Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder.

Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome

Inhibitory Effect of Cinnamomum Zeylanicum and Camellia Sinensis Extracts on the Hen Egg-White Lysozyme Fibrillation

Abstract: Background & Aims: Many neurodegenerative diseases including Alzheimer’s, Parkinson and Huntington diseases are associated with the deposition proteinaceous aggregates known as amyloid fibrils. Currently, there is no approved therapeutic agent for inhibition of fibrillar assemblies. One important approach in the development of therapeutic agents is the use of herbal extracts. At the present comparative study, the effect of Cinnamomum zeylanicum Nees and Camellia sinensis L, extracts on prevention of hen egg white lysozyme (HEWL) amyloidogenesis were studied. Methods: In this experimental study, acidic pH and high temperature were used to drive the protein towards amyloid formation. Lysozyme was dissolved at 2 mg/mL in 50mM glycine buffer (pH 2.5), and then incubated at 57 ?C for a specified time while stirred gently by Teflon magnetic bars. Measurement of thioflavin T fluorescence intensity and AFM micrography were used to characterize the HEWL fibrillation processes. Data were analyzed through SPSS 16 using descriptive statistics as well as independent t-test. Results: In the absence of the extracts, soluble oligomers became evident after 24 h of incubation, followed by subsequent appearance of mature fibrils after 48h. Upon incubation with various concentrations of Cinnamomum zeylanicum and Camellia sinensis extracts in range of 0.1-1 mg/ml, formation of fibrillar assemblies were dose-dependently inhibited but the extract of Camellia was more efficient (P=0.025). Also, in contrast to Cinnamomum, Camellia extract can stabilize native protein and reverse partial unfolded form into native form and thus, can inhibit all of amyloid formation pathways. Conclusion: The obtained results suggest that poly phenols of the extracts directly insert into amyloidogenic core of early aggregates and inhibit amyloid fibril formation but Camellia extract, due to its specific chemical structure, is probably more effective for aggregation inhibition. Keywords: Lysozyme, Cinnamomum zeylanicum extract, Camellia sinensis extract, Amyloid aggregation inhibitio

Screening of Bread Wheat Genotypes for Stem Reserves Remobilization, Relative Water Content and Osmotic Adjustment under Drought Stress

Drought one of the most important global threats against bread wheat production. In order to identify physiological traits associated with drought tolerance, 52 bread wheat varieties were cultured under two normal and drought stress condition in a randomized complete block desigen with three replications. RWC (in three independent times), leaf rolling, leaf silvering, days to flowering, days to maturity and stem reserve remobilization were investigeted. Also in a pot experiment osmotic adjustment of the varieties were measured at seedling stage. varieties Star and Bezostaya had the highest RWC (0.79 and 0.78, respectively). Osmotic adjustment in Rasol and Unknown11 were highest (0.58 and 0.56, respectively). Varieties Tipik, Unknown11 and Azar2 showed the least decrease in thousand grain weight after spraying with KI (4.8, 5.5 and 5.5, respectively). Also varieties Dez, Gaspard and MV-17 have the highest degree of leaf silvering and varieties Niknejad, Star and Kohdasht under drought stress were able than the other varieties bring their leaves to form a rolling and cope with water deficit. Under drought stress, Varieties Alborz, Zagros and Inia were observed premature than the other varieties and Gaspard and Kaslojen varieties were observed late mature than the other varieties. Altogetehr varieties Kohdasht, Star and Bezostaya can be used as genetic resources for leaf water retention under drought stress condition for imjproving other varieties. Also as Azar2 and Unknown11 had highest amount of thousand grain weight under normal condition and simoultanously showed high ability in stem reserves remobilization they can be selected as parents in crosses for improving these traits

Evaluation of drought tolerance in corn (Zea mays L.) new hybrids with using stress tolerance indices

In order to study the effect of drought stress on morphophysiologic characteristics,yield and yield components of 8 new hybrids of corn (Zea maize L.) and KSC704commercial hybrid as control resistant to drought and warm (which were bred andscreened in Khozestan province condition), an experiment was conducted in aRandomized Complete Block Design (RCBD) with three replications underdrought stress and normal irrigation at Khorasan-Razavi Agriculture ResearchCenter, Mashhad, Iran on June 10, 2011. The results of analyze variance showedthat under normal irrigation and drought condition, there was a significantdifference (p&lt;0.01) between the hybrids. Mean comparison of hybrids revealedthat in normal irrigation H6 and in drought stress H8 hybrid had the maximumgrain yield (12.85 and 6.75 ton/ha, respectively). Based on the grain yields ofstudied hybrids, stress tolerance index (STI), stress susceptibility index (SSI),tolerance index (TOI), mean productivity (MP), geometric mean productivity(GMP), harmonic mean (HM) and golden mean (GM) were estimated. Resultsshowed that among drought tolerance indices, MP, GMP, STI and HM were thebest indices for corn and KSC704 hybrid and H4 had the highest tolerance todrought in Mashhad weather condition.</jats:p

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ABSTRACT In order to study the effect of drought stress on morphologic traits, yield and yield components of 9 new hybrids of corn (Zea maize L.), an experiment was conducted in a Randomized Complete Block Design (RCBD) with three replications under drought stress and normal irrigation based on 80 and 50 % allowing water depletion, respectively at Khorasan-Razavi Agriculture Research Center, Mashhad, Iran on June 10, 2011. The results of analyze variance showed that under normal irrigation and drought condition, there was a significant difference (p&lt;0.01) between the hybrids. Mean comparison of hybrids revealed that in normal irrigation H6 and in drought stress H8 hybrid had the maximum grain yield (12.85 and 6.75 ton/ha, respectively). Under normal irrigation and water shortage, plant height and kernel no/row had the highest positive phenotypic correlation with kernel yield. In drought condition, grain yield was decreased due to the reduction cumulative effects in yield components.

Effect of intracerebroventricular injection of GABA receptors antagonists on morphine-induced changes in GABA and GLU transmission within the mPFC: An in vivo microdialysis study

Objective(s): Many studies have focused on ventral tegmental area than of other mesocorticolimbic areas, and implicated a key role for the medial prefrontal cortex (mPFC) in the development of addictive behaviors. So far, the role of gamma-aminobutyric acid (GABA) receptors in the discriminative properties of morphine has received little attention and few studies evaluated the role of these receptors in drug dependence. Hence, we investigated the role of this receptor on morphine- induced GABA/ glutamate (GLU) changes in the mPFC following morphine administration using in vivo microdialysis.Materials and Methods: In this study, 60 rats weighing 270-300 g were divided into six groups. First, microdialysis probe was inserted into the mPFC and was perfused with artificial cerebrospinal fluid and collected the baseline samples in all groups. In saline and morphine groups, the saline, in phaclophen and (phaclofen+morphine) groups, phaclofen (100 nmol), and in bicuculline and (bicuculline+morphine) groups, bicuculline (20 nmol) was injected intracerebroventricular. In saline, phaclofen and bicuculline groups 20 min later, animals received saline (0.2 ml, IP) and others groups received morphine (20 mg/kg, IP).Results: Our results showed that morphine increased the average concentration of GABA and decreased the concentration of GLU within mPFC. Pretreatment with phaclofen and bicuculline 20 min before morphine administration had no effect on GABA and GLU release for 100 min.Conclusion: The present study indicated that morphine influence the GABA and GLU transmission in mPFC. Therefore evaluation of neurochemistry changes of this neural circuitry may provide further insight into the mechanisms underlying drug dependence

Thermal aggregation of α-chymotrypsin: Role of hydrophobic and electrostatic interactions

We have recently reported that electrostatic interactions may play a critical role in alcohol-induced aggregation of α-chymotrypsin (CT). In the present study, we have investigated the heat-induced aggregation of this protein. Thermal aggregation of CT obeyed a characteristic pattern, with a clear lag phase followed by a sharp rise in turbidity. Intrinsic and ANS fluorescence studies, together with fluorescence quenching by acrylamide, suggested that the hydrophobic patches are more exposed in the denatured conformation. Typical chaperone-like proteins, including α- and β-caseins and α-crystalline could inhibit thermal aggregation of CT, and their inhibitory effect was nearly pH-independent (within the pH range of 7-9). This was partially counteracted by α-, β- and especially γ-cyclodextrins, suggesting that hydrophobic interactions may play a major role. Loss of thermal aggregation at extreme acidic and basic conditions, combined with changes in net charge/pH profile of aggregation upon chemical modification of lysine residues are taken to support concomitant involvement of electrostatic interactions. © 2007 Elsevier B.V. All rights reserved

Thermally induced changes in the structure and activity of yeast hexokinase B

Yeast hexokinase has been poorly characterized in regard with its stability. In the present study, various spectroscopic techniques were employed to investigate thermal stability of the monomeric form of yeast hexokinase B (YHB). The enzyme underwent a conformational transition with a Tm of about 41.9 °C. The structural transition proved to be significantly reversible below 55 °C and irreversible at higher temperatures. Thermoinactivation studies revealed that enzymatic activity diminished significantly at high temperatures, with greater loss of activity observed above 55 °C. Release of ammonia upon deamidation of YHB obeyed a similar temperature-dependence pattern. Dynamic light scattering and size exclusion-HPLC indicated formation of stable aggregates. Taking various findings on the influence of osmolytes and chaperone-like agents on YHB thermal denaturation together, it is proposed that the purely conformational transition of YHB is reversible, and irreversibility is due to aggregation, as a major cause. Deamidation of a critical Asn or Gln residue(s) may also play an important role. © 2008 Elsevier B.V. All rights reserved