Approximately 1.7 kbp of mitochondrial DNA were sequenced from 29 individuals assignable to 11 Uromastyx species or subspecies and two other agamids. U. ocellata and U. ornata had an insertion between the glutamine and isoleucine tRNA genes, which could be folded into a stable stem‐and‐loop structure, and the insertion for U. ornata additionally retained a sequence similar to the glutamine tRNA gene. This corroborates the role of tandem duplication in reshaping mitochondrial gene arrangements, and supports the idea that the origin of light‐strand replication could be relocated within mitochondrial genomes. Molecular phylogeny from different tree‐building methods consistently placed African and Arabian taxa in mutually monophyletic groups, excluding U. hardwickii inhabiting India and Pakistan. Unlike previous studies based on morphology, U. macfadyeni did not cluster with morphologically similar Arabian taxa, suggesting convergent evolution to be responsible for the morphological similarities. Divergence times estimated among the Uromastyx taxa, together with geological and palaeontological evidence, suggest that the Uromastyx agamids originated from Central Asia during the Eocene and colonized Africa after its connection with Eurasia in the early Miocene. Their radiation may have been facilitated by repeated aridification of North Africa since the middle Miocene, and geological events such as the expansion of the Red Sea and the East African Rift Valley. © 2005 The Linnean Society of London, Biological Journal of the Linnean Society, 2005, 85, 247–260.

Oxidative stress is a common mechanism contributing to the initiation and progression of hepatic damage. Hence there is a great demand for the development of agents with potent antioxidant effect. The aim of the present study is to evaluate the efficacy of Holothuria atra extract (HaE) as an antioxidant against 7,12-dimethylbenz[a]anthracene- (DMBA-) induced hepatorenal dysfunction. Experimental animals were divided into two main groups: protective and curative. Each group was then divided into five subgroups pre- or posttreated either with distilled water (DMBA subgroups) or with HaE (200 mg/kg body weight) for seven and fourteen days. Single oral administration of DMBA (15 mg/kg body weight) to Wistar rats resulted in a significant increase in the serum liver enzymes and kidney function's parameters. DMBA increased level of liver malondialdehyde (MDA), decreased levels of reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) in the liver tissue, and induced liver histopathological alterations. Pre- or posttreatment with HaE orally for 14 days significantly reversed the hepatorenal alterations induced following DMBA administration. In conclusion, HaE exhibits good hepatoprotective, curative, and antioxidant potential against DMBA-induced hepatorenal dysfunction in rats that might be due to decreased free radical generation.

In vitro phase I metabolic reactions & cyano conjugates of masitinib.

No abstract

A complete mitochondrial DNA (mtDNA) sequence was determined for the lizard Calotes versicolor (Reptilia; Agamidae). The 16,670-bp genome with notable shorter genes for some protein-coding and tRNA genes had the same gene content as that found in other vertebrates. However, a novel gene arrangement was found in which the proline tRNA (trnP) gene is located in the light strand instead of its typical heavy-strand position, providing the first known example of gene inversion in vertebrate mtDNAs. A segment of mtDNA encompassing the trnP gene and its flanking genes and the control region was amplified and sequenced for various agamid taxa to investigate timing and mechanism of the gene inversion. The inverted trnP gene organization was shared by all South Asian draconine agamids examined but by none of the other Asian and African agamids. Phylogenetic analyses including clock-free Bayesian analyses for divergence time estimation suggested a single occurrence of the gene inversion on a lineage leading to the draconine agamids during the Paleogene period. This gene inversion could not be explained by the tandem duplication/random loss model for mitochondrial gene rearrangements. Our available sequence data did not provide evidence for remolding of the trnP gene by an anticodon switch in a duplicated tRNA gene. Based on results of sequence comparisons and other circumstantial evidence, we hypothesize that inversion of the trnP gene was originally mediated by a homologous DNA recombination and that the de novo gene organization that does not disrupt expression of mitochondrial genes has been maintained in draconine mtDNAs for such a long period of time.

This study involved the identification and characterization of ponatinib by LC-MS/MS. Additionally ponatinib reactive metabolites were also investigated using KCN as a trapping agent, showing the formation of four reactive cyano adducts.

A highly sensitive and simple spectrofluorimetric method has been developed and validated for the determination of the antidepressant fluvoxamine (FXM) in its dosage forms and plasma. The method was based on nucleophilic substitution reaction of FXM with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole in an alkaline medium (pH 8) to form a highly fluorescent derivative that was measured at 535 nm after excitation at 470 nm. The factors affecting the reaction was carefully studied and optimized. The kinetics of the reaction was investigated, and the reaction mechanism was presented. Under the optimized conditions, linear relationship with good correlation coefficient (0.9995) was found between the fluorescence intensity and FXM concentration in the range of 65-800 ng ml(-1). The limits of detection and quantitation for the method were 21 and 64 ng ml(-1), respectively. The precision of the method was satisfactory; the values of relative standard deviations did not exceed 2.17%. The proposed method was successfully applied to the determination of FXM in its pharmaceutical tablets with good accuracy; the recovery values were 97.8-101.4 +/- 1.08-2.75%. The results obtained by the proposed method were comparable with those obtained by the official method. The high sensitivity of the method allowed its successful application to the analysis of FXM in spiked human plasma. The proposed method is superior to the previously reported spectrofluorimetric method for determination of FXM in terms of its simplicity. The proposed method is practical and valuable for its routine application in quality control and clinical laboratories for analysis of FXM.

Using LC-MS/MS, six phase I foretinib metabolites in addition to four potential reactive metabolites, two aldehydes and two iminium ions, were detected and the bioactivation pathways were proposed.