The Use of Antiepileptic Drugs (AEDs) for the Treatment of Pediatric Aggression and Mood Disorders

Aggressive symptomatology presents across multiple psychiatric, developmental, neurological and behavioral disorders, complicating the diagnosis and treatment of the underlying pathology. Anti-Epileptic Drugs (AEDs) have become an appealing alternative in the treatment of aggression, mood lability and impulsivity in adult and pediatric populations, although few controlled trials have explored their efficacy in treating pediatric populations. This review of the literature synthesizes the available data on ten AEDs—valproate, carbamazepine, oxcarbazepine, phenytoin, lamotrigine, topiramate, levetiracetam, zonisamide, gabapentin and tiagabine—in an attempt to assess evidence for the efficacy of AEDs in the treatment of aggression in pediatric populations. Our review revealed modest evidence that some of the AEDs produced improvement in pediatric aggression, but controlled trials in pediatric bipolar disorder have not been promising. Valproate is the best supported AED for aggression and should be considered as a first line of treatment. When monotherapy is insufficient, combining an AED with either lithium or an atypical anti-psychotic can result in better efficacy. Additionally, our review indicates that medications with predominately GABA-ergic mechanisms of action are not effective in treating aggression, and medications which decrease glutaminergic transmission tended to have more cognitive adverse effects. Agents with multiple mechanisms of action may be more effective

Influence of dynamical scattering in crystalline poly„vinylidene

The effective Debye temperature of poly(vinylidene fluoride-trifluoroethylene) copolymers was measured using photoemission and neutron diffraction techniques. An effective Debye temperature of 53611K is obtained from the photoemission data and 6963.5K from neutron diffraction measurements. This effective Debye temperature is a consequence of the temperature-dependent dynamic motions perpendicular to the surface of these crystalline polymer films

Influence of dynamical scattering in crystalline poly„vinylidene

The effective Debye temperature of poly(vinylidene fluoride-trifluoroethylene) copolymers was measured using photoemission and neutron diffraction techniques. An effective Debye temperature of 53611K is obtained from the photoemission data and 6963.5K from neutron diffraction measurements. This effective Debye temperature is a consequence of the temperature-dependent dynamic motions perpendicular to the surface of these crystalline polymer films

Cystatin C deficiency in human atherosclerosis and aortic aneurysms

The pathogenesis of atherosclerosis and abdominal aortic aneurysm involves breakdown of the elastic laminae. Elastolytic cysteine proteases, including cathepsins S and K, are overexpressed at sites of arterial elastin damage, but whether endogenous local inhibitors counterbalance these proteases is unknown. We show here that, whereas cystatin C is normally expressed in vascular wall smooth muscle cells (SMCs), this cysteine protease inhibitor is severely reduced in both atherosclerotic and aneurysmal aortic lesions. Furthermore, increased abdominal aortic diameter among 122 patients screened by ultrasonography correlated inversely with serum cystatin C levels. In vitro, cytokine-stimulated vascular SMCs secrete cathepsins, whose elastolytic activity could be blocked when cystatin C secretion was induced by treatment with TGF-β1. The findings highlight a potentially important role for imbalance between cysteine proteases and cystatin C in arterial wall remodeling and establish that cystatin C deficiency occurs in vascular disease

Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction

Matrix metalloproteinase-9 (MMP-9) is prominently overexpressed after myocardial infarction (MI). We tested the hypothesis that mice with targeted deletion of MMP9 have less left ventricular (LV) dilation after experimental MI than do sibling wild-type (WT) mice. Animals that survived ligation of the left coronary artery underwent echocardiographic studies after MI; all analyses were performed without knowledge of mouse genotype. By day 8, MMP9 knockout (KO) mice had significantly smaller increases in end-diastolic and end-systolic ventricular dimensions at both midpapillary and apical levels, compared with infarcted WT mice; these differences persisted at 15 days after MI. MMP-9 KO mice had less collagen accumulation in the infarcted area than did WT mice, and they showed enhanced expression of MMP-2, MMP-13, and TIMP-1 and a reduced number of macrophages. We conclude that targeted deletion of the MMP9 gene attenuates LV dilation after experimental MI in mice. The decrease in collagen accumulation and the enhanced expression of other MMPs suggest that MMP-9 plays a prominent role in extracellular matrix remodeling after MI

Lattice-Stiffening Transition in Copolymer Films of Vinylidene Fluoride (70%) with Trifluoroethylene (30%)

We report the discovery of a compressibility phase transition at 160 K in crystalline copolymer films of vinylidene fluoride ( 70%) with trifluoroethylene ( 30%). This phase transition is distinct from the known bulk ferroelectric-paraelectric phase transition at 353 K and surface ferroelectric phase transition at 295 K. The new phase transition is characterized by an increase in the effective Debye temperature from 48 to 245 K along the 〈010〉 direction as the temperature falls below 160 K. This phase transition is evident in neutron scattering, x-ray diffraction, angle-resolved photoemission, and in the dipole active phonon modes in electron energy-loss spectroscopy

Storage oil hydrolysis during early seedling growth

Storage oil breakdown plays an important role in the life cycle of many plants by providing the carbon skeletons that support seedling growth immediately following germination. This metabolic process is initiated by lipases (EC: 3.1.1.3), which catalyze the hydrolysis of triacylglycerols (TAGs) to release free fatty acids and glycerol. A number of lipases have been purified to near homogeneity from seed tissues and analysed for their in vitro activities. Furthermore, several genes encoding lipases have been cloned and characterised from plants. However, only recently has data been presented to establish the molecular identity of a lipase that has been shown to be required for TAG breakdown in seeds. In this review we briefly outline the processes of TAG synthesis and breakdown. We then discuss some of the biochemical literature on seed lipases and describe the cloning and characterisation of a lipase called SUGAR-DEPENDENT1, which is required for TAG breakdown in Arabidopsis thaliana seeds

Phase I and pharmacokinetic study of DE-310 in patients with advanced solid tumors

PURPOSE: To assess the maximum-tolerated dose, toxicity, and pharmacokinetics of DE-310, a macromolecular prodrug of the topoisomerase I inhibitor exatecan (DX-8951f). in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Patients received DE-310 as a 3-hour infusion once every 2 weeks (dose, 1.0-2.0 mg/m(2)) or once every 6 weeks (dose, 6.0-9.0 mg/m(2)). Because pharmacokinetics revealed a drug terminal half-life exceeding the 2 weeks administration interval, the protocol was amended to a 6-week interval between administrations also based on available information from a parallel trial using an every 4 weeks schedule. Conjugated DX-8951 (the carrier-linked molecule), and the metabolites DX-8951 and glycyl-DX-8951 were assayed in various matrices up to 35 days post first and second dose. RESULTS: Twenty-seven patients were enrolled into the study and received a total of 86 administrations. Neutropenia and grade 3 thrombocytopenia, and grade 3 hepatotoxicity with veno-occlusive disease, were dose-limiting toxicities. Other hematologic and nonhematologic toxicities were mild to moderate and reversible. The apparent half-life of conjugated DX-8951, glycyl-DX-8951, and DX-8951 was 13 days. The area under the curve ratio for conjugated DX-8951 to DX-8951 was 600. No drug concentration was detectable in erythrocytes, skin, and saliva, although low levels of glycyl-DX-8951 and DX-8951 were detectable in tumor biopsies. One patient with metastatic adenocarcinoma of unknown primary achieved a histologically proven complete remission. One confirmed partial remission was observed in a patient with metastatic pancreatic cancer and disease stabilization was noted in 14 additional patients. CONCLUSIONS: The recommended phase II dose of DE-310 is 7.5 mg/m(2) given once every 6 weeks. The active moiety DX-8951 is released slowly from DE-310 and over an extended period, achieving the desired prolonged exposure to this topoisomerase I inhibitor

Reliability and Validity of the Supports Intensity Scale (SIS) Measured in Adults with Physical Disabilities

The objective of this study was to investigate the internal consistency and the construct validity of the Dutch version of the Supports Intensity Scale (SIS-NL1.0; Buntinx 2006) in individuals with physical disabilities (N = 65). To investigate the construct validity, the relationship between SIS subscales and practical skills (Barthel Index; BI) was calculated. Support was provided for the internal consistency. The SIS subscales (except Behavior) had moderate to high intercorrelations and the SIS was able to discriminate between groups with different number of disabilities. However, weak relationships were found between the BI and four out of eight SIS subscales. For people with physical disabilities, future revisions of the SIS should also take into consideration limitations in practical skills in other support domains

The 2010 Canadian Cardiovascular Society guidelines for the diagnosis and management of heart failure update: Heart failure in ethnic minority populations, heart failure and pregnancy, disease management, and quality improvement/assurance programs

Since 2006, the Canadian Cardiovascular Society heart failure (HF) guidelines have published annual focused updates for cardiovascular care providers. The 2010 Canadian Cardiovascular Society HF guidelines update focuses on an increasing issue in the western world - HF in ethnic minorities - and in an uncommon but important setting - the pregnant patient. Additionally, due to increasing attention recently given to the assessment of how care is delivered and measured, two critically important topics - disease management programs in HF and quality assurance - have been included. Both of these topics were written from a clinical perspective. It is hoped that the present update will become a useful tool for health care providers and planners in the ongoing evolution of care for HF patients in Canada. © 2010 Pulsus Group Inc. All rights reserved