidylserine externalization (PS), cell shrinkage, actin degradation) were analyzed in postmortem rat muscles and compared to usual cell behavior in apoptotic and necrotic processes. Results presented clearly demonstrate a rapid PS externalization and cell shrinkage extending during the first 24 h postexsanguination together with a progressive degradation of cytoskeletal and thin filaments of actin. It was therefore concluded that, in postmortem muscle, cells commit suicide soon after animal bleeding through apoptosis.
