Brain Insulin Dysregulation: Implication for Neurological and Neuropsychiatric Disorders

Arduous efforts have been made in the last three decades to elucidate the role of insulin in the brain. A growing number of evidences show that insulin is involved in several physiological function of the brain such as food intake and weight control, reproduction, learning and memory, neuromodulation and neuroprotection. In addition, it is now clear that insulin and insulin disturbances particularly diabetes mellitus may contribute or in some cases play the main role in development and progression of neurodegenerative and neuropsychiatric disorders. Focusing on the molecular mechanisms, this review summarizes the recent findings on the involvement of insulin dysfunction in neurological disorders like Alzheimer’s disease, Parkinson’s disease and Huntington’s disease and also mental disorders like depression and psychosis sharing features of neuroinflammation and neurodegeneration.     

Determination of metformin in human plasma by high-performance liquid chromatography

A simple, selective and sensitive high-performance liquid chromatographic method with spectrophotometric detection was developed for the determination of antihyperglycemic agent metformin in human plasma using a novel sample extraction procedure. Liquid-liquid extraction of metformin and ranitidine (as internal standard) from plasma samples was performed with 1-butanol/n-hexane (50:50, v/v) in alkaline condition followed by back-extraction into diluted acetic acid. Chromatography was carried out using a silica column (250 mmx4.6 mm, 5 microm) under isocratic elution with acetonitrile-40 mM aqueous sodium dihydrogen phosphate (25:75, v/v), pH 6. The limit of quantification (LOQ) was 15.6 ng/ml and the calibration curves were linear up to 2000 ng/ml. The mean absolute recoveries for metformin and internal standard using the present extraction procedure were 98 and 95%, respectively. The intra- and inter-day coefficient of variation and percent error values of the assay method were all less than 8.3%.     

Orexinergic Neurotransmission in Temperature Responses to Methamphetamine and Stress: Mathematical Modeling as a Data Assimilation Approach

Experimental Data

Orexinergic neurotransmission is involved in mediating temperature responses to methamphetamine (Meth). In experiments in rats, SB-334867 (SB), an antagonist of orexin receptors (OX1R), at a dose of 10 mg/kg decreases late temperature responses (t>60 min) to an intermediate dose of Meth (5 mg/kg). A higher dose of SB (30 mg/kg) attenuates temperature responses to low dose (1 mg/kg) of Meth and to stress. In contrast, it significantly exaggerates early responses (t<60 min) to intermediate and high doses (5 and 10 mg/kg) of Meth. As pretreatment with SB also inhibits temperature response to the stress of injection, traditional statistical analysis of temperature responses is difficult.

Mathematical Modeling

We have developed a mathematical model that explains the complexity of temperature responses to Meth as the interplay between excitatory and inhibitory nodes. We have extended the developed model to include the stress of manipulations and the effects of SB. Stress is synergistic with Meth on the action on excitatory node. Orexin receptors mediate an activation of on both excitatory and inhibitory nodes by low doses of Meth, but not on the node activated by high doses (HD). Exaggeration of early responses to high doses of Meth involves disinhibition: low dose of SB decreases tonic inhibition of HD and lowers the activation threshold, while the higher dose suppresses the inhibitory component. Using a modeling approach to data assimilation appears efficient in separating individual components of complex response with statistical analysis unachievable by traditional data processing methods.     

Karyological studies of Iranian <Emphasis Type="Italic">Allium</Emphasis> L. (Amaryllidaceae) species with focus on sect. <Emphasis Type="Italic">Acanthoprason</Emphasis>. 1. Mitotic chromosomes

Eighteen species and subspecies (34 accessions) of Allium sect. Acanthoprason and 11 species (17 accessions) belonging to other subgenera and sections of Allium were karyologically investigated and include first reports for 12 species. The examined plants of 47 accessions were diploid, three accessions of two species were tetraploid, and in the A. bisotunense accession, we found a mix of di- and triploid individuals. B chromosomes were found in 10 accessions. A basic chromosome number of x = 8 was confirmed for all investigated members of subg. Melanocrommyum and subg. Allium, and x = 9 for Allium tripedale of subg. Nectaroscordum. Idiograms were drawn for each accession, and metaphase images are presented illustrating observed chromosomal variations. Also, karyotype features and asymmetry parameters were calculated for all accessions. Chromosomal aberrations, e.g. aneuploid cells or loss of whole or parts of chromosome arms, were rarely observed. In general, the karyotypes showed low variation in inter- and intrachromosomal asymmetry especially inside of the taxonomic groups, though satellited chromosomes were good markers for subgenera and even specific for two studied sections of subg. Allium. Six different types of satellites were recognized, two of them were newly described: Type P was prevalent in subg. Melanocrommyum, and type O in sect. Codonoprasum. Statistical analyses were performed on five karyological parameters to test correct relationships and also to test previous grouping hypotheses. Although our data confirm distinct karyological characters for the subgenera investigated, the remarkable morphological diversity inside of subg. Melanocrommyum is not mirrored by striking karyological differences.     

A cyclodextrin host-guest recognition approach to an electrochemical sensor for simultaneous quantification of serotonin and dopamine

An electrochemical sensor for simultaneous quantification of serotonin (5-hydroxytryptamine, 5-HT) and dopamine (DA) using a β-cyclodextrin/poly(N-acetylaniline)/carbon nanotube composite modified carbon paste electrode has been developed. Synergistic effect of multi-walled carbon nanotube (MWCNT) in addition to the pre-concentrating effect of β-cyclodextrin (β-CD) as well as its different inclusion complex stability with 5-HT and DA was used to construct an electrochemical sensor for quantification of these important neurotransmitters. The overlapping anodic peaks of 5-HT and DA at 428 mV on bare electrode resolved in two well-defined voltammetric peaks at 202 and 363 mV vs. Ag/AgCl respectively. The oxidation mechanism of 5-HT and DA on the surface of the electrode was investigated by cyclic voltammetry and it was found that the electrode processes are pH dependent and electrochemical oxidation of 5-HT is totally irreversible while the electrode gave a more reversible process to DA. Under optimized conditions, linear calibration curves were obtained in the range of about 4-200 μM with a detection limits down to sub-μM levels (S/N=3) after 20-s accumulation, for both. The proposed sensor was shown to be remarkably selective for 5-HT and DA in matrices containing different species including ascorbic acid and uric acid. The suitability of the developed method was tested for the determination of 5-HT and DA in the Randox Synthetic Plasma samples and acceptable recoveries were obtained for a set of spiked samples.     

<Emphasis Type="Italic">Aureobasidium mangrovei</Emphasis> sp. nov., an ascomycetous species recovered from Hara protected forests in the Persian Gulf,Iran

A new ascomycetous black yeast-like species was recovered from healthy plant (Avicennia marina) of Hara protected mangrove forests at Qeshm Island, Iran. Morphological, physiological analysis as well as a molecular analysis of the internal transcribed spacer (ITS) and partial large ribosomal subunit (D1/D2 domains) confirmed the placement of this strain in the genus Aureobasidium and based on considerable sequence divergence, distinguishable cardinal growth temperatures and salt tolerance a new species Aureobasidium mangrovei sp. nov. is proposed. However, the type strain micro-morphologically is not clearly distinguishable from other members of the genus. The type strain, Aureobasidium mangrovei was preserved in a metabolically inactive state at the Iranian Biological Resource Centre, Tehran, Iran as IBRC-M 30265^T and the ex-type culture is deposited in the CBS yeast collection of the Westerdijk Fungal Biodiversity Institute, Utrecht, The Netherlands as CBS 142205^T. The GenBank accession numbers for the nucleotide sequences of the large subunit ribosomal DNA and ITS region are KY089084 and KY089085, respectively. The MycoBank number of the new species is MB 823444.     

Biotransformation of methyl tert-butyl ether by human cytochrome P450 2A6

Methyl tert-butyl ether (MTBE) is widely used as gasoline oxygenate and octane number enhancer for more complete combustion in order to reduce the air pollution caused by motor vehicle exhaust. The possible adverse effects of MTBE on human health are of major public concern. However, information on the metabolism of MTBE in human tissues is scarce. The present study demonstrates that human cytochrome P450 2A6 is able to metabolize MTBE to tert-butyl alcohol (TBA), a major circulating metabolite and marker for exposure to MTBE. As CYP2A6 is known to be constitutively expressed in human livers, we infer that it may play a significant role in metabolism of gasoline ethers in liver tissue.