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711.
Herrera-Ruiz M González-Carranza A Zamilpa A Jiménez-Ferrer E Huerta-Reyes M Navarro-García VM 《Journal of ethnopharmacology》2011,138(2):261-267
Ethnopharmacological relevance
Loeselia mexicana (Lam.) Brand has been used in Mexican Traditional Medicine to treat “espanto” or “susto” (fear), which is a culturally affiliated syndrome whose symptomatology comprises loss of appetite, difficulty in sleeping, and also nausea and fatigue, with a sensation of fear or risk - real or imagined - to external stimuli.Aim of the study
The anxiolytic effect of the standardized methanol extract of Loeselia mexicana, with regard to its content of coumarin daphnoretin, was researched utilizing the elevated plus maze (EPM) in order to demonstrate whether the biological effect produced by the plant is antagonized by drugs that block γ-amino butyric acid (GABA)ergic transmission.Materials and methods
The methanolic extract of Loeselia mexicana (LmMeOH) was tested at different doses on the EPM and then the interaction of this extract was evaluated in the same model with different GABAergic drugs, such as flumazenil (FLU) 10 mg/kg, bicuculline (BIC) 5 mg/kg, pentylenetetrazole (PTZ) 10 mg/kg, and picrotoxin (PTX) 2 mg/kg. The effect of all of these treatments was evaluated by means of the open field test (OFT). Coumarin content was measured by the high performance liquid chromatography (HPLC) technique.Results
The 200- and 400-mg/kg doses of methanolic extract containing 3.14 and 6.28 mg of daphnoretin, respectively, induced an anxiolytic effect in the EPM without modification of the spontaneous motor activity. The anxiolytic activity of 200 mg/kg of methanolic extract in EPM-exposed mice was antagonized by PTX, BIC, and FLU, but not by PTZ.Conclusion
The data presented here indicate that the Loeselia mexicana Brand methanolic extract possesses a significant anxiolytic effect that appears to be mediated in part by activation of the GABAergic system. 相似文献712.
713.
Gomes Villarinho J Fachinetto R de Vargas Pinheiro F da Silva Sant'Anna G Machado P Dombrowski PA da Cunha C de Almeida Cabrini D Pinto Martins MA Gauze Bonacorso H Zanatta N Antonello Rubin M Ferreira J 《Progress in neuro-psychopharmacology & biological psychiatry》2012,39(1):31-39
Monoamine oxidase (MAO) inhibitors were the first antidepressant drugs to be prescribed and are still used today with great success, especially in patients resistant to other antidepressants. In this study, we evaluated the MAO inhibitory properties and the potential antidepressant action of 2-(3,4-dimethoxy-phenyl)-4,5-dihydro-1H-imidazole (2-DMPI) in mice. We found that 2-DMPI inhibited both MAO isoforms (K(i) values were 1.53 (1.3-1.8) μM and 46.67 (31.8-68.4) μM for MAO-A and MAO-B, respectively) with 30-fold higher selectivity toward MAO-A. In relation to the nature of MAO-A inhibition, 2-DMPI showed to be a mixed and reversible inhibitor. The treatment with 2-DMPI (100-1000 μmol/kg, s.c.) caused a significant decrease in immobility time in the tail suspension test (TST) without affecting locomotor activity, motor coordination or anxiety-related activities. Conversely, moclobemide (1000 μmol/kg, s.c.) caused a significant increase in immobility time in the TST, which appeared to be mediated by a nonspecific effect on motor coordination function. 2-DMPI (300 μmol/kg, s.c.) decreased serotonin turnover in the cerebral cortex, hippocampus and striatum, whereas dopamine turnover was diminished only in the striatum, and norepinephrine turnover was not changed. The antidepressant-like effect of 2-DMPI was inhibited by the pretreatment of mice with methysergide (2 mg/kg, s.c., a non-selective serotonin receptor antagonist), WAY100635 (0.1 mg/kg, s.c., a selective 5-HT(1A) receptor antagonist) or haloperidol (0.05 mg/kg, i.p., a non-selective dopamine receptor antagonist). These results suggest that 2-DMPI is a prototype reversible and preferential MAO-A inhibitor with potential antidepressant activity, due to its modulatory effect on serotonergic and dopaminergic systems. 相似文献
714.
Naspolini AP Cocco AR Villa Martignoni F Oliveira MS Furian AF Rambo LM Rubin MA Barron S Mello CF 《Epilepsy research》2012,100(1-2):12-19
Polyamines, including spermidine, facilitate seizures by positively modulating N-methyl-d-aspartate receptors (NMDAr). Although NMDAr antagonists decrease seizures, it remains to be determined whether traxoprodil, a selective antagonist at the NR2B subunit of the NMDAr, decreases seizures and whether spermidine facilitates pentylenetetrazol (PTZ)-induced seizures. Adult male Wistar rats were injected in the lateral ventricle with 0.9% NaCl (1μl, i.c.v.), spermidine (0.02, 0.2 or 2nmol/site, i.c.v.) or traxoprodil (0.2, 2 or 20nmol, i.c.v.) and with PTZ (35 or 70mg/kg, i.p.). The effect of orally administered traxoprodil (60mg/kg, p.o.) on seizures was also investigated. Latencies to clonic and generalized seizures, as well the total time spent in seizures were recorded by behavioral and electrographic methods (EEG). Spermidine (2nmol/site; i.c.v.) facilitated the seizures induced by a sub-threshold dose of PTZ (35mg/kg; i.p.), but did not alter seizure activity induced by a convulsant dose of PTZ (70mg/kg; i.p.). Traxoprodil (20nmol i.c.v.) increased the latency to generalized tonic-clonic seizures induced by PTZ (70mg/kg; i.p.). Traxoprodil (60mg/kg, p.o.) increased the latency to clonic and generalized seizures, and decreased the total time spent in seizures. These results support the role for the NR2B subunit in PTZ-induced seizures. 相似文献
715.
Saile E Boons GJ Buskas T Carlson RW Kannenberg EL Barr JR Boyer AE Gallegos-Candela M Quinn CP 《Clinical and Vaccine Immunology : CVI》2011,18(5):743-748
The Bacillus anthracis exosporium protein BclA contains an O-linked antigenic tetrasaccharide whose terminal sugar is known as anthrose (J. M. Daubenspeck et al., J. Biol. Chem. 279:30945-30953, 2004). We hypothesized that serologic responses to anthrose may have diagnostic value in confirming exposure to aerosolized B. anthracis. We evaluated the serologic responses to a synthetic anthrose-containing trisaccharide (ATS) in a group of five rhesus macaques that survived inhalation anthrax following exposure to B. anthracis Ames spores. Two of five animals (RM2 and RM3) were treated with ciprofloxacin starting at 48 hours postexposure and two (RM4 and RM5) at 72 h postexposure; one animal (RM1) was untreated. Infection was confirmed by blood culture and detection of anthrax toxin lethal factor (LF) in plasma. Anti-ATS IgG responses were determined at 14, 21, 28, and 35 days postexposure, with preexposure serum as a control. All animals, irrespective of ciprofloxacin treatment, mounted a specific, measurable anti-ATS IgG response. The earliest detectable responses were on days 14 (RM1, RM2, and RM5), 21 (RM4), and 28 (RM3). Specificity of the anti-ATS responses was demonstrated by competitive-inhibition enzyme immunoassay (CIEIA), in which a 2-fold (wt/wt) excess of carbohydrate in a bovine serum albumin (BSA) conjugate of the oligosaccharide (ATS-BSA) effected >94% inhibition, whereas a structural analog lacking the 3-hydroxy-3-methyl-butyryl moiety at the C-4" of the anthrosyl residue had no inhibition activity. These data suggest that anti-ATS antibody responses may be used to identify aerosol exposure to B. anthracis spores. The anti-ATS antibody responses were detectable during administration of ciprofloxacin. 相似文献
716.
Lopez-Vilchez I Hedner U Altisent C Diaz-Ricart M Escolar G Galan AM 《The American journal of pathology》2011,178(6):2938-2948
Clinical evidence accumulated from hemophilic patients during prophylaxis with recombinant activated factor VII (rFVIIa) suggests that the duration of the hemostatic action of rFVIIa exceeds its predicted plasma half-life. Mechanisms involved in this outcome have not been elucidated. We have investigated in vitro the redistribution of rFVIIa in platelets from healthy donors, patients with FVII deficiency, and one patient with Bernard-Soulier syndrome. Platelet-rich plasma was exposed to rFVIIa (3 to 60 μg/mL). Flow cytometry, immunocytochemistry, and coagulation tests were applied to detect and quantify rFVIIa. The hemostatic effect of rFVIIa associated to platelets was evaluated using perfusion models. Our studies revealed a dose-dependent association of rFVIIa to the platelet cytoplasm with redistribution into the open canalicular system, and α granules. Mechanisms implicated in the internalization are multiple, involve GPIb and GPIV, and require phospholipids and cytoskeletal assembly. After platelet activation with thrombin, platelets exposed rFVIIa on their membrane. Perfusion studies revealed that the presence of 30% of platelets containing FVIIa improved platelet aggregate formation and enhanced fibrin generation (P < 0.01 versus control). Our results indicate that, at therapeutic concentrations, rFVIIa can be internalized into platelets, where it is protected from physiological clearance mechanisms and can still promote hemostatic activity. Redistribution of rFVIIa into platelets may explain the prolonged prophylactic effectiveness of rFVIIa in hemophilia. 相似文献
717.
Serum matrix metalloproteinase 7 levels identifies poor prognosis advanced colorectal cancer patients 总被引:3,自引:0,他引:3
Maurel J Nadal C Garcia-Albeniz X Gallego R Carcereny E Almendro V Mármol M Gallardo E Maria Augé J Longarón R Martínez-Fernandez A Molina R Castells A Gascón P 《International journal of cancer. Journal international du cancer》2007,121(5):1066-1071
Metalloproteinase 7 (MMP-7) plays an important role in tumor growth, invasion and dissemination, and is secreted to the media. Because of the close implication of MMP-7 in cancer biology, we sought to define the prognostic significance of serum levels of MMP-7 in metastatic colorectal cancer (CRC) and explore its possible impact in the daily clinical practice. MMP-7 expression was determined by enzyme-linked immunoabsorbent assay. We assessed serum MMP-7 levels in 87 healthy controls, 96 patients with nonmetastatic CRC and 120 patients with advanced CRC. Clinical information was gathered from patient files. Cox proportional hazards model was used to assess survival. MMP-7 and the variables associated with prognosis were entered and a backward elimination method was employed to adjust the model. Inclusion criteria was p = 0.05 and exclusion criteria was p >/= 0.10. Advanced CRC patients have a significant higher mean serum MMP-7 levels (13.4 ng/ml) than those in nonmetastatic CRC (5.5 ng/ml; p < 0.001) and healthy controls (4.2 ng/ml; p < 0.001). In metastatic patients, after adjusting for other prognostic variables, MMP-7 (entered as a continuous variable) is associated with decreased survival (HR 1.016, IC 95% 1.002-1.031). Serum MMP-7 levels are significantly elevated in patients with advanced CRC. In conclusion, MMP-7 is an independent prognostic factor for survival in advanced CRC. In our sample, the risk of death associated to MMP-7 increase is much higher than the risk of death associated to lactate dehydrogenase elevation. 相似文献
718.
719.
Tissue factor (TF) has been found associated with platelets. Mechanisms responsible for TF-platelet interactions and transport are not fully understood. We explored the response of isolated washed platelets to preparations of recombinant (rTF) or placental (pTF) human TF, exposed on lipid microvesicles (MVs). Sequential ultrastructural and immunocytochemical studies revealed trafficking of these TF preparations, being endocytosed by platelets into channels of the open canalicular system (OCS) and accumulating in the cytoplasm and occasionally in alpha-granules. The process of internalization of TF-MVs was accomplished in less than 30 min, being faster for the placental (pTF) than for the recombinant (rTF) preparation. Signs of mild platelet activation with pseudopodia formation were observed at early stages of internalization. Platelets returned to an apparent resting state after 5-10 min. All of these observations paralleled with modifications on patterns of tyrosine phosphorylation for several signaling proteins. Our studies demonstrate that platelets possess mechanisms to capture and incorporate TF-rich vesicles. These processes were accelerated by the presence of other contaminating cellular antigens in the vesicles (pTF). TF carried by platelets could play a potential role in platelet thrombus formation and by extension in the development of ischemic complications. 相似文献
720.
Diaz-Ricart M Palomo M Fuste B Lopez-Vilchez I Carbo C Perez-Pujol S White JG Escolar G 《Thrombosis research》2008,121(6):873-883