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Selected AbstractsShort-period hypoxia increases mouse embryonic stem cell proliferation through cooperation of arachidonic acid and PI3K/Akt signalling pathwaysCELL PROLIFERATION, Issue 2 2008S. H. Lee Hypoxia plays important roles in some early stages of mammalian embryonic development and in various physiological functions. This study examined the effect of arachidonic acid on short-period hypoxia-induced regulation of G1 phase cell-cycle progression and inter-relationships among possible signalling molecules in mouse embryonic stem cells. Hypoxia increased the level of hypoxia-inducible factor-1, (HIF-1,) expression and H2O2 generation in a time-dependent manner. In addition, hypoxia increased the levels of cell-cycle regulatory proteins (cyclin D1, cyclin E, cyclin-dependent kinase 2 (CDK2) and CDK4). Maximum increases in the level of these proteins and retinoblastoma phosphorylation were observed after 12,24 h of exposure to hypoxic conditions, and then decreased. Alternatively, the level of the CDK inhibitors, p21Cip1 and p27Kip1 were decreased. These results were consistent with the results of [3H]-thymidine incorporation and cell counting. Hypoxia also increased the level of [3H]-arachidonic acid release and inhibition of cPLA2 reduced hypoxia-induced increase in levels of the cell-cycle regulatory proteins and [3H]-thymidine incorporation. The level of cyclooxygenase-2 (COX-2) was also increased by hypoxia and inhibition of COX-2 decreased the levels of cell-cycle regulatory proteins and [3H]-thymidine incorporation. Indeed, the percentage of cells in S phase, levels of cell cycle regulatory proteins, and [3H]-thymidine incorporation were further increased in hypoxic conditions with arachidonic acid treatment compared to normoxic conditions. Hypoxia-induced Akt and mitogen-activated protein kinase (MAPK) phosphorylation was inhibited by vitamin C (antioxidant, 10,3 M). In addition, hypoxia-induced increase of cell-cycle regulatory protein expression and [3H]-thymidine incorporation were attenuated by LY294002 (PI3K inhibitor, 10,6 M), Akt inhibitor (10,6 M), rapamycin (mTOR inhibitor, 10,9 M), PD98059 (p44/42 inhibitor, 10,5 M), and SB203580 (p38 MAPK inhibitor, 10,6 M). Furthermore, hypoxia-induced increase of [3H]-arachidonic acid release was blocked by PD98059 or SB203580, but not by LY294002 or Akt inhibitor. In conclusion, arachidonic acid up-regulates short time-period hypoxia-induced G1 phase cyclins D1 and E, and CDK 2 and 4, in mouse embryonic stem cells through the cooperation of PI3K/Akt/mTOR, MAPK and cPLA2 -mediated signal pathways. [source] Evaluation of combined gene regulatory elements for transcriptional targeting of suicide gene expression to malignant melanomaEXPERIMENTAL DERMATOLOGY, Issue 6 2003Heike Rothfels Abstract:, Selective killing of tumors can be achieved by targeting the transcription of suicide genes via specific DNA control elements to malignant cells. Three different enhancer-promoter systems were constructed and evaluated for their capability to direct gene expression to melanoma. Two tissue-specific (tyrosinase and MIA) promoters and one weak viral promoter were fused to multiple tandem copies of a melanocyte-specific enhancer element. Reporter gene assays revealed a maximum increase in transcription by combining each promoter with 3,4 copies of the enhancer and demonstrated that all enhancer-promoter combinations exhibited tissue-specific activity. Though this activity was still significantly less than that of the strong but unspecific cytomegalo virus (CMV) promoter. In contrast, when these combinations were employed to drive the expression of two suicide genes, encoding the diphtheria toxin A chain (DT-A) and the prodrug-activating herpes simplex virus thymidine kinase (TK), respectively, only those constructs in which transcription was under the control of tissue-specific promoter elements mediated selective killing of melanoma cells. This killing was in the range of cell death induced by CMV promoter activity. Our data indicate that the enhancer/tyrosinase and enhancer/MIA promoter constructs but not the viral promoter constructs can provide a valuable tool for selective suicide gene expression in melanoma. [source] The use of indicator taxa as representatives of communities in bioassessmentFRESHWATER BIOLOGY, Issue 8 2005R. C. NIJBOER Summary 1. Sampling and processing of benthic macroinvertebrate samples is time consuming and expensive. Although a number of cost-cutting options exist, a frequently asked question is how representative a subset of data is of the whole community, in particular in areas where habitat diversity is high (like Dutch surface water habitats). 2. Weighted averaging was used to reassign 650 samples to a typology of 40 community types, testing the representativeness of different subsets of data: (i) four different types of data (presence/absence, raw, 2log- and ln-transformed abundance), (ii) three subsets of ,indicator' taxa (taxa with indicator weights 4,12, 7,12, and 10,12) and (iii) single taxonomic groups (n = 14) by determining the classification error. 3. 2log- and ln-transformed abundances resulted in the lowest classification error, whilst the use of qualitative data resulted in a reduction of 10% of the samples assigned to their original community type compared to the use of ln-transformed abundance data. 4. Samples from community types with a high number of unique indicator taxa had the lowest classification error, and classification error increased as similarity among community types increased. Using a subset of indicator taxa resulted in a maximum increase of the classification error of 15% when only taxa with an indicator weight 10,12 were included (error = 49.1%). 5. Use of single taxonomic groups resulted in high classification error, the lowest classification error was found using Trichoptera (68%), and was related to the frequency of the taxonomic group among samples and the indicator weights of the taxa. 6. Our findings that the use of qualitative data, subsets of indicator taxa or single taxonomic groups resulted in high classification error implies low taxonomic redundancy, and supports the use of all taxa in characterising a macroinvertebrate community, in particular in areas where habitat diversity is high. [source] Dietary cation,anion difference and cadmium concentration in grasses fertilized with chlorideGRASS & FORAGE SCIENCE, Issue 4 2007S. Pelletier Abstract High dietary cation,anion difference (DCAD) of grass herbage increases the occurrence of hypocalcaemia of dairy cows. Application of chloride fertilizer reduces DCAD of herbage but it could increase cadmium concentration in herbage. This study includes an experiment conducted in Australia and in Canada. A glasshouse experiment in Australia evaluated the effect of four rates of chloride application (0,240 kg ha,1) on values of herbage DCAD and cadmium concentration of above-ground plant material of timothy (Phleum pratense L.) and phalaris (Phalaris aquatica L.), harvested 6 weeks after sowing and grown on two soils that had received cadmium either as a contaminant in superphosphate (soil + Super) or in sewage biosolids (soil + Bio) along with respective control soils (soil 0 Super and soil 0 Bio). Application of chloride fertilizer decreased values of herbage DCAD by 349 mmolc kg,1 dry matter (DM). Herbage DCAD values were highest on the 0 Bio soil (739 mmolc kg,1 DM) and were not different among the three other soils. Species did not differ in herbage DCAD values. Cadmium concentration in the above-ground plant material was highest on the +Bio soil treatment (1·67 mg kg,1 DM) and was lower for the three other soil treatments. Above-ground plant material of phalaris had a higher cadmium concentration than that of timothy. Application of chloride fertilizer did not affect cadmium concentration in above-ground plant material, despite the high cadmium content of the soil on the +Bio treatment. The field experiment in Canada evaluated the effect of four rates of chloride application (0,144 kg ha,1) on cadmium concentration of a timothy-based grass sward grown on four sites with soils of different potassium content. Application of chloride fertilizer increased cadmium concentration of herbage at two of the four sites but the maximum increase in cadmium concentration was only 0·025 mg kg,1 DM. Chloride fertilizer can be applied to decrease forage DCAD with minimal risk of increasing Cd in the food chain. [source] Comparison of gingival blood flow during healing of simplified papilla preservation and modified Widman flap surgery: a clinical trial using laser Doppler flowmetryJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 10 2007M. Retzepi Abstract Aim: This prospective randomized-controlled clinical trial compared the gingival blood flow responses following simplified papilla preservation (test) versus modified Widman flap (control). Materials and Methods: Twenty contra-lateral upper sites with pocket depth 5 mm after initial treatment in 10 chronic periodontitis patients were randomly assigned to either test or control treatment, using a split-mouth design. Laser Doppler flowmetry recordings were performed pre-operatively, following anaesthesia, immediately post-operatively and on days 1, 2, 3, 4, 7, 15, 30 and 60, at nine selected sites per flap. Results: Significant ischaemia was observed at all sites following anaesthesia and immediately post-operatively. At the mucosal flap basis, a peak hyperaemic response was observed on day 1, which tended to resolve by day 4 at the test sites, but persisted until day 7 at the control sites. The buccal and palatal papillae blood perfusion presented the maximum increase on day 7 in both groups and returned to baseline by day 15. Both surgical modalities yielded significant pocket depth reduction, recession increase and clinical attachment gain. Conclusions: Periodontal access flaps represent an ischaemia,reperfusion flap model. The simplified papilla preservation flap may be associated with faster recovery of the gingival blood flow post-operatively compared with the modified Widman flap. [source] Transport of levovirin prodrugs in the human intestinal Caco-2 cell lineJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 6 2006Fujun Li Abstract The transport of 10 amino acid ester prodrugs of levovirin (LVV) was investigated in the human intestinal Caco-2 cell line in order to overcome the poor oral bioavailability of LVV, an investigational drug for the treatment of hepatitis C infection. The prodrugs were designed to improve the permeability of LVV across the intestinal epithelium by targeting the di/tri-peptide carrier, PepT1. Caco-2 cell monolayers were employed to study the transport and hydrolysis properties of the prodrugs. Among all mono amino acid ester prodrugs studied, the LVV-5,-(L)-valine prodrug (R1518) exhibited the maximum increase (48-fold) in permeability with nearly complete conversion to LVV within 1 h. Di-amino acid esters did not offer significant enhancement in permeability comparing with mono amino acid esters and exhibited slower conversion to LVV in Caco2 cell monolayers. Pharmacokinetic screening studies of the prodrugs in rats yielded the highest fold increase (6.9-fold) of AUC with R1518 and in general displayed a similar trend to that observed in increases of permeability in Caco-2 cells. Mechanisms involved in the Caco-2 cell transport of R1518 were also investigated. Results of bi-directional transport studies support the involvement of carrier-mediated transport mechanisms for R1518, but not for the LVV-5,-(D)-valine prodrug or LVV. Moreover, the permeability of R1518 was found to be proton dependent. PepT1-mediated transport of R1518 was supported by results of competitive transport studies of R1518 with the PepT1 substrates enalapril, Gly-Sar, valganciclovir, and cephalexin. R1518 was also found to inhibit the permeability of valganciclovir and cephalexin. These results suggest that R1518 is a PepT1 substrate as well as an inhibitor. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:1318,1325, 2006 [source] Properties of covalently bonded layered-silicate/polystyrene nanocomposites synthesized via atom transfer radical polymerizationJOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 3 2005Chung-Ping Li Abstract Covalently bonded layered silicated/polystyrene nanocomposites were synthesized via atom transfer radical polymerization in the presence of initiator-modified layered silicate. The resulting nanocomposites had an intercalated and partially exfoliated structure, as confirmed by X-ray diffraction and transmission electron microscopy. The thermal properties of the nanocomposites improved substantially over those of neat polystyrene. In particular, a maximum increase of 35.5 °C in the degradation temperature was displayed by these nanocomposites. Additionally, the surface elastic modulus and hardness of these nanocomposites were more than double those of pure polystyrene. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 534,542, 2005 [source] Evaluation of phytoconstituents of Terminalia arjuna for wound healing activity in ratsPHYTOTHERAPY RESEARCH, Issue 9 2006Minakshi Chaudhari Abstract The effect of topical application of phytoconstituents (fraction I, II and III) fractionated from a hydroalcohol extract of the bark of the plant, Terminalia arjuna, was assessed on the healing of rat dermal wounds using in vivo models. The results indicated a statistically significant increase in the tensile strength of the incision wounds and the percent epithelialization of excision wounds compared with control (p < 0.05). However, topical treatment with fraction I, consisting mainly of tannins, was found to demonstrate a maximum increase in the tensile strength of incision wounds. Even with respect to excision wounds, the fastest rate of epithelialization was seen with fraction I. Hexosamine estimation of granulation tissue obtained from excision wounds revealed an increase in the hexosamine content with fraction I compared with the control. In addition, fraction I from the hydroalcohol extract of Arjuna bark possessed antimicrobial activity against tested microorganisms such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, Streptococcus pyogenes but not Candida albicans. These results strongly document the beneficial effects of fraction I, consisting mainly of tannins, of Terminalia arjuna in the acceleration of the healing process. Thus, the present study validates the claim made with respect to the plant as well as corroborating the astringent effect of tannins by drawing the tissues closer together. Copyright © 2006 John Wiley & Sons, Ltd. [source] Effects of dietary glucose level during late gestation on litter performance and glucose concentration in sowsANIMAL SCIENCE JOURNAL, Issue 1 2009Young-Keun HAN ABSTRACT The effects of feeding glucose during the 5 days before parturition on litter performance and on glucose concentration in sows were studied. At day 100 of gestation, 130 multiparous sows were assigned to the treatments. Late gestating sows were fed 0 g, 150 g, 250 g, 350 g and 450 g of glucose a day, respectively. During lactation, all sows were given free access to the same lactation diet (without glucose). One day before parturition, blood samples were collected from 30 sows (6 sows per treatment) at 10 before and 20, 40, 60 and 80 min after the meal. The supply of additional dietary glucose increased piglet birth weight (P < 0.05). Feed intake in week 1 and week 1,4 of lactation was greatest in sows fed the 0% glucose diet, least by sows fed the 18% glucose diet, and intermediate by sows fed the 6, 10, 14% glucose diets (P < 0.05). Basal glucose concentration and time of maximum glucose concentration after glucose intake were not affected by dietary treatment in the last 5 days of gestation. The sows fed the 14 and 18% glucose diets had greater maximum increase in glucose concentration than sows fed diet without glucose (P < 0.05). In conclusion, feeding glucose to sows during 5 days before parturition increased birth weight of live-born piglet and decreased sows feed intake during lactation, but did not affect the performance of sows and piglets. [source] Effect of carbon source addition on toluene biodegradation by an Escherichia coli DH5, transconjugant harboring the TOL plasmidBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Kaoru Ikuma Abstract Horizontal gene transfer (HGT) of plasmids is a naturally occurring phenomenon which could be manipulated for bioremediation applications. Specifically, HGT may prove useful to enhance bioremediation through genetic bioaugmentation. However, because the transfer of a plasmid between donor and recipient cells does not always result in useful functional phenotypes, the conditions under which HGT events result in enhanced degradative capabilities must first be elucidated. The objective of this study was to determine if the addition of alternate carbon substrates could improve toluene degradation in Escherichia coli DH5, transconjugants. The addition of glucose (0.5,5,g/L) and Luria,Bertani (LB) broth (10,100%) resulted in enhanced toluene degradation. On average, the toluene degradation rate increased 14.1 (±2.1)-fold in the presence of glucose while the maximum increase was 18.4 (±1.7)-fold in the presence of 25% LB broth. Gene expression of xyl genes was upregulated in the presence of glucose but not LB broth, which implies different inducing mechanisms by the two types of alternate carbon source. The increased toluene degradation by the addition of glucose or LB broth was persistent over the short-term, suggesting the pulse amendment of an alternative carbon source may be helpful in bioremediation. While the effects of recipient genome GC content and other conditions must still be examined, our results suggest that changes in environmental conditions such as alternate substrate availability may significantly improve the functionality of the transferred phenotypes in HGT and therefore may be an important parameter for genetic bioaugmentation optimization. Biotechnol. Bioeng. 2010;107: 269,277. © 2010 Wiley Periodicals, Inc. [source] Alkaloid production in Vernonia cinerea: Callus, cell suspension and root culturesBIOTECHNOLOGY JOURNAL, Issue 8 2007Priti Maheshwari Abstract Fast-growing callus, cell suspension and root cultures of Vernonia cinerea, a medicinal plant, were analyzed for the presence of alkaloids. Callus and root cultures were established from young leaf explants in Murashige and Skoog (MS) basal media supplemented with combinations of auxins and cytokinins, whereas cell suspension cultures were established from callus cultures. Maximum biomass of callus, cell suspension and root cultures were obtained in the medium supplemented with 1 mg/L ,-naphthaleneacetic acid (NAA) and 5 mg/L benzylaminopurine (BA), 1.0 mg/L NAA and 0.1 mg/L BA and 1.5 mg/L NAA, respectively. The 5-week-old callus cultures resulted in maximum biomass and alkaloid contents (750 ,g/g). Cell suspension growth and alkaloid contents were maximal in 20-day-old cultures and alkaloid contents were 1.15 mg/g. A 0.2-g sample of root tissue regenerated in semi-solid medium upon transfer to liquid MS medium containing 1.5 mg/L NAA regenerated a maximum increase in biomass of 6.3-fold over a period of 5 weeks. The highest root growth and alkaloid contents of 2 mg/g dry weight were obtained in 5-week-old cultures. Maximum alkaloid contents were obtained in root cultures in vitro compared to all others including the alkaloid content of in vivo obtained with aerial parts and roots (800 ,g/g and 1.2 mg/g dry weight, respectively) of V. cinerea. [source] Spinal amino acid release and repeated withdrawal in spinal morphine tolerant ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2003Takae Ibuki We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol ,l,1 h,1) or saline (IT-S: 1 ,l h,1) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg,1) or saline (IP-S: 3 ml kg,1) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine+IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine+i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. For the IT-M+IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance. British Journal of Pharmacology (2003) 138, 689,697. doi:10.1038/sj.bjp.0705102 [source] Biphasic effects of NMDA on the motility of the rat portal veinBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2000Z L Rossetti The effect of NMDA on the motility of the rat portal vein was studied in an isolated preparation. NMDA induced a concentration-dependent (10,7,10,4 M) increase of the contraction frequency (maximum increase, 148±6% of control at NMDA 10,4 M). The NMDA-induced excitatory response was prevented by the competitive NMDA receptor antagonists (±)-2-Amino-5-phosphonopentanoic acid (AP-5, 5×10,4 M) or (RS)-3-(2-carboxypiperazine-4-yl) propyl-1-phosphonic acid (CPP, 10,4 M). Tetrodotoxin (TTX, 10,6 M) or atropine (10,4 M) abolished the NMDA-induced increase of the portal vein motility and reversed the excitatory effect to a concentration-dependent inhibition (maximum inhibition, 52±8 and 29±7% of controls, respectively, at NMDA 10,3 M). Removal of the endothelium abolished the NMDA-induced inhibitory response. Sodium nitroprusside concentration-dependently (10,7,10,5 M) inhibited the portal vein motility, while L -NG -nitro-arginine methyl ester (L -NAME, 10,4 M) reversed the inhibitory effect of NMDA (in the presence of TTX), restoring the portal vein spontaneous activity to control values. These results show that NMDA modulates the portal vein motility in a biphasic manner: via indirect activation, through prejunctional NMDA receptors presumably located on intrinsic excitatory neuronal afferences, or via direct inhibition, through endothelial NMDA receptors activating the nitric oxide pathway. Overall these findings support the hypothesis of the existence of a peripheral glutamatergic innervation modulating the contractile activity of the rat portal vein. British Journal of Pharmacology (2000) 129, 156,162; doi:10.1038/sj.bjp.0703002 [source] Effects of higher-order wavefront aberrations on the eye's depth of focusACTA OPHTHALMOLOGICA, Issue 2008N CHATEAU Purpose To evaluate the impact of higher order aberrations (HOA), defined by individual Zernike polynomial coefficients, on the eye's depth of focus using an adaptive optics (AO) system. Methods A crx1 AO visual simulator (Imagine Eyes, France) was used to introduce different amounts of individual 3rd and 4th order HOA in 10 healthy eyes. These HOA included coma (Z(3,-1)) and trefoil (Z(3,-3)) at magnitudes of +/-0.3 µm, and spherical aberration (SA) (Z(4,0)) at magnitudes of +/-0.3,+/-0.6 and +/-0.9 µm through a fixed 6-mm pupil diameter. A through-focus response (TFR) curve was assessed by recording the percentage of optotype letters of fixed 20/50 size that the subject could identify while these letters were presented at various target distances. Testing was performed under cycloplegia. For each applied HOA, the subject's depth of focus (DoF) and center of focus (CoF) were computed as, respectively, the half-maximum width and the midpoint of the TFR curve. Results The introduction of SA resulted in linearly shifting the CoF by 1.3 D for each 0.5 µm of wavefront. The shift was hyperopic with positive SA, myopic with negative SA. The simulation of either positive or negative SA also had the effect of enhancing the DoF, up to a maximum increase of 2 D with 0.6 µm of SA. The enhancement became smaller when the SA was further increased. Trefoil and coma appeared to neither shift the CoF nor significantly modify the DoF. Conclusion AO technology allowed us to selectively test the visual impact of several HOA on the DoF. The introduction of SA significantly shifted and expanded the subjects' overall DoF. This technique could help in designing optimal corrections for presbyopia and allowing patients to preview refractive surgery outcomes. Commercial interest [source] Effect of First Treatment with Aminobisphosphonates Pamidronate and Ibandronate on Circulating Lymphocyte SubpopulationsJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2000Martin Pecherstorfer Abstract Up to 60% of patients receiving their first infusion of the bisphosphonate pamidronate experience an acute-phase reaction. In this study, we used flow cytometry to determine the effects of pamidronate treatment on circulating lymphocyte subpopulations, and we investigated whether pamidronate and ibandronate treatment affect lymphocyte subpopulations differently. Twenty patients received a pamidronate infusion, 20 patients received intravenously injected ibandronate, and 10 controls received a clodronate infusion. Pamidronate treatment was followed by a significant increase in median body temperature at the 10-hour measurement and a significant decrease in counts of circulating lymphocytes, natural killer cells, T cells, and CD4+ and CD8+ T-cell subsets. Ibandronate treatment did not affect median body temperature, and it was associated at the 10-hour measurement with maximum increases in total lymphocyte count, B cells, T cells, and CD4+ and CD8+ T-cell subsets. Thus, there is a substantial difference in the hematologic response to initial treatments with pamidronate and ibandronate. Clodronate treatment did not induce changes in body temperature or significantly affect the number of circulating T cells and NK cells. The reduction in lymphocyte subsets after initial pamidronate therapy might be mediated by the release of tumor necrosis factor ,, whose source in the acute-phase reaction could be T cells. [source] Endogenous melatonin protects L -DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L -DOPA therapy in Parkinson's diseaseJOURNAL OF PINEAL RESEARCH, Issue 3 2006Gaia Rocchitta Abstract:, We previously showed, using microdialysis, that autoxidation of exogenous L-dihydroxyphenylalanine (l -DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l -DOPA semiquinone (l -DOPA-SQ). In the present study, intrastriatal infusion of l -DOPA (1.0 ,m for 200 min) increased dialysate l -DOPA concentrations (maximum increases up to 116-fold baseline values); moreover, l -DOPA-SQ was detected in dialysates. Individual dialysate concentrations of l -DOPA were negatively correlated with those of l -DOPA-SQ. Co-infusion of N -acetylcysteine (100 ,m) or melatonin (50 ,m) increased l -DOPA (up to 151- and 246-fold, respectively) and decreased l -DOPA-SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l -DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12-h interval] significantly increased striatal baseline dialysate concentrations of l -DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l -DOPA, l -DOPA-SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24-h light cycle for 1 wk. In melatonin-depleted rats, systemic l -DOPA induced a smaller increase in dialysate l -DOPA, a greater increase in l -DOPA-SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co-administration of melatonin (5.0 mg/kg, i.p., twice in a 12-h interval) with l -DOPA, in control as well as in light-exposed rats, significantly increased dialysate l -DOPA concentrations, greatly inhibited l -DOPA-SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l -DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with l -DOPA markedly increases striatal l -DOPA bioavailability in control as well as in melatonin-depleted rats. These results may be of relevance to the long-term l -DOPA therapy of Parkinson's disease. [source] Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs,JOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2009A. A. MAIANTE The effects of methadone and morphine were compared in conscious dogs. Six animals received morphine sulfate (1 mg/kg) or methadone hydrochloride (0.5 mg/kg [MET0.5] or 1.0 mg/kg [MET1.0]) intravenously (i.v.) in a randomized complete block design. Cardiopulmonary variables were recorded before (baseline), and for 120 min after drug administration. One outlier was not included in the statistical analysis for hemodynamic data. Morphine decreased heart rate (HR) compared to baseline from 30 to 120 min (,15% to ,26%), while cardiac index (CI) was reduced only at 120 min (,19%). Greater and more prolonged reductions in HR (,32% to ,46%) and in CI (,24% to ,52%) were observed after MET1.0, while intermediate reductions were recorded after MET0.5 (,19 to ,28% for HR and ,17% to ,27% for CI). The systemic vascular resistance index (SVRI) was increased after methadone; MET1.0 produced higher SVRI values than MET0.5 (maximum increases: 57% and 165% for MET0.5 and MET1.0, respectively). Compared to morphine, oxygen partial pressure (PaO2) was lower (,12% to ,13%) at 5 min of methadone (0.5 and 1.0 mg/kg), while carbon dioxide partial pressure (PaCO2) did not change significantly. It was concluded that methadone induces cardiovascular changes that are dose-related and is a more potent cardiovascular depressant agent than morphine in conscious dogs. [source] TIMBER MARKETS AND FUEL TREATMENTS IN THE WESTERN U.S.NATURAL RESOURCE MODELING, Issue 1 2006KAREN L. ABT ABSTRACT. We developed a model of interrelated timber markets in the U.S. West to assess the impacts of large-scale fuel reduction programs on these markets, and concomitant effects ofthe market on the fuel reduction programs. The linear programming spatial equilibrium model allows interstate and international trade with western Canada and the rest of the world, while accounting for price effects of introducing softwood logs to the market. The model maximizes area treated, given fire regime-condition class priorities, maximum increases in softwood processing capacity, maximum rates of annual treatments, prohibitions on exports of U.S. and Canadian softwood logs from public lands and a fixed annual treatment budget. Results show that the loss to U.S. private timber producers is less than the gains for timber consumers (mills). States receiving more treatments when spending is not constrained by state proportions include Idaho, Montana, New Mexico and Oregon. When only the wildland-urban interface is treated, California, Oregon and Washington receive more treatments. Utah and Colorado receive more treatments when low risk stands are included. [source] | |||||||||||||