Mutation in \u3ci\u3eATG5\u3c/i\u3e reduces autophagy and leads to ataxia with developmental delay

Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects’ cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health

Changes in cognitive domains during three years in patients with Alzheimer's disease treated with donepezil

<p>Abstract</p> <p>Background</p> <p>The objective was to identify separate cognitive domains in the standard assessment tools (MMSE, ADAS-Cog) and analyze the process of decline within domains during three years in Alzheimer's disease (AD) patients with donepezil treatment.</p> <p>Method</p> <p>AD patients (n = 421) were recruited from a clinical multi-centre study program in Sweden. Patients were assessed every six months during three years. All patients received donepezil starting directly after study entry. After dropouts, 158 patients remained for analyses over three years. Data for the other patients were analysed until they dropped out (4 groups based on length in study).</p> <p>Results</p> <p>Factor analyses of all items suggested that there were three intercorrelated factors: a General, a Memory and a Spatial factor for which we constructed corresponding domains. Overall there was a cognitive improvement at six months followed by a linear drop over time for the three domains. Some group and domain differences were identified. Patients who remained longer in the study had better initial performance and a slower deterioration rate. The early dropouts showed no improvement at six months and many dropped out due to side effects. The other groups displayed a performance improvement at six months that was less pronounced in the Memory domain. Before dropping out, deterioration accelerated, particularly in the Spatial domain.</p> <p>Conclusion</p> <p>The course of illness in the three domains was heterogeneous among the patients. We were not able to identify any clinically relevant correlates of this heterogeneity. As an aid we constructed three algorithms corresponding to the cognitive domains, which can be used to characterize patients initially, identify rapid decliners and follow the course of the disease.</p

Potentiometric Determination of the Stability Constants of Lanthanide Complexes with Iminodiacetic Acid in Water and Dioxane-Water Mixtures

WOS: 000262864700008The protonation constants of iminodiacetic acid (H(2)ida) and the stability constants of its complexes with Nd(III), Sm(III), Gd(III), Dy(III), and Er( III) ions at metal/ligand mole ratios of 1: 1, 1: 2, and 1: 3 at 25 degrees C and 0.1 M ionic strength in aqueous medium and 20%, 45%, and 70% w/w dioxane-water mixtures were determined by the potentiometric method using the BEST computer program. The stability constants of the complexes that formed increased as the dioxane content increased. The stability of all the analogues' complexes, both in aqueous medium and in dioxane-water mixtures, were in the order of Nd(III) < Sm(III) < Gd(III) < Dy(III) < Er(III).Ege UniversityEge University [04FEN065]This work was financially supported by the Research Fund of Ege University (04FEN065)

Effect of analgesia administration timing on early post-operative period characteristics: A randomized, double-blind, controlled study

This study investigated the effect of time of analgesia administration in 64 patients undergoing total abdominal hysterectomy. Patients received standard general anaesthesia and were divided randomly into two equal groups. At the time of fascia closure, patients in the intra-operative (lop) group received 0.5 mg/kg pethidine intravenously. On arrival in the post-anaesthesia care unit, the same dose of pethidine was given to patients in the postoperative (Pop) group. All patients then used a patient-controlled analgesia pump to administer pethidine analgesia as required. Times to extubation, response to verbal stimulation and orientation, postoperative pain scores and analgesic consumption were recorded. Times to extubation and response to verbal stimulation were significantly longer in the lop group. Pain scores, analgesic consumption and additional analgesic requirements were significantly higher in the Pop group in the first 2 h postoperatively. In conclusion, intra-operative administration of pethidine provided better pain management than postoperative administration

Removal of textile dyes from aqueous solutions by biosorption on mushroom stump wastes

WOS: 000354372400007In this study, the biosorption capacity of Agaricus bisporus/white mushroom stump wastes was evaluated against basic (Basic Red 18), reactive (Levafix Braun E-RN) and acidic (Acid Red 111) dyes. The experiments were carried out with heat-dried and freezing-dried mushroom stump wastes (HDW and FDW). Freezing-dried mushroom stump wastes had laccase activity which showed decolourisation effect for reactive and basic dyes. FDW showed higher reactive dye biosorption capacity compared with HDW. On the other hand, acidic dye biosorption capacity of HDW proved to be considerably higher than that of FDW. Thermodynamic parameters of free energy, enthalpy and entropy obtained from biosorption reactive dye ranging from 293 to 323 K showed that the biosorption experiment was a spontaneous and endothermic process. In this study, the kinetics of the biosorption of reactive dye over mushroom stump wastes was also investigated. The investigation revealed that the process proceeds via pseudo-second-order kinetics. On the whole, this study has demonstrated that mushroom stump wastes are promising biosorbents for the decolourisation of waste water containing different kinds of dyes from textile industry.Ege UniversityEge University [2012/CSUAM/004]The financial support from Ege University under contract 2012/CSUAM/004 is gratefully acknowledged. PE-MA Mushroom Production and Co. is thanked for providing mushroom for this study

Dilution of rocuronium to 0.5 mg/mL with 0.9% NaCl eliminates the pain during intravenous injection in awake patients

In a randomized, double-blinded, controlled study, we evaluated the effect of diluting rocuronium 10 mg/mL to 1 or 0.5 mg/mL with 0.9% NaCl on the pain associated with IV administration of rocuronium with small doses given before succinylcholine or nondepolarizing agent administration. One hundred fifty patients undergoing surgical procedures that required general anesthesia were randomized into three groups. Group 1 received rocuronium 10 mg/mL. Groups 2 and 3 received I and 0.5 mg/mL of rocuronium, respectively. Patient demographics, pain scores, osmolality, and the pH of the solutions were recorded. Group 1 had the most intense and frequent pain response. Eighty percent of patients in this group reported pain on injection. In Group 2, the incidence and intensity of pain were significantly less when compared with those of Group 1. In this group, 38% of patients reported pain during injection. In Group 3, none of the patients experienced pain on injection. The pH values and osmolalities of study solutions were not significantly different among groups. In conclusion, in awake patients, dilution of rocuronium. 10 mg/mL at small doses given before succinylcholine or nondepolarizing agent administration of 0.06 mg/kg to 0.5 mg/mL with 0.9% NaCl is a simple and cost-effective strategy for preventing pain during IV rocuronium injection

Ischemic preconditioning attenuates the lipid peroxidation and remote lung injury in the rat model of unilateral lower limb ischemia reperfusion

Ischemia and reperfusion of the skeletal muscle tissue may cause remote lung injury. We aimed to evaluate the protective effect of ischemic preconditioning (IP) on the lung during unilateral lower limb ischemia reperfusion (IR)

Mutation in \u3ci\u3eATG5\u3c/i\u3e reduces autophagy and leads to ataxia with developmental delay

Autophagy is required for the homeostasis of cellular material and is proposed to be involved in many aspects of health. Defects in the autophagy pathway have been observed in neurodegenerative disorders; however, no genetically-inherited pathogenic mutations in any of the core autophagy-related (ATG) genes have been reported in human patients to date. We identified a homozygous missense mutation, changing a conserved amino acid, in ATG5 in two siblings with congenital ataxia, mental retardation, and developmental delay. The subjects’ cells display a decrease in autophagy flux and defects in conjugation of ATG12 to ATG5. The homologous mutation in yeast demonstrates a 30-50% reduction of induced autophagy. Flies in which Atg5 is substituted with the mutant human ATG5 exhibit severe movement disorder, in contrast to flies expressing the wild-type human protein. Our results demonstrate the critical role of autophagy in preventing neurological diseases and maintaining neuronal health