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Mannitol
Kinds of Mannitol Terms modified by Mannitol Selected AbstractsHyperosmotic mannitol induces Src kinase-dependent phosphorylation of ,-catenin in cerebral endothelial cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2005Attila Farkas Abstract Mannitol, which is a cell-impermeable and nontoxic polyalcohol, has been shown to be a useful tool for reversible opening of the blood,brain barrier (BBB). Despite successful clinical trials, the molecular mechanism of the mannitol-induced changes in cerebral endothelial cells (CECs) are poorly understood. For our experiments, we used CECs in culture, which were treated with different, clinically relevant concentrations of mannitol. We found that mannitol induced a rapid, concentration-dependent, and reversible tyrosine phosphorylation of a broad range of proteins between 50 and 190 kDa. One of the targets of tyrosine phosphorylation turned out to be the adherens junction protein ,-catenin. Phosphorylation of ,-catenin on tyrosine residues caused its subcellular redistribution and its dissociation from cadherin and ,-catenin as shown by coimmunoprecipitation studies. All these effects could be inhibited by the Src kinase inhibitor PP-1 but not by the Erk inhibitor U0126, the Rho kinase inhibitor Y27632, or the calcium channel blocker verapamil. Because ,-catenin is a key component of the junctional complex, its Src-mediated phpsphorylation may play an important role in the mannitol induced reversible opening of the BBB. © 2005 Wiley-Liss, Inc. [source] Terahertz spectroscopy to identify the polymorphs in freeze-dried mannitolJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 2 2010Reshmi Chakkittakandy Abstract We show how terahertz time-domain spectroscopy (THz-TDS) in the range from 0.1 to 7.5,THz can be used to identify the polymorphs of Mannitol, a frequently used excipient in the freeze drying industry. The results are subsequently used to study the effect that different freeze drying techniques have on the formation of these polymorphs. We find that, depending on the freeze-drying technique, the Mannitol either crystallizes in the , form, or in a mixture of both the , form and the , form. The results are in agreement with conventional X-ray diffraction measurements used to identify the polymorphs. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:932,940, 2010 [source] Mannitol,sucrose mixtures,versatile formulations for protein lyophilizationJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 4 2002Robert E. Johnson Abstract Mixtures of sucrose (a lyoprotectant) and mannitol (a bulking agent) have been investigated as excipients for the lyophilization of proteins. Four proteins under development have been successfully lyophilized in a formulation of 4% mannitol and 1% sucrose using a lyophilization cycle that produces a cake of crystalline mannitol and amorphous sucrose. The crystalline mannitol allows primary drying to be performed with a product temperature of ,10°C even though the sucrose is amorphous and, by itself, would have required primary drying below ,35°C to avoid cake collapse. Formation of an unstable mannitol hydrate is avoided by conducting secondary drying at 40°C or higher. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 91: 914,922, 2002 [source] Intraoperative hyponatremia during craniofacial surgeryPEDIATRIC ANESTHESIA, Issue 4 2009K. RANDO MD Summary Background:, Hyponatremia is an important cause of morbidity in some groups of hospitalized children. Our aim is to describe the incidence and severity of intraoperative hyponatremia in children undergoing craniofacial surgery, and determine the associated risk factors. Methods:, A descriptive retrospective study of children who underwent primary craniofacial surgery between March 1994 and February 2008 was performed. All administered fluids contained a minimum sodium concentration of 140 mmol·l,1. Hyponatremia was classified as follows: severe ,125 mmol·l,1; moderate 126,130 mmol·l,1; and, mild 131,134 mmol·l,1. Results:, Hundred and seven cases are reported. Severe, moderate and mild intraoperative hyponatremia occurred in 14 (13%), 21 (19%) and 23 (22%) children respectively. Mannitol was given to 31 (29%) children, but was not associated with the development of hyponatremia. Neither the type nor duration of surgery, type of fluid replacement nor hourly urinary output, was associated with development of hyponatremia. Most episodes of significant intraoperative hyponatremia (44%) were detected between the 2nd and the 4th hour of surgery. There were no identified neurological sequelae (e.g. coma, neurological deficit) attributable to the hyponatremia. Conclusion:, Despite strict avoidance of low sodium solutions (<140 mmol·l,1), hyponatremia occurs frequently in children undergoing craniofacial surgery in our practice; and is unrelated to the administration of mannitol. Although the mechanisms are yet to be determined, anesthesiologists should be aware of this issue and be prepared to monitor and treat this potentially serious complication. [source] Expression of a celery mannose 6-phosphate reductase in Arabidopsis thaliana enhances salt tolerance and induces biosynthesis of both mannitol and a glucosyl-mannitol dimerPLANT CELL & ENVIRONMENT, Issue 2 2003G. ZHIFANG ABSTRACT Mannitol, a sugar alcohol that may serve as a compatible solute to cope with salt stress, is synthesized via the action of a mannose-6-phosphate reductase (M6PR) in celery (Apium graveolens L). In contrast to previous approaches that have used a bacterial gene to engineer mannitol biosynthesis in plants and other organisms, Arabidopsis thaliana, a non-mannitol producer, was transformed with the celery leaf M6PR gene under control of the CaMV 35S promotor. In all independent Arabidopsis M6PR transformants, mannitol accumulated throughout the plants in amounts ranging from 0·5 to 6 µmol g,1 fresh weight. A novel compound, not found in either celery or Arabidopsis, 1-O- , - d -glucopyranosyl- d -mannitol, also accumulated in vegetative tissues of mature plants in amounts up to 4 µmol g,1 fresh weight, but not in flowers and seeds. In the absence of NaCl, all transformants were phenotypically the same as the wild type; however, in the presence of NaCl, mature transgenic plants showed a high level of salt tolerance, i.e. growing, completing normal development, flowering, and producing seeds in soil irrigated with 300 mm NaCl in the nutrient solution. These results demonstrate a major role in developing salt-tolerant plants by means of introducing mannitol biosynthesis using M6PR. [source] Comparison of ceftibuten transport across Caco-2 cells and rat jejunum mounted on modified ussing chambersBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2003R.M. Menon Abstract Ceftibuten uptake into Caco-2 cells and intestinal brush border membrane vesicles is mediated by the dipeptide transport system (PEPT1). The apical to basolateral transport characteristics of ceftibuten across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was examined. Mannitol was used as a paracellular marker along with trans-epithelial electrical resistance (TEER) for monitoring tight junction permeability. Transport across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was linear across the concentration range 0.25,10 mm. The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco-2 cells. At a donor concentration of 0.25 mm, ceftibuten transport across Caco-2 cells was found to be pH dependent. Glycyl proline, a dipeptide, and 2,4- dinitrophenol, an energy poison, caused a reduction in the permeability of 0.25 mm ceftibuten across Caco-2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 mm, passive paracellular transport accounts for about 60% and the active carrier mediated mechanism accounts for about 40% of ceftibuten transport across Caco-2 cells. None of the inhibitors however, had a significant effect on ceftibuten transport across rat jejunum mounted on a modified Ussing chamber at a donor concentration of 0.25 mm. In the concentration range 0.25,10 mm, ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco-2 cells. Copyright © 2003 John Wiley & Sons, Ltd. [source] Disconnect between standardized field-based testing and mannitol challenge in Scottish elite swimmersCLINICAL & EXPERIMENTAL ALLERGY, Issue 5 2010K. L. Clearie Summary Background Elite swimmers have high rates of rhinoconjunctivitis and exercise-induced bronchoconstriction. Moreover, exposure to chlorine and chlorine metabolites is known to induce bronchial hyper-reactivity. Objective To assess the early and late effects of chlorine and exercise on the unified airway of elite swimmers, and to compare the response to mannitol and field-based exercise challenge. Methods The Scottish national squad underwent exhaled tidal (FENO) and nasal (NNO) nitric oxide measurement, peak nasal inspiratory flow (PNIF), and forced expiratory volume in 1 s before, immediately after, and 4,6 h post-swimming. A sport-specific exercise test was carried out during an intensive lactate set (8 min at 80% maximum hear rate). All swimmers underwent mannitol challenge, and completed a health questionnaire. Results N=61 swimmers were assessed: 8/59 (14%) of swimmers had a positive mannitol challenge. Nine out of 57 (16%) of swimmers had a positive exercise test. Only one swimmer was positive to both. Swimmers with a positive mannitol had a significantly higher baseline FENO (37.3 vs. 18.0 p.p.b., P=0.03) than those with a positive exercise challenge. A significant decrease in FENO was observed pre vs. immediate and delayed post-chlorine exposure: mean (95% CI) 18.7 (15.9,22.0) p.p.b. vs. 15.9 (13.3,19.1) p.p.b. (P<0.01), and 13.9 (11.5,16.7) p.p.b. (P<0.01), respectively. There were no significant differences in NNO. Mean PNIF increased from 142.4 L/min (5.8) at baseline to 162.6 L/min (6.3) immediately post-exposure (P<0.01). Delayed post-exposure PNIF was not significantly different from pre-exposure. Conclusions No association was found between mannitol and standardized field-based testing in elite swimmers. Mannitol was associated with a high baseline FENO; however, exercise/chlorine challenge was not. Thus, mannitol may identify swimmers with a ,traditional' inflammatory asthmatic phenotype, while field-based exercise/chorine challenge may identify a swimmer-specific bronchoconstrictor response. A sustained fall in FENO following chlorine exposure suggests that a non-cellular, perhaps neurogenic, response may be involved in this group of athletes. Cite this as: K. L. Clearie, P. A. Williamson, S. Vaidyanathan, P. Short, A. Goudie, P. Burns, P. Hopkinson, K. Meldrum, L. Howaniec and B. J. Lipworth, Clinical & Experimental Allergy, 2010 (40) 731,737. [source] In vivo evaluation of a nasal insulin delivery system based on thiolated chitosanJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 11 2006Alexander H. Krauland Abstract The aim of this study was the preparation and in vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. 2-Iminothiolane was covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited 304.9,±,63.5 µmol thiol groups per gram polymer. Microparticles were prepared via a new precipitation-micronization technique. The microparticulate delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito-TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins administered nasally to rats led to an absolute bioavailability of 6.9,±,1.5%. The blood glucose level decreased for more than 2 h and the calculated absolute pharmacological efficacy was 4.9,±,1.4%. Chito/Ins, in comparison, displayed a bioavailability of 4.2,±,1.8% and a pharmacological efficacy of 0.7,±,0.6%. Mannitol/Ins showed a bioavailability of 1.6,±,0.4% and no reduction of the blood glucose level at all. According to these findings microparticles comprising chitosan-TBA seem to have substantial higher potential for nasal insulin administration than unmodified chitosan. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2463,2472, 2006 [source] Increased intestinal permeability and NOD2 variants in familial and sporadic Crohn's diseaseALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006R. D'INCŔ Summary Background Abnormal barrier function may be genetically determined in Crohn's disease. Aim To examine the role of abnormal intestinal permeability in genetic predisposition in multiplex vs. sporadic Crohn's disease families. Methods Intestinal permeability was measured in patients, relatives and partners by means of lactulose/mannitol test. Healthy subjects from the hospital staff served as controls. CARD15 mutations were investigated in sporadic and familial Crohn's disease patients and in a group of blood donors. Results The median lactulose/mannitol ratio was increased significantly in Crohn's disease patients vs. their relatives [0.03 (0.01,0.24) vs. 0.01 (0.003,0.19), P = 0.005]. The percentage of abnormal tests was significantly higher in familial vs. sporadic first-degree relatives of Crohn's disease patients (29% vs. 11%, P = 0.0281). Abnormal permeability occurred significantly more frequent in patients with familial Crohn's disease carrying the frameshift mutation. The frameshift mutation 3020insC was associated with increased permeability in 75% in the multiplex and in 61% of the sporadic CD patients. One partner had abnormal lactulose/mannitol ratio. Conclusion Intestinal permeability is raised in Crohn's disease patients and relatives, with higher rates in familial vs. sporadic healthy relatives. CARD15 mutations are associated with abnormal permeability in ileal Crohn's disease. [source] Mechanisms of transjunctional transport of NaCl and water in proximal tubules of mammalian kidneysACTA PHYSIOLOGICA, Issue 1 2002F. KIILArticle first published online: 30 APR 200 ABSTRACT Tight junctions and the intercellular space of proximal tubules are not accessible to direct measurements of fluid composition and transport rates, but morphological and functional data permit analysis of diffusion and osmosis causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses through tight junctions along a chloride gradient, but against a sodium gradient. Calculation in terms of modified Nernst,Fick diffusion equation after eliminating electrical terms shows that transport rates (300,500 pmol min,1 mm,1 tubule length) and transepithelial voltage of +2 mV are in agreement with observations. Diffusion coefficients are Dtj=1500 ,m2 s,1 in the S1 segment, and Dtj=90,100 ,m2 s,1 in the S2 segment where apical intercellular NaCl concentration is 132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions with gap distance 6 Ĺ are impermeable to mannitol (effective molecular radius 4 Ĺ); reflection coefficients are ,=0.92 for NaHCO3 and ,=0.28 for NaCl, because of difference in anion size. The osmotic force is provided by a difference in effective transjunctional osmolality of 10 mOsm kg,1 in the S1 segment and 30 mOsm kg,1 in the S2 segment, where differences in transjunctional concentration contribute with 21 mOsm kg,1 for NaHCO3 and ,4 mOsm kg,1 for NaCl. Transjunctional difference of 30 mOsm kg,1 causes a volume flow of 2 nL min,1 mm,1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow and diffusive and convective transport of NaCl. In conclusion, transjunctional diffusion and osmosis along gradients generated by transcellular transport of other solutes account for all NaCl transport in proximal tubules. [source] Solubility studies on valdecoxib in the presence of carriers, cosolvents, and surfactantsDRUG DEVELOPMENT RESEARCH, Issue 1 2004Kashappa Goud H. Desai Abstract Enhancement of the solubility of valdecoxib was examined using a series of hydrophilic carriers (mannitol, polyethylene glycol (PEG) 4000, PEG 6000, PEG 8000, and urea), surfactants (Tween-20, Tween-80, and sodium lauryl sulfate [SLS]) and cosolvents (ethanol, methanol, and glycerol) at 37°C. The solubility of valdecoxib could be enhanced significantly using PEG 4000 as a carrier, ethanol as cosolvent, and SLS as a surfactant. Because the solubility of valdecoxib increased dramatically in the presence of polyethylene glycols, these are suitable dispersing agents for preparing solid dispersions containing valdecoxib. Gibbs free energy (,G) values were all negative for all hydrophilic carriers tested, indicating the spontaneous nature of valdecoxib solubilisation. Among the cosolvents, ethanol exhibited higher solubilization potential than methanol and glycerol. As the dielectric constant of the cosolvent,water mixtures decreased, the solubility of valdecoxib increased. Finally, SLS exerted maximum solubilization of valdecoxib when compared to Tween-20 or Tween-80. The crystallinity of valdecoxib was explored by X-ray diffraction study and showed numerous crystalline peaks. Examination of surface morphology by scanning electron microscopy depicted a near spherical shape of valdecoxib with irregular surface characteristics. Drug Dev. Res. 62:41,48, 2004. © 2004 Wiley-Liss, Inc. [source] Determination of neutral carbohydrates by CZE with direct UV detectionELECTROPHORESIS, Issue 17 2007Stella Rovio Abstract A new CZE method relying on in-capillary reaction and direct UV detection at the wavelength 270,nm is presented for the simultaneous separation of the neutral carbohydrates xylitol, D -(,)-mannitol, sucrose, D -(+)-fucose, D -(+)-cellobiose, D -(+)-galactose, D -(+)-glucose, L -rhamnose, D -(+)-mannose, D -(,)-arabinose, D -(+)-xylose, and D -(,)-ribose. The alkaline electrolyte solution was prepared of 130,mM sodium hydroxide and 36,mM disodium hydrogen phosphate dihydrate. Separation of the sample mixture was achieved within 35,min. Calibration plots were linear in the range of 0.05,3,mM. Reproducibility of migration times was between 0.3 and 1.1%, and the detection limits for the analytes were 0.02 and 0.05,mM. The optimized method was applied for the determination of neutral monosaccharides in lemon, pineapple, and orange juices and a cognac sample. The methodology is fast since no other sample preparation except dilution is required. [source] Review article: Hypertonic saline use in the emergency departmentEMERGENCY MEDICINE AUSTRALASIA, Issue 4 2008Colin J Banks Abstract Hypertonic saline (HS) is being increasingly used for the management of a variety of conditions, most notably raised intracranial pressure. This article reviews the available evidence on HS solutions as they relate to emergency medicine, and develops a set of recommendations for its use. To conclude, HS is recommended as an alternative to mannitol for treating raised intracranial pressure in traumatic brain injury. HS is also recommended for treating severe and symptomatic hyponatremia, and is worth considering for both recalcitrant tricyclic antidepressant toxicity and for cerebral oedema complicating paediatric diabetic ketoacidosis. HS is not recommended for hypovolaemic resuscitation. [source] Optimization of culture conditions for glucose oxidase production by a Penicillium chrysogenum SRT 19 strainENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 1 2010Ragini G. Bodade Abstract The enzyme glucose oxidase (GOD) has been used for a variety of biotechnological applications in food and pharmaceutical industries. In this study, the optimization of extracellular GOD production was carried out in a Penicillium chrysogenum SRT 19 strain isolated from contaminated and decaying cheese samples. Maximum GOD production was attained at pH 6 and 20°C in fermentation broth after 72,h of incubation. The effects of metal ions and sugars were screened for the induction of higher GOD production. The results revealed that glucose and lactose give the highest production of enzyme (0.670 and 0.552,U/mL, respectively) as compared with other sugars (sucrose, cellulose, mannitol and fructose). Out of the seven metal ions studied, CaCO3 (1.123,U/mL) and FeSO4 (0.822,U/mL) act as modulators, while MgSO4 (0.535,U/mL), CuSO4 (0.498,U/mL), HgCl2 (0.476,U/mL), ZnSO4 (0.457,U/mL) and BaSO4 (0.422,U/mL) yield lower production. The study therefore suggests that a strain of P. chrysogenum SRT 19 can be used as a new strain for GOD production. [source] Universal and species-specific bacterial ,fungiphiles' in the mycospheres of different basidiomycetous fungiENVIRONMENTAL MICROBIOLOGY, Issue 2 2009J. A. Warmink Summary In previous work, several bacterial groups that show a response to fruiting bodies (the mycosphere) of the ectomycorrhizal fungus Laccaria proxima were identified. We here extend this work to a broader range of fungal fruiting bodies sampled at two occasions. PCR-DGGE analyses showed clear effects of the mycosphere of diverse fungi on the total bacterial and Pseudomonas communities in comparison with those in the corresponding bulk soil. The diversities of the Pseudomonas communities increased dramatically in most of the mycospheres tested, which contrasted with a decrease of the diversity of the total bacterial communities in these habitats. The data also indicated the existence of universal (i.e. Pseudomonas poae, P. lini, P. umsongensis, P. corrugata, P. antarctica and Rahnella aquatilis) as well as specific (i.e. P. viridiflava and candidatus Xiphinematobacter americani) fungiphiles, defined as bacteria adapted to the mycospheres of, respectively, three or more or just one fungal species. The selection of such fungiphiles was shown to be strongly related to their capacities to use particular carbonaceous compounds, as evidenced using principal components analyses of BIOLOG-based substrate utilization tests. The differentiating compounds, i.e. l -arabinose, l -leucine, m-inositol, m-arabitol, d -mannitol and d -trehalose, were tentatively linked to compounds known to occur in mycosphere exudates. [source] A strain isolated from gas oil-contaminated soil displays chemotaxis towards gas oil and hexadecaneENVIRONMENTAL MICROBIOLOGY, Issue 10 2003Mariana P. Lanfranconi Summary In this report we describe the isolation of a strain from soil contaminated with gas oil by taking bacteria from a chemotactic ring on gas oil-containing soft agar plates. Partial 16 S rDNA sequencing of the isolated strain showed 99.1% identity with Flavimonas oryzihabitans. It was not only able to degrade different aliphatic hydrocarbons but it was also chemotactic towards gas oil and hexadecane, as demonstrated by the use of three different chemotaxis methods, such as agarose plug and capillary assays and swarm plate analysis. In addition, the strain was chemotactic to a variety of carbon sources that serve as growth substrates, including glucose, arabinose, mannitol, glycerol, gluconate, acetate, succinate, citrate, malate, lactate and casaminoacids. This is the first report on chemotaxis of a hydrocarbon-degrading bacterium towards a pure alkane, such as hexadecane. The fact that environmental isolates show chemotaxis towards contaminant/s present in the site of isolation suggests that chemotaxis might enhance biodegradation by favouring contact between the degrading microorganism and its substrate. [source] Mechanism of DNA damage by cadmium and interplay of antioxidant enzymes and agentsENVIRONMENTAL TOXICOLOGY, Issue 2 2007Veera L. D. Badisa Abstract Cadmium is an environmental toxicant, which causes cancer in different organs. It was found that it damages DNA in the various tissues and cultured cell lines. To investigate the mechanism of DNA damage, we have studied the effect of cadmium-induced DNA damage in plasmid pBR322 DNA, and the possible ameliorative effects of antioxidative agents under in vitro conditions. It was observed that cadmium alone did not cause DNA damage. However, it caused DNA damage in the presence of hydrogen peroxide, in a dose dependent manner, because of production of hydroxyl radicals. Findings from this study show the conversion of covalently closed circular double-stranded pBR 322 DNA to the open circular and linear forms of DNA when treated with 10 ,M cadmium and various concentrations of H2O2. The conversion was due to nicking in DNA strands. The observed rate of DNA strand breakage was dependent on H2O2 concentration, temperature, and time. Metallothionein I failed to prevent cadmium-induced DNA nicking in the presence of H2O2. Of the two antioxidant enzymes (catalase and superoxide dismutase) studied, only catalase conferred significant (50,60%) protection. EDTA and DMSO exhibited protection similar to catalase, while mannitol showed only about 20% protection against DNA damage. Ethyl alcohol failed to ameliorate cadmium-induced DNA strands break. From this study, it is plausible to infer that cadmium in the presence of hydrogen peroxide causes DNA damage probably by the formation of hydroxyl ions. These results may indicate that cadmium in vivo could play a major role in the DNA damage induced by oxidative stress. © 2007 Wiley Periodicals, Inc. Environ Toxicol 22: 144,151, 2007. [source] Atrazine increases the sodium absorption in frog (Rana esculenta) skinENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 2 2006Giuseppe Cassano Abstract The presence of atrazine in agricultural sites has been linked to the decline in amphibian populations. The efforts of the scientific community generally are directed toward investigating the long-term effect of atrazine on complex functions (reproduction or respiration), but in the present study, we investigated the short-term effect on the short-circuit current (ISC), a quantitative measure of the ion transport operated by frog (Rana esculenta) skin. Treatment with 5 ,M atrazine (1.08 mg/L) does not affect the transepithelial outfluxes of [14C]mannitol or [14C]urea; therefore, atrazine does not damage the barrier properties of frog skin. Atrazine causes a dose-dependent increase in the short-circuit current, with a minimum of 4.64 ± 0.76 ,A/cm2 (11.05% ± 1.22%) and a maximum of 12.7 ± 0.7 ,A/cm2 (35% ± 2.4%) measured at 10 nM and 5 ,M, respectively. An increase in ISC also is caused by 5 ,M ametryne, prometryn, simazine, terbuthylazine, or terbutryn (other atrazine derivatives). In particular, atrazine increases the transepithelial 22Na+ influx without affecting the outflux. Finally, stimulation of ISC by atrazine is suppressed by SQ 22536, H89, U73122, 2-aminoethoxydiphenyl borate, and W7 (blockers of adenylate cyclase, protein kinase A, phospholipase C, intracellular Ca2+ increase, and calmodulin, respectively), whereas indomethacin and calphostin C (inhibitors of cyclooxygenase and protein kinase C, respectively) have no effect. [source] Blood,brain barrier damage and brain penetration of antiepileptic drugs: Role of serum proteins and brain edemaEPILEPSIA, Issue 4 2009Nicola Marchi Summary Purpose:, Increased blood,brain barrier (BBB) permeability is radiologically detectable in regions affected by drug-resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy-glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage. Methods:, In vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3-sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively. Results:, BBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain. Discussion:, After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug-resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies. [source] Differential effects of low glucose concentrations on seizures and epileptiform activity in vivo and in vitroEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Anne Kirchner Abstract In vivo, severe hypoglycemia is frequently associated with seizures. The hippocampus is a structure prone to develop seizures and seizure-induced damage. Patients with repeated hypoglycemic episodes have frequent memory problems, suggesting impaired hippocampal function. Here we studied the effects of moderate hypoglycemia on primarily generalized flurothyl-induced seizures in vivo and, using EEG recordings, we determined involvement of the hippocampus in hypoglycemic seizures. Moderate systemic hypoglycemia had proconvulsant effects on flurothyl-induced clonic (forebrain) seizures. During hypoglycemic seizures, seizure discharges were recorded in the hippocampus. Thus, we continued the studies in combined entorhinal cortex,hippocampus slices in vitro. However, in vitro, decreases in extracellular glucose from baseline 10 mm to 2 or 1 mm did not induce any epileptiform discharges. In fact, low glucose (2 and 1 mm) attenuated preexisting low-Mg2+ -induced epileptiform activity in the entorhinal cortex and hippocampal CA1 region. Osmolarity compensation in low-glucose solution using mannitol impaired slice recovery. Additionally, using paired-pulse stimuli we determined that there was no impairment of GABAA inhibition in the dentate gyrus during glucopenia. The data strongly indicate that, although forebrain susceptibility to seizures is increased during moderate in vivo hypoglycemia and the hippocampus is involved during hypoglycemic seizures, glucose depletion in vitro contributes to an arrest of epileptiform activity in the system of the entorhinal cortex,hippocampus network and there is no impairment of net GABAA inhibition during glucopenia. [source] Asymmetric Synthesis of ES-285, an Anticancer Agent Isolated from Marine SourcesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 35 2009Ana C. Allepuz Abstract The asymmetric synthesis of (2S,3R)-2-amino-3-octanedecanol hydrochloride (ES-285·HCl) was achieved in eight steps in ca. 38,% overall yield from the N -benzylimine-derived from (R)-2,3- O -isopropylidene glyceraldehyde, which is easily available on gram scale from the inexpensive precursor D -mannitol. Highly diastereoselective addition of methylmagnesium bromide to the N -benzylimine was the key step to create the vic -amino alcohol moiety with the appropriate configuration. Regioselective ring opening of an intermediate aminoepoxide enabled the introduction of the long hydrocarbon chain at C4.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis of C-Nucleosidic ATP Mimics as Potential FGFR3 InhibitorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2006Patricia Busca Abstract Receptor tyrosine kinases (RTKs) play an important role in signal transduction pathways, and in particular, FGFR3 is one of the four RTKs related to the fibroblast growth factor family. This paper describes the synthesis of C-nucleosidic ATP mimics, as potential FGFR3 inhibitors, by nucleophilic epoxide ring-opening followed by in situ O -heterocyclization of 1,2:5,6-dianhydro-3,4-di- O -benzyl- D -mannitol or L -iditol. Cesium carbonate [Cs2CO3] was found to be the best catalyst for the reaction of purine derivatives with these bis-epoxides. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] Kinetics of Thyroxine (T4) and Triiodothyronine (T3) Transport in the Isolated Rat HeartEXPERIMENTAL PHYSIOLOGY, Issue 1 2001Mirko A. Rosic The dynamics and kinetics of thyroid hormone transport in the isolated rat heart were examined using the modified unidirectional paired tracer dilution method. The uptake of 125I-thyroxine (125I-T4) and 125I-triiodothyronine (125I-T3) from the extracellular space into heart cells was measured relative to the extracellular space marker 3H-mannitol. The thyroid hormone maximal uptake was 54.4% for 125I-T4 and 52.15% for 125I-T3. The thyroid hormone net uptake was 25.69% for 125I-T4 and 25.49% for 125I-T3. Backflux from the intracellular space was 53.17% for 125I-T4 and 61.59% for 125I-T3. In the presence of unlabelled thyroid hormones, 125I-T4 and 125I-T3 maximal uptakes were reduced from 10.1 to 59.74% and from 34.6 to 65.3%, respectively, depending on the concentration of the unlabelled hormone, suggesting a saturable mechanism of the thyroid hormone uptake by the heart cells, with Km(T4)= 105.46 ,M and the maximal rate of 125I-thyroid hormone flux from the extracellular space to heart cells (Vmax(T4)) = 177.84 nM min,1 for 125I-T4 uptake, and Km(T3)= 80.0 ,M and Vmax(T3)= 118.5 nM min,1 for 125I-T3 uptake. [source] Modulation of sarcoplasmic reticulum Ca2+ -ATPase by chronic and acute exposure to peroxynitriteFEBS JOURNAL, Issue 13 2004Yolanda Gutiérrez-Martín The Ca2+ -ATPase of skeletal muscle sarcoplasmic reticulum (SERCA), an integral membrane protein, becomes irreversibly inactivated in vitro by the addition of a single bolus of peroxynitrite with a K0.5 of 200,300 µm, and this results in a large decrease of the ATP-dependent Ca2+ gradient across the sarcoplasmic reticulum (SR) membranes. The inactivation of SERCA is raised by treatment of SR vesicles with repetitive micromolar pulses of peroxynitrite. The inhibition of the SERCA is due to the oxidation of thiol groups and tyrosine nitration. Scavengers that react directly with peroxynitrite, such as cysteine, reduced glutathione, NADH, methionine, ascorbate or Trolox, a water-soluble analog of ,-tocopherol, afforded significant protection. However, dimethyl sulfoxide and mannitol, two hydroxyl radical scavengers, and ,-tocopherol did not protect SERCA from inactivation. Our results showed that the target of peroxynitrite is the cytosolic globular domain of the SERCA and that major skeletal muscle intracellular reductants (ascorbate, NADH and reduced glutathione) protected against inhibition of this ATPase by peroxynitrite. [source] The metabolic role and evolution of l -arabinitol 4-dehydrogenase of Hypocrea jecorinaFEBS JOURNAL, Issue 10 2004Manuela Pail l -Arabinitol 4-dehydrogenase (Lad1) of the cellulolytic and hemicellulolytic fungus Hypocrea jecorina (anamorph: Trichoderma reesei) has been implicated in the catabolism of l -arabinose, and genetic evidence also shows that it is involved in the catabolism of d -xylose in xylitol dehydrogenase (xdh1) mutants and of d -galactose in galactokinase (gal1) mutants of H. jecorina. In order to identify the substrate specificity of Lad1, we have recombinantly produced the enzyme in Escherichia coli and purified it to physical homogeneity. The resulting enzyme preparation catalyzed the oxidation of pentitols (l -arabinitol) and hexitols (d -allitol, d -sorbitol, l -iditol, l -mannitol) to the same corresponding ketoses as mammalian sorbitol dehydrogenase (SDH), albeit with different catalytic efficacies, showing highest kcat/Km for l -arabinitol. However, it oxidized galactitol and d -talitol at C4 exclusively, yielding l -xylo-3-hexulose and d -arabino-3-hexulose, respectively. Phylogenetic analysis of Lad1 showed that it is a member of a terminal clade of putative fungal arabinitol dehydrogenase orthologues which separated during evolution of SDHs. Juxtapositioning of the Lad1 3D structure over that of SDH revealed major amino acid exchanges at topologies flanking the binding pocket for d -sorbitol. A lad1 gene disruptant was almost unable to grow on l -arabinose, grew extremely weakly on l -arabinitol, d -talitol and galactitol, showed reduced growth on d -sorbitol and d -galactose and a slightly reduced growth on d -glucose. The weak growth on l -arabinitol was completely eliminated in a mutant in which the xdh1 gene had also been disrupted. These data show not only that Lad1 is indeed essential for the catabolism of l -arabinose, but also that it constitutes an essential step in the catabolism of several hexoses; this emphasizes the importance of such reductive pathways of catabolism in fungi. [source] Homocysteine-induced decrease in endothelin-1 production is initiated at the extracellular level and involves oxidative productsFEBS JOURNAL, Issue 20 2001Séverine Drunat The increased cardiovascular risk associated with hyperhomocysteinemia has been partly related to homocysteine (Hcy)-induced endothelial cell dysfunction. However, the intra or extracellular starting point of the interaction between Hcy and endothelial cells, leading to cellular dysfunction, has not yet been identified. We investigated the effects of both intracellular and extracellular Hcy accumulation on endothelin-1 (ET-1) synthesis by cultured human endothelial cells. Incubation of cultures with methionine (1.0 mmol·L,1) for 2 h induced a slight increase in cellular Hcy content but no change in ET-1 production. Incubation of cells with Hcy (0.2 mmol·L,1) led to a significant fall in ET-1 generation, accompanied by a significant increase in cellular Hcy content. Addition of the amino-acid transport system L substrate 2-amino-2-norbornane carboxylic acid had no effect on the Hcy-induced decrease in ET-1 production but significantly inhibited the Hcy-induced increase in the cellular Hcy content. Incubation of cells with a lower Hcy concentration (0.05 mmol·L,1) also reduced ET-1 production without increasing the cellular Hcy content. Co-incubation with extracellular free-radical inhibitors (superoxide dismutase, catalase and mannitol) markedly reduced the effect of Hcy on ET-1 production. Thus, it is extracellular Hcy accumulation that triggers the decrease in ET-1 production by endothelial cells through oxidative products. [source] Adhesion and development of the root rot fungus (Heterobasidion annosum) on conifer tissues: effects of spore and host surface constituentsFEMS MICROBIOLOGY ECOLOGY, Issue 2 2000Frederick O Asiegbu Abstract The objective of this study was to correlate the occurrence of particular root and woody stump surface components with the ability of spores of the root rot fungus (Heterobasidion annosum) to adhere, germinate and establish on conifer tissues. With the aid of high performance liquid chromatography, several sugars (pinitol, xylitol, dulcitol, mannitol, D -glucose, mannose, fructose) were detected on both stump and fine root surfaces of Scots pine and Norway spruce. Of all the sugars observed, xylose and arabinose were poorly utilized for initiation of germ tube growth whereas spore germination was enhanced in the presence of D -glucose, mannose or fructose. Oxidation of these sugars by pretreatment of wood discs or roots with periodic acid abolished the ability of the spores to germinate. Non-sugar components such as long chain fatty acids on spores and root surfaces as detected with nuclear magnetic resonance were found to have a significant influence on adhesion and initiation of germ tube development. Removal of these aliphatic compounds from the root surface increased spore germination by 2-fold, whereas similar treatment on spores led to a 5-fold decrease in adhesiveness to root material. In vitro studies revealed that the di-ethyl ether extract from the roots had no long term adverse effect on spore germination which suggests that the fungus may possess the capability to detoxify this substance. Similarly, adhesion of spores was affected by low and freezing temperatures. The role of significant levels of mannitol and trehalose accumulated in spores and hyphae of the fungi on viability, survival and tolerance to adverse conditions such as oxidative stress, freezing and desiccation are discussed. [source] The osmotic stress tolerance of basidiomycetous yeastsFEMS YEAST RESEARCH, Issue 4 2010Obakeng M. Tekolo Abstract The growth and accumulation of intracellular polyols at reduced water activity (aw) were studied in 40 basidiomycetous yeast strains. The growth of most strains showed greater tolerance to NaCl than sorbitol at the same aw. No strain was able to grow below 0.90aw. 13C nuclear magnetic resonance spectroscopy revealed that glycerol was the major solute accumulated intracellularly by all the yeasts when grown to 0.96aw (NaCl). Arabitol or mannitol was also accumulated in some yeasts, whereas a few only accumulated glycerol. Analysis of six yeasts in detail revealed that the intracellular glycerol concentrations of five yeasts increased significantly when grown at 0.96aw (NaCl or sorbitol) compared with growth at 0.998aw. Arabitol and mannitol concentrations also increased, but not to the same degree. Intracellular potassium concentrations decreased when grown at 0.96aw (NaCl or sorbitol) and sodium increased, but only when grown at 0.96aw (NaCl). The survival of nine strains was evaluated in soil cultures and it was found that all grew at 100% field capacity, whereas at lower field capacity, only some strains grew or survived. The growth of basidiomycetous yeasts appears to be more sensitive to reduced aw than ascomycetous yeasts. [source] Synthesis of Pederic Acid and Related Model StudiesHELVETICA CHIMICA ACTA, Issue 5 2004Steffen Breitfelder {[2-(Trimethylsilyl)ethoxy]methyl} (SEM)-protected pederic acid 16 was prepared by deriving the stereogenic center at C(7) from mannitol and those at C(2) and C(3) (mycalamide numbering) from trans -2,3-dimethyloxirane. Routes to pederamides involving a late oxygenation at C(7) were explored. [source] Ruthenium-Mediated Oxidation under Buffered Conditions: A Simple and Useful Protocol for the Synthesis of Norbornyl ,-Diketones with Acid Sensitive FunctionalitiesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2009Faiz Ahmed Khan Abstract The supported ruthenium-catalyzed oxidation of the 1,2-dihaloalkene moiety in tetrahalonorbornyl derivatives possessing acid labile functionalities to afford the corresponding ,-diketones is demonstrated. The protocol was successfully applied in the synthesis of a cyclopenta-annulated ,-lactone derived from D -mannitol. [source] | ||||||||||||||||||||||||||||||||||||||||