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Myo
Selected AbstractsA review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders,focus on magnetic resonance spectroscopy (MRS) studiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005Hyeonjin Kim Abstract Myo -inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo -inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo -inositol and the PI-cycle. It relates this to the current in vivo evidence for myo -inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo -inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder. Copyright © 2005 John Wiley & Sons, Ltd. [source] Oscillatory transverse electric field enhances protein resolution and capacity of size-exclusion chromatographyJOURNAL OF SEPARATION SCIENCE, JSS, Issue 5 2006Guo-Min Tan Abstract Protein separations by a novel size-exclusion electrochromatography (SEEC) are presented. The present SEEC, denoted as pSEEC, was established with an oscillatory low-voltage electric field perpendicular to the mobile-phase streamline. Retention experiments with different proteins indicated that the influence of electric field strength on the partition coefficient is different for different proteins as well as for the same protein under different mobile-phase conditions. These results of protein retention led to the experimental design of protein separations with binary mixtures of BSA and immunoglobulin G (IgG), myoglobin (Myo) and lysozyme (Lys), as well as ovalbumin (Oval) and Myo. The separation results for the binary protein systems sufficiently exhibited the applicability of the pSEEC for various separations in terms of their molecular weights (MWs) as well as pIs. For example, it was possible to separate the gel-excluded proteins (BSA/IgG) as well as gel-permeable and similar-molecular-weight proteins (Myo/Lys) by the pSEEC. Moreover, in the cases of Oval/Myo, which could be partially separated by size-exclusion chromatography, the use of the pSEEC greatly improved the resolution and the separation became possible at high sample loading. The results indicate that the pSEEC technology is promising for preparative protein separations. [source] Effects of graded levels of dietary myo -inositol on non-specific immune and specific immune parameters in juvenile Jian carp (Cyprinus carpio var. Jian)AQUACULTURE RESEARCH, Issue 10 2010Wei-Dan Jiang Abstract The aim of this study was to evaluate the effects of myo -inositol (MI) on non-specific immune and specific immune defence in fish. A total of 1050 Jian carp (Cyprinus carpio var. Jian) (22.28±0.07 g) were randomly distributed into seven groups, of three replicates each, of feeding diets containing graded levels of MI (163.5, 232.7, 384.2, 535.8, 687.3, 838.8 and 990.3 mg MI kg,1 diet). After a 60-day growth trial, an infectious trial was conducted by injection of Aeromonas hydrophila for 17 days. Results showed that the red blood cell (RBC) and the white blood cell count were significantly increased with increasing MI levels up to 535.8 mg kg,1 diet (P<0.05). The spleen index showed a tendency similar to RBC, whereas the head kidney index showed the inverse pattern (P<0.05). The phagocytic activity of leucocytes, haemagglutination titre, lysozyme activity, anti- A. hydrophila antibody titre and immunoglobulin M, after being injected with A. hydrophila, were all improved with an increase in the MI levels up to 232.7,687.3 mg kg,1 diet respectively (P<0.05). Myo -inositol did not influence serum acid phosphatase activity and total iron-binding capacity (P>0.05). These results suggested that MI could enhance non-specific immune and specific immune responses in fish. [source] Myo -inositol prevents oxidative damage, inhibits oxygen radical generation and increases antioxidant enzyme activities of juvenile Jian carp (Cyprinus carpio var. Jian)AQUACULTURE RESEARCH, Issue 15 2009Wei-Dan Jiang Abstract This study was conducted to evaluate the effects of dietary myo -inositol (MI) on the antioxidant status of juvenile Jian carp (Cyprinus carpio var. Jian). A total of 1050 Jian carp (22.28±0.07 g) were randomly distributed into seven groups of three replicates each, feeding diets containing graded levels of MI (163.5, 232.7, 384.2, 535.8, 687.3, 838.8 and 990.3 mg kg,1 diet) for 60 days. Results indicated that the malondialdehyde content was the lowest for fish fed diets containing ,384.2 mg MI kg,1, and the highest for fish fed the MI-unsupplemented basal diet (P<0.05). The protein carbonyl content was decreased with increasing dietary MI levels up to 535.8 mg kg,1 diet, and no differences were found with a further increase in the MI concentration. The anti-superoxide anion capacity (ASA) and anti-hydroxyl radical capacity (AHR) were increased with increasing MI levels up to 535.8 mg kg,1 diet, and plateaued thereafter. The superoxide dismutase and glutathione- S -transferase activities showed the same tendency with the ASA capacity. Catalase, glutathione peroxidase and glutathione reducase activities were improved with increasing MI levels up to 838.8, 384.2 and 687.3 mg kg,1 diet, respectively, and remained nearly constant thereafter. These results suggested that MI could inhibit oxygen radical generation, increase enzymatic antioxidant capacity and prevent oxidative damage of carp. Dietary MI requirements for ASA and AHR activities of juvenile Jian carp were 567.94 and 517.22 mg MI kg,1 diet respectively. [source] Study of a myo -inositol hexaphosphate-based cream to prevent dystrophic calcinosis cutisBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2005F. Grases Summary Background, Calcinosis cutis is a disorder caused by abnormal deposits of calcium phosphate in the skin and is observed in diverse disorders. Myo -inositol hexaphosphate (InsP6) is a diet-dependent molecule found in all mammalian fluids and tissues, which exhibits an extraordinary capacity as a crystallization inhibitor of calcium salts. Objectives, To establish the effects of topically administered InsP6 cream on artificially provoked dystrophic calcifications in soft tissues. Methods, Fourteen male Wistar rats were randomly assigned into two groups: control and treated groups. Rats were fed with an InsP6 -free or phytate diet. Plaque formation was induced by subcutaneous injection of 0·1% KMnO4 solution. From 4 days before plaque induction to the end of the experiment, control rats were treated topically with a standard cream, whereas treated rats were treated with the same cream with 2% InsP6 or phytate (as sodium salt). Calcification of plaques was allowed to proceed for 10 days. InsP6 in urine was determined. The plaques were excised and weighed. Results, It was found that when InsP6 was administered topically through a moisturizing cream (2% InsP6 -rich), the plaque size and weight were notably and significantly reduced compared with the control group (1·6 ± 1·1 mg InsP6 -treated, 26·7 ± 3·0 mg control). The InsP6 urinary levels for animals treated with the InsP6 -enriched cream were considerably and significantly higher than those found in animals treated topically with the cream without InsP6 (16·96 ± 4·32 mg L,1 InsP6 -treated, 0·06 ± 0·03 mg L,1 control). Conclusions, This demonstrates the important capacity of InsP6 as a crystallization inhibitor and also demonstrates that it is possible to propose topical use as a new InsP6 administration route. [source] The role of taurine in diabetes and the development of diabetic complicationsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2001Svend Hřime Hansen Abstract The ubiquitously found ,-amino acid taurine has several physiological functions, e.g. in bile acid formation, as an osmolyte by cell volume regulation, in the heart, in the retina, in the formation of N -chlorotaurine by reaction with hypochlorous acid in leucocytes, and possibly for intracellular scavenging of carbonyl groups. Some animals, such as the cat and the C57BL/6 mouse, have disturbances in taurine homeostasis. The C57BL/6 mouse strain is widely used in diabetic and atherosclerotic animal models. In diabetes, the high extracellular levels of glucose disturb the cellular osmoregulation and sorbitol is formed intracellularly due to the intracellular polyol pathway, which is suspected to be one of the key processes in the development of diabetic late complications and associated cellular dysfunctions. Intracellular accumulation of sorbitol is most likely to cause depletion of other intracellular compounds including osmolytes such as myo -inositol and taurine. When considering the clinical complications in diabetes, several links can be established between altered taurine metabolism and the development of cellular dysfunctions in diabetes which cause the clinical complications observed in diabetes, e.g. retinopathy, neuropathy, nephropathy, cardiomyopathy, platelet aggregation, endothelial dysfunction and atherosclerosis. Possible therapeutic perspectives could be a supplementation with taurine and other osmolytes and low-molecular compounds, perhaps in a combinational therapy with aldose reductase inhibitors. Copyright © 2001 John Wiley & Sons, Ltd. [source] Sorbitol and myo -inositol levels and morphology of sural nerve in relation to peripheral nerve function and clinical neuropathy in men with diabetic, impaired, and normal glucose toleranceDIABETIC MEDICINE, Issue 4 2000G. Sundkvist Abstracts Aims Sorbitol and myo -inositol levels and morphology of sural nerve were compared with nerve function and clinical neuropathy in men with diabetic, impaired (IGT), and normal glucose tolerance. Methods After neurography of sural nerve and determinations of sensory thresholds for vibration, warm and cold on the foot, whole nerve sural nerve biopsy was performed in 10 men with Type 1 diabetes mellitus, 10 with IGT, and 10 with normal glucose tolerance. Polyol levels were assessed by gas,liquid chromatography/mass spectrometry. Results Sural nerve amplitudes were significantly lower and sorbitol levels significantly higher in diabetic patients (median (interquartile range)) (3.7 (3.5) ,V and 643 (412) pmol/mg protein, respectively) both compared with IGT (11.3 (10.6) ,V; P = 0.04 and 286 (83) pmol/mg protein; P = 0.0032, respectively) and normally glucose tolerant (10.0 (11.6); P = 0.0142 and 296 (250) pmol/mg protein; P = 0.0191, respectively) subjects. There were no differences in nerve morphology between the three groups. Nerve myo -inositol levels correlated, however, positively with cluster density (rs = 0.56; P = 0.0054). In diabetic and IGT subjects, sural nerve amplitudes (2.6 (3.8) vs. 12.1 (10.6) ,V; P = 0.0246) and myelinated nerve fibre density (MNFD; 4076 (1091) vs. 5219 (668) nerve fibres/mm2; P = 0.0021) were significantly lower in nine subjects with clinical neuropathy than in 10 without. Conclusions Nerve degeneration (i.e. MNFD) correlated with clinical neuropathy but not with glucose tolerance status whereas nerve myo -inositol levels positively correlated with signs of nerve regeneration (i.e. increased cluster density). [source] Resistance of apple trees to Cydia pomonella egg-laying due to leaf surface metabolitesENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2008Nadia Lombarkia Abstract During host plant selection and particularly after alighting on a plant, chemical cues from the plant surface influence an insect's acceptance of the plant and, subsequently, its egg-laying behaviour. Primary metabolites in the phylloplane may be more important than hitherto known. We have shown that soluble carbohydrates, such as glucose, fructose, and sucrose, and sugar alcohols, such as sorbitol, quebrachitol, and myo -inositol, can be detected by insects after contacting the plant and that they positively influence egg-laying of the codling moth, Cydia pomonella (L.) (Lepidoptera: Tortricidae), on apple trees. We addressed the question whether a lack of these substances could also explain apple tree resistance to C. pomonella in terms of reduced egg-laying. Leaf surface washings were collected in an apple orchard by spraying water on the resistant cultivar X65-11 and on the susceptible cultivar P5R50A4. The washings were tested on a nylon cloth on isolated females under no-choice conditions. The washings were analysed and synthetic blends, each consisting of the six metabolites in the proportions established in the leaf surface washings of both cultivars, were then tested for their effect on egg-laying of C. pomonella. Dose,response egg-laying tests were carried out on substrates impregnated with the X65-11 leaf surface blend at 1, 100, 1 000, and 10 000 times the natural dose. Egg-laying behaviour in the bioassays with leaf surface washings of both cultivars closely resembled egg-laying in the orchard. Washings of P5R50A4 stimulated egg-laying to a greater extent than those of X65-11 and the water control. Synthetic blends reduced substrate acceptance and egg-laying, compared to the washings of X65-11. Ratios between components within the blend are responsible for this resistance. In conclusion, quantities and ratios of the six primary metabolites found on the leaf surface may influence host preference of C. pomonella as well as their egg-laying behaviour, thus they may play a role in the trees' resistance to the codling moth. [source] Compatible solutes of organisms that live in hot saline environmentsENVIRONMENTAL MICROBIOLOGY, Issue 9 2002Helena Santos Summary The accumulation of organic solutes is a prerequisite for osmotic adjustment of all microorganisms. Thermophilic and hyperthermophilic organisms generally accumulate very unusual compatible solutes namely, di- myo -inositol-phosphate, di-mannosyl-di- myo -inositol-phosphate, di-glycerol-phosphate, mannosylglycerate and mannosylglyceramide, which have not been identified in bacteria or archaea that grow at low and moderate temperatures. There is also a growing awareness that some of these compatible solutes may have a role in the protection of cell components against thermal denaturation. Mannosylglycerate and di-glycerol-phosphate have been shown to protect enzymes and proteins from thermal denaturation in vitro as well, or better, than compatible solutes from mesophiles. The pathways leading to the synthesis of some of these compatible solutes from thermophiles and hyperthermophiles have been elucidated. However, large numbers of questions remain unanswered. Fundamental and applied interest in compatible solutes and osmotic adjustment in these organisms, drives research that, will, in the near future, allow us to understand the role of compatible solutes in osmotic protection and thermoprotection of some of the most fascinating organisms known on Earth. [source] Competition between Non-Classical Single and Double Epimerizations in Cyclitol ChemistryEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 9 2004Ralf Miethchen Abstract Two competitive regio- and stereoselective epimerization reactions were investigated in four cyclitols characterized by four contiguous OH groups with a cis - trans - trans sequence and by varied substituents (OMe, OBz, F, H) adjacent to this tetrol unit. The starting materials were synthesized from L -quebrachitol (compounds 5,7) and myo -inositol (compound 8). Their acetalization with the chloral/DCC reagent system gave cyclic acetals with one epimerized chiral ring atom and also with two epimerized chiral centres. The single epimerization takes place exclusively at the middle C-atom of the cis - trans triol unit in the tetrol sequence (products 15, 17, 19/20 and 24,27), whereas the double epimerization occurs at both of the "centrally located" C-atoms in the cis - trans - trans tetrol unit (products 16, 18, 21 and 28). The product ratios of singly to doubly inverted compounds change as follows: the lower the electron-withdrawing effect of the substituents adjacent to the tetrol unit, the higher the percentage of the corresponding doubly inverted product. However, the singly inverted products remain the major products in all cases. X-ray analyses are given for the starting material 1-fluoro-2- O -(methyl)cyclohexane-2,3,4,5,6-pentol (5) and for the products 1- O -cyclohexylcarbamoyl-2,3- O -(2,2,2-trichloroethylidene)5- O -(methyl)cyclohexane-1,2,3,4,5-pentol (17), 3- O -acetyl-1- O -benzoyl-6- O -cyclohexylcarbamoyl-2- O -methyl-4,5- O -(2,2,2-trichloroethylidene)- muco -inositol (22) and 2,3-di- O -ethylidene)-(+/-)- chiro -inositol (24). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] Stereoselective Synthesis of myo -, neo -, L - chiro, D - chiro, allo -, scyllo -, and epi -Inositol Systems via Conduritols Prepared from p -BenzoquinoneEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2003Michael Podeschwa Abstract A practical route is described for the flexible preparation of a wide variety of inositol stereoisomers and their polyphosphates. The potential of this approach is demonstrated by the synthesis of myo -, L - chiro -, D - chiro -, epi -, scyllo -, allo -, and neo -inositol systems. Optically pure compounds in either enantiomeric form can be prepared from p -benzoquinone via enzymatic resolution of a derived conduritol B key intermediate. High-performance anion-exchange chromatography with pulsed amperometric detection permits inositol stereoisomers to be resolved and detected with high sensitivity. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Rapid decomposition of phytate applied to a calcareous soil demonstrated by a solution 31P NMR studyEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 4 2010A. L. Doolette myo -Inositol hexakisphosphate (phytate) is widely regarded as an abundant form of soil organic phosphorus (P) in many soils. Its abundance is believed to be because of its resistance to microbial degradation. We examined the fate of phytate added to a calcareous soil as a solution at a concentration of 58 mg P kg,1, with and without the addition of wheat straw. The soil was incubated for 13 weeks, with phytate concentrations determined at 0, 1, 4, 7 and 13 weeks using NaOH-EDTA soil extraction followed by 31P nuclear magnetic resonance (NMR) spectroscopy. The phytate concentration declined rapidly, with 18% (phytate + wheat straw) and 12% (phytate) of the initial phytate remaining after 13 weeks. This coincided with an increase in the proportion of orthophosphate relative to total NaOH-EDTA extractable P (from 65 to 81%) and a small increase in , - and , -glycerophosphate concentration, providing evidence for the microbial degradation of phytate. The decrease in phytate concentration was consistent with a first-order decay with a half-life for phytate of 4,5 weeks. This study demonstrates that in the calcareous soil examined, phytate was not highly stable, but a potentially biologically available form of P. In order to quantify the concentration of P species, we developed an improved method of spectral deconvolution. This method accounted for a broad signal (3.5,6.5 ppm) in the monoester region of the spectra that represented up to 23% of the total extractable P. We found that when this broad signal was not included, phytate concentrations were over-estimated by up to 54%. [source] Organic phosphorus speciation and pedogenesis: analysis by solution 31P nuclear magnetic resonance spectroscopyEUROPEAN JOURNAL OF SOIL SCIENCE, Issue 6 2007R. W. McDowell Summary Changes in phosphorus (P) during soil development are central to the understanding of labile P for plant productivity and soil P management. We used NaOH-EDTA extraction with 31P nuclear magnetic resonance spectroscopy (31P NMR), sequential P fractionation, and general soil chemical characterization to better our understanding of P dynamics within two chronosequences (Manawatu and Reefton) and one Basalt maturity sequence under original native vegetation. With time, orthophosphate and orthophosphate monoesters tended to increase with organic C to a maximum of about two-thirds of NaOH-EDTA-extractable P in young soils (16 000 years in the Reefton chronosequence), but gradually declined thereafter to about one-third of NaOH-EDTA-extractable P in the oldest soils (130 000 years old). This coincided with a depletion of P from primary minerals (e.g. apatite) and readily available P for plant production. This depletion of inorganic P resulted in a greater reliance on organic P cycling via mineralization, hence the depletion of the normally recalcitrant monoester-P pool. Concomitantly, the build-up of labile P species (diesters and pyrophosphate) and scyllo - over myo -inositol hexakisphosphate occurred as soils developed, and might be attributed to microbial activity, including scavenging for P. This work highlights the importance of organic P cycling during pedogenesis. [source] Characterization of the myo -inositol transport system in Trypanosoma cruziFEBS JOURNAL, Issue 9 2000Marcelo Einicker-Lamas myo -Inositol is a growth factor for mammalian cells as well as for the pathogenic protozoa Trypanosoma cruzi. Most of the cell surface molecules in this organism rely on myo -inositol as the biosynthetic precursor for phosphoinositides and glycosylated phosphatidylinositols. The aim of this work was to investigate the process of myo -inositol translocation across the parasite cell membrane. myo -Inositol uptake was concentration-dependent in the concentration range 0.1,10 µm with maximal transport obtained at 8 µm. Using sodium-free buffers, where Na+ was replaced by choline or K+, myo -inositol uptake was inhibited by 50%. Furosemide, an inhibitor of the ouabain-insensitive Na+ -ATPase, inhibited the Na+ -dependent and Na+ -independent myo -inositol uptake by 68 and 33%, respectively. In contrast, ouabain, an (Na++/K+) ATPase inhibitor, did not affect transport. Part of the myo -inositol uptake is mediated by active transport as it was inhibited when energy metabolism inhibitors such as carbonyl cyanide p -(trifluoromethoxy)-phenylhydrazone (34%), 2,4-dinitrophenol (50%), KCN (71%) and NaN3 (69%) were added to the medium, or the temperature of the medium was lowered to 4 °C. The addition of glucose (5,50 mm) or mannose (10 mm) did not change the myo -inositol uptake, whereas the addition of 10 mm nonlabeled myo -inositol totally inhibited this transport, indicating that the transporter is specific for myo -inositol. Phloretin (0.3 mm) and phoridzin (5 mm), but not cytochalasin B, were efficient inhibitors of myo -inositol uptake. A portion of the accumulated myo -inositol is converted to inositol phosphates and phosphoinositides. These data show that myo -inositol transport in T. cruzi epimastigotes is mediated by at least two specific transporters , one Na+ -dependent and the other Na+ -independent. [source] A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders,focus on magnetic resonance spectroscopy (MRS) studiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005Hyeonjin Kim Abstract Myo -inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo -inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo -inositol and the PI-cycle. It relates this to the current in vivo evidence for myo -inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo -inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder. Copyright © 2005 John Wiley & Sons, Ltd. [source] Shedding of microparticles by myofibroblasts as mediator of cellular cross-talk during normal wound healingJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2010Véronique J. Moulin Interactions between cells are a crucial mechanism to correctly heal a wounded tissue. Myofibroblasts have a central role during healing but their means to communicate with other cells is unknown. Microparticles (MP) have demonstrated a potential role as mediators of cellular interactions during various diseases. We have analyzed the production of MP by normal (Wmyo) and pathological (hypertrophic scar, Hmyo) myofibroblasts and human dermal fibroblasts (Fb) when treated with serum or plasma as examples of body fluids. We have shown that the presence of these body fluids induced a very significant increase in MP production by Wmyo while no MP production was denoted for Hmyo and Fb. These effects were at least due to thermally sensitive protein(s) with a molecular mass >30,kDa. Furthermore, the increase in MP production was not linked to an increase in apoptotic Wmyo. MP characterization showed that VEGF and FGF2 were present in MP and that endothelial and (myo)fibroblast cell growth can be stimulated by MP treatment. We postulated that MP production by myofibroblasts could modulate mesenchymal cell growth and angiogenesis during normal healing. J. Cell. Physiol. 225: 734,740, 2010. © 2010 Wiley-Liss, Inc. [source] Changing the pathogenetic roadmap of liver fibrosis?JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 7pt1 2008Where did it start; where will it go? Abstract The pathophysiology of liver injury has attracted the interest of experimentalists and clinicians over many centuries. With the discovery of liver-specific pericytes , formerly called fat-storing cells, Ito-cells, lipocytes, and currently designated as hepatic stellate cells (HSC) , the insight into the cellular and molecular pathobiology of liver fibrosis has evolved and the pivotal role of HSC as a precursor cell-type for extracellular matrix,producing myofibroblasts has been established. Although activation and transdifferentiation of HSC to myofibroblasts is still regarded as the pathogenetic key mechanism of fibrogenesis, recent studies point to a prominent heterogeneity of the origin of myofibroblasts. Currently, the generation of matrix-synthesizing fibroblasts by epithelial,mesenchymal transition, by influx of bone marrow,derived fibrocytes into damaged liver tissue, and by differentiation of circulating monocytes to fibroblasts after homing in the injured liver are discussed as important complementary mechanisms to enlarge the pool of (myo-)fibroblasts in the fibrosing liver. Among the molecular mediators, transforming growth factor-beta (TGF-,) plays a central role, which is controlled by the bone-morphogenetic protein (BMP)-7, an important antagonist of TGF-, action. The newly discovered pathways supplement the linear concept of HSC activation to myofibroblasts, point to fibrosis as a systemic response involving extrahepatic organs and reactions, add further evidence to a more or less uniform concept of organ fibrosis in general (e.g. liver, lung, kidney), and offer innovative approaches for the development of non-invasive biomarkers and antifibrotic trials. [source] Selegiline, an MAO-B inhibitor, attenuates airway smooth muscle contraction in the rat tracheaJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2004Maki Yoshimura Selegiline is widely used for Parkinson's disease and sometimes for Alzheimer's disease. It is reported to affect intracellular Ca2+ concentration. Since intracellular Ca2+ is partly regulated by phosphatidylinositol (PI) response and is important for smooth muscle contraction, selegiline may affect airway smooth muscle tension. We examined the effects of selegiline on acetylcholine (ACh)- and KCl-induced contractile and PI responses in rat trachea. The trachea was cut into 3-mm-wide ring segments or 1-mm-wide slices. ACh (3 ,M, 50% effective dose) or KCl (40mM) was added, and ring relaxation was induced by the addition of selegiline. Tracheal slices were incubated with [3H]myo -inositol and 3 ,M ACh in the presence of selegiline, and [3H]inositol monophosphate (IP1) was measured. Selegiline dose-dependently attenuated ACh- and KCl-induced tracheal ring contractions. Fifty-percent inhibitory doses (ID50) of selegiline against ACh- and KCl-induced contraction were 120±30 ,M and 80±20 ,M, respectively. Basal and ACh-induced IP1 accumulation were 2.20±0.20 Bq and 7.88±0.23 Bq, respectively, and selegiline at a dose of 1000 ,M attenuated ACh-induced IP1 accumulation (5.44±0.30 Bq). These results suggest that selegiline inhibits contractile responses through the inhibition of voltage-operated Ca2+ channels and the PI response. [source] Neonatal Alcohol-Induced Region-Dependent Changes in Rat Brain Neurochemistry Measured by High-Resolution Magnetic Resonance SpectroscopyALCOHOLISM, Issue 10 2008Shonagh K. O'Leary-Moore Background:, Maternal drinking during pregnancy can lead to a range of deleterious outcomes in the developing offspring that have been collectively termed fetal alcohol spectrum disorders (FASDs). There is interest and recognized value in using non-invasive neuroimaging techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) to characterize, respectively, structural and biochemical alterations in individuals with FASDs. To date, however, results with MRS have been inconsistent regarding the degree and/or nature of abnormalities. Methods:, High-resolution magic angle spinning (HR-MAS) proton (1H) MRS is an ex vivo neuroimaging technique that can acquire spectra in small punches of intact tissue, providing clinically relevant neurochemical information about discrete brain regions. In this study, HR-MAS 1H MRS was used to examine regional neurochemistry in frontal cortex, striatum, hippocampus, and cerebellum of young rats previously exposed to ethanol as neonates. Key neurochemicals of interest included N-acetyl-aspartate (NAA), glutamate, GABA, glutamine, creatine, choline and myo -inositol. Results:, Daily neonatal alcohol exposure from postnatal day 4 (PN4) through PN9 significantly reduced levels of NAA and taurine in the cerebellum and striatum, and induced sex-dependent reductions in cerebellar glutamate when measured on PN16. In addition, myo -inositol was significantly increased in cerebellum. The frontal cortex and hippocampus were virtually unaffected by this neonatal alcohol exposure. Conclusion:, Results of this research may have implications for understanding the underlying neurobiology associated with FASDs and aid in testing treatments in the future. Ongoing studies are assessing the developmental persistence of and/or maturational recovery from these changes. [source] Longitudinal Brain Metabolic Characterization of Chronic Alcoholics With Proton Magnetic Resonance SpectroscopyALCOHOLISM, Issue 9 2002Mitchell H. Parks Background Proton magnetic resonance spectroscopy may elucidate the molecular underpinnings of alcoholism-associated brain shrinkage and the progression of alcohol dependence. Methods Using proton magnetic resonance spectroscopy, we determined absolute concentrations of N -acetylaspartate (NAA), creatine/phosphocreatine (Cr), and choline (Cho)-containing compounds and myo -inositol (mI) in the anterior superior cerebellar vermis and frontal lobe white matter in 31 alcoholics and 12 normal controls. All patients were examined within 3 to 5 days of their last drink. Patients who did not relapse were again studied after 3 weeks and 3 months of abstinence by using an on-line repositioning technique that allows reliable localization of volumes of interest (VOIs). Results At 3 to 5 days after the last drink, frontal white matter metabolite concentrations were not significantly different from those of normal controls, whereas brain tissue in the VOI was reduced. Cerebellar [NAA] and [Cho] and brain and cerebellar volumes were decreased, but [Cr], [mI], and VOI brain tissue volume were not significantly different. Eight patients relapsed before 3 weeks (ER), 12 relapsed between 3 weeks and 3 months (LR), and 11 did not relapse (NR) during 3 months. Cerebellar [NAA] was reduced only in ER patients, despite the fact that ER patients drank for significantly fewer years and earlier in life than LR or NR patients. After 3 months, in the 11 continuously abstinent patients, cerebellar [NAA] and brain and cerebellar volumes increased; cerebellar [Cho], [Cr], and [mI] and VOI brain tissue did not change significantly. Conclusions Decreased [NAA] and [Cho] in cerebellar vermis indicate a unique sensitivity to alcohol-induced brain injury. Cerebellar [NAA] increased with abstinence, but reduced [Cho] persisted beyond 3 months. Further studies are needed to determine whether low cerebellar [NAA] is a risk factor for, or consequence of, malignant, early-onset alcoholism. [source] 1H chemical shifts in NMR: Part 22,,Prediction of the 1H chemical shifts of alcohols, diols and inositols in solution, a conformational and solvation investigationMAGNETIC RESONANCE IN CHEMISTRY, Issue 8 2005Raymond J. Abraham Abstract The 1H NMR spectra of a number of alcohols, diols and inositols are reported and assigned in CDCl3, D2O and DMSO- d6 (henceforth DMSO) solutions. These data were used to investigate the effects of the OH group on the 1H chemical shifts in these molecules and also the effect of changing the solvent. Inspection of the 1H chemical shifts of those alcohols which were soluble in both CDCl3 and D2O shows that there is no difference in the chemical shifts in the two solvents, provided that the molecules exist in the same conformation in the two solvents. In contrast, DMSO gives rise to significant and specific solvation shifts. The 1H chemical shifts of these compounds in the three solvents were analysed using the CHARGE model. This model incorporates the electric field, magnetic anisotropy and steric effects of the functional group for long-range protons together with functions for the calculation of the two- and three-bond effects. The long-range effect of the OH group was quantitatively explained without the inclusion of either the CO bond anisotropy or the COH electric field. Differential , and , effects for the 1,2-diol group needed to be included to obtain accurate chemical shift predictions. For DMSO solution the differential solvent shifts were calculated in CHARGE on the basis of a similar model, incorporating two-bond, three-bond and long-range effects. The analyses of the 1H spectra of the inositols and their derivatives in D2O and DMSO solution also gave the ring 1H,1H coupling constants and for DMSO solution the CHOH couplings and OH chemical shifts. The 1H,1H coupling constants were calculated in the CHARGE program by an extension of the cos2, equation to include the orientation effects of electronegative atoms and the CHOH couplings by a simple cos2, equation. Comparison of the observed and calculated couplings confirmed the proposed conformations of myo -inositol, chiro -inositol, quebrachitol and allo -inositol. The OH chemical shifts were also calculated in the CHARGE program. Comparison of the observed and calculated OH chemical shifts and CH. OH couplings suggested the existence of intramolecular hydrogen bonding in a myo -inositol derivative. Copyright © 2005 John Wiley & Sons, Ltd. [source] Fast CT-PRESS-based spiral chemical shift imaging at 3 TeslaMAGNETIC RESONANCE IN MEDICINE, Issue 5 2006Dirk Mayer Abstract A new sequence is presented that combines constant-time point-resolved spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the acquisition of multivoxel spectra without line splitting with a minimum total measurement time of less than 5 min for a field of view of 24 cm and a nominal 1.5 × 1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding steps in t1 (,t1 = 12.8 ms) and an average echo time of 151 ms, which was determined by simulating the CT-PRESS experiment for the spin systems of glutamate (Glu) and myo -inositol (mI). Signals from N-acetyl-aspartate, total creatine, choline-containing compounds (Cho), Glu, and mI were detected in a healthy volunteer with no or only minor baseline distortions within 14 min on a 3 T MR scanner. Magn Reson Med, 2006. © 2006 Wiley-Liss, Inc. [source] The glycosylphosphatidylinositol (GPI) biosynthetic pathway of bloodstream-form Trypanosoma brucei is dependent on the de novo synthesis of inositolMOLECULAR MICROBIOLOGY, Issue 1 2006Kirstee L. Martin Summary In bloodstream-form Trypanosoma brucei (the causative agent of African sleeping sickness) the glycosylphosphatidylinositol (GPI) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. The conundrum that GPI anchors could not be in vivo labelled with [3H]-inositol led us to hypothesize that de novo synthesis was responsible for supplying myo -inositol for phosphatidylinositol (PI) destined for GPI synthesis. The rate-limiting step of the de novo synthesis is the isomerization of glucose 6-phosphate to 1- d -myo -inositol-3-phosphate, catalysed by a 1- d -myo -inositol-3-phosphate synthase (INO1). When grown under non-permissive conditions, a conditional double knockout demonstrated that INO1 is an essential gene in bloodstream-form T. brucei. It also showed that the de novo synthesized myo -inositol is utilized to form PI, which is preferentially used in GPI biosynthesis. We also show for the first time that extracellular myo- inositol can in fact be used in GPI formation although to a limited extent. Despite this, extracellular inositol cannot compensate for the deletion of INO1. Supporting these results, there was no change in PI levels in the conditional double knockout cells grown under non-permissive conditions, showing that perturbation of growth is due to a specific lack of de novo synthesized myo -inositol and not a general inositol-less death. These results suggest that there is a distinction between de novo synthesized myo -inositol and that from the extracellular environment. [source] Association of mycothiol with protection of Mycobacterium tuberculosis from toxic oxidants and antibioticsMOLECULAR MICROBIOLOGY, Issue 6 2003Nancy A. Buchmeier Summary Mycothiol, MSH or 1d - myo -inosityl 2-(N -acetyl- l -cysteinyl)amido-2-deoxy- , - d -glucopyranoside, is an unusual conjugate of N -acetylcysteine (AcCys) with 1d - myo -inosityl 2-acetamido-2-deoxy-,- d -glucopyranoside (GlcN-Ins), and is the major low-molecular-mass thiol in mycobacteria. Mycothiol has antioxidant activity as well as the ability to detoxify a variety of toxic compounds. Because of these activities, MSH is a candidate for protecting Mycobacterium tuberculosis from inactivation by the host during infections as well as for resisting antituberculosis drugs. In order to define the protective role of MSH for M. tuberculosis, we have constructed an M. tuberculosis mutant in Rv1170, one of the candidate MSH biosynthetic genes. During exponential growth, the Rv1170 mutant bacteria produced , 20% of wild-type levels of MSH. Levels of the Rv1170 substrate, GlcNAc-Ins, were elevated, whereas those of the product, GlcN-Ins, were reduced. This establishes that the Rv1170 gene encodes for the major GlcNAc-Ins deacetylase activity (termed MshB) in the MSH biosynthetic pathway of M. tuberculosis. The Rv1170 mutant grew poorly on agar media lacking catalase and oleic acid, and had heightened sensitivities to the toxic oxidant cumene hydroperoxide and to the antibiotic rifampin. In addition, the mutant was more resistant to isoniazid, suggesting a role for MSH in activation of this prodrug. These data indicate that MSH contributes to the protection of M. tuberculosis from oxidants and influences resistance to two first-line antituberculosis drugs. [source] Reduced N -acetylaspartate is consistent with axonal dysfunction in cerebral small vessel diseaseNMR IN BIOMEDICINE, Issue 3 2009Arani Nitkunan Abstract Background: Cerebral small vessel disease (SVD) is an important cause of cognitive impairment, but the pathophysiological mechanisms remain unclear. We used 1H MRS to investigate brain metabolic differences between patients with SVD and controls and correlated this with cognition. Methods: 35 patients with SVD (lacunar stroke and radiological evidence of confluent leukoaraiosis) and 35 controls underwent multi-voxel spectroscopic imaging of white matter to obtain absolute metabolite concentrations of N -acetylaspartate (NAA), total creatines, total cholines, myo -inositol, and lactate. A range of cognitive tests was performed on patients with SVD, and composite scores were calculated. Results: Scans of sufficient quality for data analysis were available in 29 cases and 35 controls. NAA was significantly reduced in patients compared with controls (lower by 7.27%, P,=,0.004). However, when lesion load within each individual voxel (mean 22% in SVD vs 5% in controls, P,<,0.001) was added as a covariate, these differences were no longer significant, suggesting that the metabolite differences arose primarily from differences in lesioned tissue. In patients with SVD, there was no correlation between cognitive scores and any brain metabolite. No lactate, an indicator of anaerobic metabolism, was detected. Conclusions: The most consistent change in SVD is a reduction in NAA, a marker of neuronal integrity. The lack of correlation with cognition does not support the use of MRS as a surrogate disease marker. Copyright © 2008 John Wiley & Sons, Ltd. [source] Bifunctional indole-3-acetyl transferase catalyses synthesis and hydrolysis of indole-3-acetyl- myo -inositol in immature endosperm of Zea maysPHYSIOLOGIA PLANTARUM, Issue 2 2003Stanislaw Kowalczyk 1- O -(indole-3-acetyl)- , - d -glucose: myo -inositol indoleacetyl transferase (IA- myo -inositol synthase) is an important enzyme in IAA metabolism. This enzyme catalyses the transfer of the indole acetyl (IA) moiety from 1- O -(indole-3-acetyl)- , - d -glucose to myo -inositol to form IA- myo- inositol and glucose. IA- myo -inositol synthase was purified to an electrophoretically homogenous state from maize liquid endosperm by fractionation with ammonium sulphate, anion-exchange, adsorption on hydroxylapatite, affinity chromatography on ConA-Sepharose, preparative PAGE and isoelectric focusing. We thus obtained two enzyme preparations which differ in their Rf on 8% polyacrylamide gel. The preparation of Rf 0.36 contained a single 56.4 kDa polypeptide, whereas the preparation of Rf 0.39 consisted of two polypeptides of 56.4 and 53.5 kDa. Both purified preparations of IAInos synthase also exhibited the activity of an IAInos hydrolase, showing that the dual activity was associated with a single protein. Results of gel filtration and analytical SDS-PAGE suggest that the native enzyme exists as both a monomeric (65 kDa) and homo- or heterodimeric form (110,130 kDa). Analysis of peptide maps and amino acid sequences of two 21 amino-acid peptides showed that polypeptides of 56.4 and 53.5 kDa have the same primary structure and that the 3 kDa difference in molecular mass is probably caused by different glycosylation levels. Comparison of this partial and internal amino acid sequence with sequences of other plant acyltransferases indicated similarity to several proteins which belonged to the serine carboxypeptidase-like (SCPL) acyltransferase family. [source] The synergistic effects of sugar and abscisic acid on myo -inositol-1-phosphate synthase expressionPHYSIOLOGIA PLANTARUM, Issue 4 2002Kaoru T. Yoshida 1L- myo -inositol-1-phosphate [Ins(1)P1] synthase (EC 5.5.1.4) catalyses the formation of Ins(1)P1 from glucose-6-phosphate, the first step in the biosynthesis of myo -inositol. Ins(1)P1 is a precursor of phytin (inositol hexakisphosphate), a storage form of phosphate and cations in seeds. Since sucrose and abscisic acid (ABA) are known to affect synthesis of storage compounds in seeds, we investigated the effects of ABA and sucrose on Ins(1)P1 synthase gene (RINO1) expression in cultured cells derived from the scutellum of mature rice seeds. Higher levels of RINO1 transcript accumulation were evident after treatment with either sucrose (10,100 mM) or ABA (10,8M to 10,4M). Glucose was also effective in the upregulation, whereas mannitol was not, suggesting that sucrose and glucose acted as metabolizable sugars and not as osmotica. Treatment with ABA and sucrose together resulted in much higher levels of transcript accumulation, suggesting a synergistic induction of the Ins(1)P1 synthase gene. [source] Rat lens aldose reductase inhibitory constituents of Nelumbo nucifera stamensPHYTOTHERAPY RESEARCH, Issue 10 2006Soon Sung Lim Abstract Aldose reductase, the principal enzyme of the polyol pathway, has been shown to play an important role in the complications associated with diabetes. A methanol extract of the stamens of Nelumbo nucifera Gaertn. was shown to exert an inhibitory effect on rat lens aldose reductase (RLAR), and thus was fractionated using several organic solvents, including dichloromethane, ethyl acetate and n -butanol. The ethyl acetate-soluble fraction, which manifested potent RLAR-inhibitory properties, was then purified further via repeated measures of silica gel and Sephadex LH-20 column chromatography. Thirteen flavonoids: kaempferol (1) and seven of its glycosides (2,9), myricetin 3,,5,-dimethylether 3- O - , - d -glucopyranoside (10), quercetin 3- O - , - d -glucopyranoside (11) and two isorhamnetin glycosides (12, 13) were isolated from N. nucifera, as well as four non-flavonoid compounds: adenine (14), myo -inositol (15), arbutin (16) and , -sitosterol glucopyranoside (17). These compounds were all assessed with regard to their RLAR-inhibitory properties. Among the isolated flavonoids, those harboring 3- O - , - l -rhamnopyranosyl-(1,6)- , - d -glucopyranoside groups in their C rings, including kaempferol 3- O - , - l -rhamnopyranosyl-(1,6)- , - d -glucopyranoside (5) and isorhamnetin 3- O - , - l -rhamnopyranosyl-(1,6)- , - d -glucopyranoside (13), were determined to exhibit the highest degree of rat lens aldose reductase inhibitory activity in vitro, evidencing IC50 values (concentration required for a 50% inhibition of enzyme activity) of 5.6 and 9.0 µm, respectively. Copyright © 2006 John Wiley & Sons, Ltd. [source] Generation of stable ,low phytic acid' transgenic rice through antisense repression of the 1d - myo -inositol 3-phosphate synthase gene (RINO1) using the 18-kDa oleosin promoterPLANT BIOTECHNOLOGY JOURNAL, Issue 1 2009Mio Kuwano Summary Phytic acid acts as the major storage form of phosphorus in plant seeds and is poorly digested by monogastric animals. The degradation of phytic acid in animal diets is necessary to overcome both environmental and nutritional issues. The enzyme 1d - myo -inositol 3-phosphate [Ins(3)P1] synthase (EC 5.5.1.4) catalyses the first step of myo -inositol biosynthesis and directs phytic acid biosynthesis in seeds. The rice Ins(3)P1 synthase gene (RINO1) is highly expressed in developing seed embryos and in the aleurone layer, where phytic acid is synthesized and stored. In rice seeds, 18-kDa oleosin (Ole18) is expressed in a seed-specific manner, and its transcripts are restricted to the embryo and the aleurone layer. Therefore, to effectively suppress phytic acid biosynthesis, antisense RINO1 cDNA was expressed under the control of the Ole18 promoter, directing the same spatial pattern in seeds as RINO1 in transgenic rice plants. The generated transgenic rice plants showed strong ,low phytic acid' (lpa) phenotypes, in which seed phytic acid was reduced by 68% and free available phosphate was concomitantly increased. No negative effects on seed weight, germination or plant growth were observed. The available phosphate levels of the stable transgenic plants surpassed those of currently available rice lpa mutants. [source] Characterization of the MIPS gene family in Glycine maxPLANT BREEDING, Issue 5 2006A. S. Chappell Abstract Phytic acid (myo -inositol-1,2,3,4,5,6-hexakisphosphate) is the primary storage component of phosphorus in plant seeds. The first step in phytic acid biosynthesis is the de novo synthesis of myo -inositol, which is catalyzed by the enzyme D -myo -inositol 3-phosphate synthase (MIPS EC 5.5.1.4). Previous work detected four MIPS genes in soybean (Glycine max). However, only a limited amount of data were available for the MIPS gene family and some of the data were conflicting. The work described here clears up these data and characterizes the MIPS gene family for the purposes of reverse genetic technologies. The complete genomic sequence of all four genes was determined and their expression profile was examined by quantitative real-time reverse transcription-polymerase chain reaction. Our results indicate that the four MIPS genes are highly conserved and temporally and spatially expressed. The MIPS gene family in the low phytic acid soybean line, CX1834, was also characterized since this line displays a phenotype similar to previously characterized MIPS mutants. These data demonstrate that mutations in MIPS genes are not the cause of the low phytic acid phenotype. [source] | |||||||||||||||||||