EFFECT OF POTASSIUM CHANNEL MODULATORS IN MOUSE FORCED SWIMMING TEST

1. The effect of intracerebroventricular (i.c.v.) administration of different potassium channel blockers (tetraethylammonium, apamin, charybdotoxin, gliquidone), potassium channel openers (pinacidil, minoxidil, cromakalim) and aODN to mKv1.1 on immobility time was evaluated in the mouse forced swimming test, an animal model of depression. 2. Tetraethylammonium (TEA; 5 μg per mouse i.c.v.), apamin (3 ng per mouse i.c.v.), charybdotoxin (1 μg per mouse i.c.v.) and gliquidone (6 μg per mouse i.c.v.) administered 20 min before the test produced anti-immobility comparable to that induced by the tricyclic antidepressants amitriptyline (15 mg kg(−1) s.c.) and imipramine (30 mg kg(−1) s.c.). 3. By contrast pinacidil (10–20 μg per mouse i.c.v.), minoxidil (10–20 μg per mouse i.c.v.) and cromakalim (20–30 μg per mouse i.c.v.) increased immobility time when administered in the same experimental conditions. 4. Repeated administration of an antisense oligonucleotide (aODN) to the mKv1.1 gene (1 and 3 nmol per single i.c.v. injection) produced a dose-dependent increase in immobility time of mice 72 h after the last injection. At day 7, the increasing effect produced by aODN disappeared. A degenerate mKv1.1 oligonucleotide (dODN), used as control, did not produce any effect in comparison with saline- and vector-treated mice. 5. At the highest effective dose, potassium channels modulators and the mKv1.1 aODN did not impair motor coordination, as revealed by the rota rod test, nor did they modify spontaneous motility as revealed by the Animex apparatus. 6. These results suggest that modulation of potassium channels plays an important role in the regulation of immobility time in the mouse forced swimming test

Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants inLARS1

Purpose: Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Methods: Individuals with biallelic variants in LARS1 were included through an international, multicenter collaboration including novel and previously published patients. Clinical variables were analyzed and functional studies were performed in patient-derived fibroblasts. Results: Twenty-five individuals from 15 families were ascertained including 12 novel patients with eight previously unreported variants. The most prominent clinical findings are recurrent elevation of liver transaminases up to liver failure and encephalopathic episodes, both triggered by febrile illness. Magnetic resonance image (MRI) changes during an encephalopathic episode can be consistent with metabolic stroke. Furthermore, growth retardation, microcytic anemia, neurodevelopmental delay, muscular hypotonia, and infection-related seizures are prevalent. Aminoacylation activity is significantly decreased in all patient cells studied upon temperature elevation in vitro. Conclusion: ILFS1 is characterized by recurrent elevation of liver transaminases up to liver failure in conjunction with abnormalities of growth, blood, nervous system, and musculature. Encephalopathic episodes with seizures can occur independently from liver crises and may present with metabolic stroke

Nitrile oxide [3 + 2] cycloaddition: application to the synthesis of 6-substituted 3(2H)-pyridazinones and 6-substituted 4,5-dihydro-4-hydroxy-3(2H)-pyridazinones

An efficient method for the prepn. of 6-​substituted 3(2H)​-​pyridazinones and 6-​substituted 4,​5-​dihydro-​4-​hydroxy-​3(2H)​-​pyridazinones starting from 3,​5-​disubstituted 4,​5-​dihydroisoxazoles is described. N-​O bond cleavage of the isoxazoline ring promoted by molybdenum hexacarbonyl or by catalytic hydrogenation afforded the α-​hydroxy γ-​keto esters RCOCH2CH(OH)​CO2Et (I, R = Me, Bu, 2-​, 4-​pyridyl, 4-​HOC6H4) which were converted into 6-​substituted 4,​5-​dihydro-​4-​hydroxy-​3(2H)​-​pyridazinones for 6-​substituted 3(2H)​-​pyridazinones on treatment with hydrazine hydrate at room temp. or reflux in high yield starting from I. An intramol. version of this methodol. has been developed to prep. the known antiulcer tricyclic 5H-​[1]​-​benzopyrano[4,​3-​c]​pyridazin-​3(2H)​-​one

Performance Analysis of different arbitration algorithms of the AMBA AHB Bus

paper 35.5, http://www.dac.com/41st/41acceptedpapers.nsf/brows

Alfred Marshall and Fran\ue7ois Perroux: the neglected liaison

The richness Fran\ue7ois Perroux\u2019s economic theories have allowed the literature to highlight several connections between him and other authors. Among the names mentioned in the literature, one economist is conspicuous by his absence: Alfred Marshall. However, the relations between Marshall and Perroux are manifold and are far from accidental: not only because Perroux was a careful reader of Marshall but also and moreover because they both have an important common ground, which affected their perspectives. The main aim of this paper is to inquire into the aspects that characterise Marshall\u2019s and Perroux\u2019s approaches, stressing their affinities and underlining their common roots

J Pediatr Gastroenterol Nutr

OBJECTIVES: The use of semi-elemental diets concerns a small proportion of children on enteral nutrition whose characteristics have never been reported. Our aim was to describe a cohort of patients on home enteral nutrition with Peptamen Junior, including the tolerance and nutritional efficacy of this product. METHODS: We performed a retrospective multicenter survey on a cohort of patients receiving this semi-elemental diet at home between 2010 and 2015 in 14 tertiary pediatric French centers. We recorded at baseline, 3, 6 and 12 months, and then every year the anthropometric characteristics of the patients, indications and modalities of administration of the diet, and the tolerance and adverse events. RESULTS: We recruited 136 patients aged 9.8 +/- 4.4 years at baseline. Mean BMI z-score was -1.0 +/- 1.8; mean height z-score was -1.1 +/- 1.9. The main underlying diseases were digestive (35.3%), neurological (33.1%), and haematological (19.9%). The indications for a semi-elemental diet were failure of another diet in 70 patients (51.9%), severe malnutrition in 19 (14.1%), cystic fibrosis in 11 (8.1%) and switch from parenteral nutrition in 11 (8.1%). Side effects were observed in 39.2% of the patients, and required medical attention in 8.2%. Body mass index improved or remained normal in 88.3% of children. CONCLUSIONS: This semi-elemental diet seems to be well tolerated and efficient in the setting of home enteral nutrition in children with complex diseases featuring malabsorption and/or after failure of polymeric diet