Small-scale chemistry for a hands-on approach to chemistry practical work in secondary schools: Experiences from Ethiopia

The purpose of this study was to investigate the possibility of using a small-scale chemistry (SSC) approach as a means of performing chemistry practical activities in Ethiopian secondary schools. A total of eight  experiments from two topics, electrolysis and rate of reaction, in the  Ethiopian grade 11 chemistry syllabus were modified into SSC for use with the MyLab Chemistry Kits (Northwest University, South Africa). The  evaluation involved classroom testing of the SSC materials to investigate the effect of the approach compared to the regular teaching approach. Two comparable groups of Grade 11 science stream students (188 experimental; 195 control) and their chemistry teachers participated in the study. Triangulation procedures involving classroom observation of the use of the SSC approach in classrooms, student achievement tests (pre and post-test), questionnaires, and interviews were employed for data  collection. Results showed that the SSC approach can increase students understanding of chemistry concepts. Furthermore, despite the presence of some challenges in operating the smallscale equipment, collecting  quantitative data, and maintaining class discipline, the SSC approach was viewed by both teachers and students as cost and time saving, safer, easy to use and enjoyable. [AJCE 4(3), Special Issue, May 2014

Resolution of the clinical features of tyrosinemia following orthotopic liver transplantation for hepatoma

The clinical history before transplantation and subsequent clinical and biochemical course of 3 children and one adult with hereditary tyrosinemia treated by orthotopic hepatic transplantation is described. All four patients are now free of their previous dietary restrictions and appear to be cured of both their metabolic disease and their hepatic neoplasm. © 1986 Elsevier Science Publishers B.V. All rights reserved

Guidelines for diagnosis and management of the cobalamin-related remethylation disorders cblC, cblD, cblE, cblF, cblG, cblJ and MTHFR deficiency

BACKGROUND: Remethylation defects are rare inherited disorders in which impaired remethylation of homocysteine to methionine leads to accumulation of homocysteine and perturbation of numerous methylation reactions. OBJECTIVE: To summarise clinical and biochemical characteristics of these severe disorders and to provide guidelines on diagnosis and management. DATA SOURCES: Review, evaluation and discussion of the medical literature (Medline, Cochrane databases) by a panel of experts on these rare diseases following the GRADE approach. KEY RECOMMENDATIONS: We strongly recommend measuring plasma total homocysteine in any patient presenting with the combination of neurological and/or visual and/or haematological symptoms, subacute spinal cord degeneration, atypical haemolytic uraemic syndrome or unexplained vascular thrombosis. We strongly recommend to initiate treatment with parenteral hydroxocobalamin without delay in any suspected remethylation disorder; it significantly improves survival and incidence of severe complications. We strongly recommend betaine treatment in individuals with MTHFR deficiency; it improves the outcome and prevents disease when given early

Slow-onset inhibition of fumarylacetoacetate hydrolase by phosphinate mimics of the tetrahedral intermediate: kinetics, crystal structure and pharmacokinetics

FAH (fumarylacetoacetate hydrolase) catalyses the final step of tyrosine catabolism to produce fumarate and acetoacetate. HT1 (hereditary tyrosinaemia type 1) results from deficiency of this enzyme. Previously, we prepared a partial mimic of the putative tetrahedral intermediate in the reaction catalysed by FAH co-crystallized with the enzyme to reveal details of the mechanism [Bateman, Bhanumoorthy, Witte, McClard, Grompe and Timm (2001) J. Biol. Chem. 276, 15284–15291]. We have now successfully synthesized complete mimics CEHPOBA {4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate} and COPHPAA {3-[(3-carboxy-2-oxopropyl)hydroxyphosphinyl]acrylate}, which inhibit FAH in slow-onset tight-binding mode with K(i) values of 41 and 12 nM respectively. A high-resolution (1.35 Å; 1 Å=0.1 nm) crystal structure of the FAH·CEHPOBA complex was solved to reveal the affinity determinants for these compounds and to provide further insight into the mechanism of FAH catalysis. These compounds are active in vivo, and CEHPOBA demonstrated a notable dose-dependent increase in SA (succinylacetone; a metabolite seen in patients with HT1) in mouse serum after repeated injections, and, following a single injection (1 μmol/g; intraperitoneal), only a modest regain of FAH enzyme activity was detected in liver protein isolates after 24 h. These potent inhibitors provide a means to chemically phenocopy the metabolic defects of either HT1 or FAH knockout mice and promise future pharmacological utility for hepatocyte transplantation