Home About us Contact
|
Home About us Contact | ||
|
|
||
Complete Protection (complete + protection)
Selected AbstractsSeizure Suppression by Adenosine-releasing Cells Is Independent of Seizure FrequencyEPILEPSIA, Issue 8 2002Detlev Boison Summary: ,Purpose: Intraventricular cellular delivery of adenosine was recently shown to be transiently efficient in the suppression of seizure activity in the rat kindling model of epilepsy. We tested whether the suppression of seizures by adenosine-releasing grafts was independent of seizure frequency. Methods: Adenosine-releasing cells were encapsulated and grafted into the lateral brain ventricle of rats kindled in the hippocampus. During 4 weeks after grafting, electric test stimulations were delivered at a frequency of either once a week or 3 times per week. Seizure activity was evaluated by visual scoring of seizure severity and by the recording of EEGs. Results: Adenosine released from encapsulated cells exerted potent antiepileptic activity for ,2 weeks. One week after grafting, treated rats displayed a complete protection from clonic seizures, and a protection from focal seizures was observed in the majority of animals. Seizure suppression was accompanied by a reduction of afterdischarges in EEG recordings. The protective efficacy of the grafted cells was the same irrespective of whether electrical test stimulations were delivered 1 or 3 times per week. Rats receiving control grafts continued to display full clonic convulsions. Conclusions: This study demonstrated that the frequency of test stimulations did not influence the seizure-suppressive potential of adenosine-releasing grafts. Thus the local delivery of adenosine is likely to be effective in seizure control over a threefold range of seizure-discharge frequency. [source] Mediastinal lymph node CD8,, DC initiate antigen presentation following intranasal coadministration of ,-GalCerEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 8 2007Sung-Youl Ko Abstract Our previous study revealed that ,-galactosylceramide (,-GalCer) is a potent nasal vaccine adjuvant inducing both potent humoral and cellular immune responses and affording complete protection against viral infections and tumors. However, the antigen-presenting cells (APC) that are activated by NKT cells and thereby initiate the immune responses following intranasal coadministration of protein antigen and ,-GalCer are poorly understood. We assessed here where antigen presentation occurs and which APC subset mediates the early stages of immune responses when protein antigen and ,-GalCer are intranasally administered. We show that dendritic cells (DC), but not B cells, initiated the mucosal immune responses at mediastinal lymph nodes. Of the DC subsets, the CD8,,B220,CD11c+ DC subset played the most prominent role in the direct and cross-presentation of protein antigen to naive T cells and in triggering the naive T cells to differentiate into effector T cells. This might be mainly caused by a relatively larger population of CD1dhigh cells of CD8,,B220,CD11c+ DC subset than those of other DC subsets. These results indicate that CD8,,B220,CD11c+ DC is the principal subset becoming immunogenic after interaction with NKT cells and abrogating tolerance to intranasally administered protein antigen when ,-GalCer is coadministered as a nasal vaccine adjuvant. [source] Relationship between stump treatment coverage using the biological control product PG Suspension, and control of Heterobasidion annosum on Corsican pine, Pinus nigra ssp. laricioFOREST PATHOLOGY, Issue 1 2008K. V. Tubby Summary The relationship between the proportion of the stump surface covered by the biological stump treatment agent PG Suspension, containing Phlebiopsis gigantea and its efficacy against the pathogen Heterobasidion annosum sensu stricto was studied during a first thinning of Corsican pine (Pinus nigra ssp. laricio) in Thetford Forest, UK. PG Suspension was manually applied to 100%, 75%, 50% or 0% of the surface of 150 stumps. Spores of H. annosum were inoculated onto 75 of the stumps, and the remaining stumps exposed to natural airborne spore deposition. The relationship between coverage and efficacy was found to be quantitative. Covering all the stump surface with PG Suspension completely excluded the pathogen, whereas stumps not treated with PG Suspension (the 0% treatment) became infected with H. annosum. Partial (75%) PG Suspension coverage resulted in the pathogen colonizing 40% of stumps following artificial inoculation with H. annosum, and just 7% of stumps exposed to ambient H. annosum spore infection. Decreasing levels of coverage allowed increasing areas of the stump surface to be colonized by H. annosum. Some small gaps in coverage were closed by lateral growth of P. gigantea, but it is recommended that operators aim for full stump coverage to give complete protection against H. annosum. [source] Characterization of serum and mucosal antibody responses and relative per cent survival in rainbow trout, Oncorhynchus mykiss (Walbaum), following immunization and challenge with Flavobacterium psychrophilumJOURNAL OF FISH DISEASES, Issue 12 2002B R LaFrentz Abstract Serum and mucosal antibody responses of juvenile rainbow trout, Oncorhynchus mykiss, were characterized by enzyme-linked immunosorbent assay (ELISA) following immunization with various preparations of formalin-killed Flavobacterium psychrophilum cells. The protective nature of these preparations was then determined by immunizing rainbow trout fry and challenging with the bacterium. Juvenile rainbow trout immunized intraperitoneally (i.p.) with formalin-killed F. psychrophilum emulsified with Freund's complete adjuvant (FCA), and i.p. with formalin-killed F. psychrophilum either with or without culture supernatant generated significant serum antibody responses by 6 and 9 weeks, respectively. Significant mucosal antibody responses were detected by 9 weeks only in fish immunized i.p. with killed F. psychrophilum/FCA. Following immunization and bacterial challenge of rainbow trout fry, protective immunity was conferred in F. psychrophilum/FCA and saline/FCA groups with relative per cent survival values of up to 83 and 51, respectively. Significant protection was not observed in treatment groups immunized by immersion or i.p. without adjuvant at the challenge doses tested. Results suggest that stimulation of non-specific immune factors enhances the ability of fish to mount a protective immune response, but specific antibody appears necessary to provide near complete protection. In this study, an ELISA was developed to monitor anti- F. psychrophilum antibody production in trout. The relationship of such responses to protective immunity suggests that future vaccination strategies against coldwater disease may require stimulation of both the innate and adaptive arms of the immune response. [source] Protection against influenza virus infection by intranasal vaccine with surf clam microparticles (SMP) as an adjuvantJOURNAL OF MEDICAL VIROLOGY, Issue 7 2006Takeshi Ichinohe Abstract A safe and effective adjuvant is necessary to enhance mucosal immune responses for the development of an inactivated intranasal influenza vaccine. The present study demonstrated the effectiveness of surf clam microparticles (SMP) derived from natural surf clams as an adjuvant for an intranasal influenza vaccine. The adjuvant effect of SMP was examined when co-administered intranasally with inactivated A/PR8 (H1N1) influenza virus hemagglutinin vaccine in BALB/c mice. Administration of the vaccine with SMP induced a high anti-PR8 haemagglutinin (HA)-specific immunoglobulin A (IgA) response in the nasal wash and immunoglobulin G (IgG) response in the serum, resulting in protection against both nasal-restricted infection and lethal lung infection by A/PR8 virus. In addition, administration of SMP with A/Yamagata (H1N1), A/Beijing (H1N1), or A/Guizhou (H3N2) vaccine conferred complete protection against A/PR8 virus challenge in the nasal infection model, suggesting that SMP adjuvanted vaccine can confer cross-protection against variant influenza viruses. The use of SMP is suggested as a new safe and effective mucosal adjuvant for nasal vaccination against influenza virus infection. J. Med. Virol. 78:954,963, 2006. © 2006 Wiley-Liss, Inc. [source] Delayed pre-conditioning by 3-nitropropionic acid prevents 3,4-methylenedioxymetamphetamine-induced 5-HT deficitsJOURNAL OF NEUROCHEMISTRY, Issue 3 2010Elena Puerta J. Neurochem. (2010) 114, 843,852. Abstract The aim of the present study was to investigate whether late pre-conditioning using 3-nitropropionic acid (3NP) prevents the 5-hydroxytryptamine (5-HT) deficits caused by the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA) in the rat. For this purpose we administered 3NP 24 h before MDMA (3 × 5 mg/kg i.p., every 2 h) and rats were killed 7 days later. Pre-treatment of 3NP afforded complete protection against MDMA-induced 5-HT deficits independent of any effect on MDMA-induced hyperthermia or 5-HT transporter activity. To identify the transductional mechanisms responsible for the neuroprotective effect of 3NP, we first examined the involvement of nitric oxide (NO) by using selective inhibitors of all three nitric oxide synthase isoforms. Inhibition of endothelial and neuronal nitric oxide synthase, but not inducible nitric oxide synthase, reversed 3NP-induced pre-conditioning. The NO donor S -Nitroso- N -acetylpenicilamine mimicked 3NP effects further suggesting the involvement of NO in mediating 3NP protection. To investigate the involvement of NOS/soluble guanylate cyclase (sGC)/protein kinase G/mitochondrial ATP-sensitive potassium channels (mitoKATP) signaling pathway we examined the effect of 5-hydroxydecanoate (5-HD), a selective mitoKATP blocker, and 1H -(1,2,4)oxadiazolo[4,3- a]quinoxaline-1-one, a potent inhibitor of sGC, on 3NP-induced tolerance. 5-hydroxydecanoate, but not 1H -(1,2,4)oxadiazolo[4,3- a]quinoxaline-1-one, suppressed 3NP-mediated protection suggesting that mitoKATP opening, but not NO-mediated activation of sGC, participates in the mechanism underlying tolerance to MDMA. Our data also showed that the protective effect of 3NP was abolished by cycloheximide, supporting the involvement of de novo protein synthesis. In conclusion, 3NP-induced delayed tolerance against 5-HT deficits caused by MDMA occurs via NO production. [source] Activated JNK brings about accelerated apoptosis of Bcl-2-overexpressing C6 glioma cells on treatment with tamoxifenJOURNAL OF NEUROCHEMISTRY, Issue 1 2005Madhavi S. Moodbidri Abstract Tamoxifen causes apoptosis of malignant glial cells at a concentration that does not kill normal astrocytes. C6 glioma cells were stably transfected with a vector expressing Bcl-2 under the control of metallothionin promoter. Low leaky Bcl-2 expression offered complete protection against tamoxifen-induced apoptosis. High Bcl-2 levels, on the other hand, accelerated the apoptosis, with Bcl-2-overexpressing clones dying within 48 h of tamoxifen treatment as compared to 6 days for parental C6 cells. Overexpressed Bcl-2 is localized primarily in mitochondria and to a much lower extent in endoplasmic reticulum (ER). Only a minor fraction of the overexpressed Bcl-2 gets phosphorylated in tamoxifen-treated cells and the phosphorylation does not affect its binding to Bax. Tamoxifen treatment of Bcl-2-overexpressing clones was found to result in activation of c-Jun N-terminal kinase (JNK) and p38 kinase. Inhibition of JNK but not p38 kinase completely abrogated the accelerated apoptosis. Constitutively expressed endogenous c-Jun was found to be phosphorylated, resulting in increased activator protein 1 (AP-1) DNA-binding activity. Expression of Fas ligand (FasL), an AP-1 transcriptional target, increased during accelerated cell death. This presumably brought about activation of caspase 8, as inhibition of caspase 8 blocked the apoptosis. The JNK/c-Jun/AP-1/FasL pathway could be considered as a potential target for the therapy of gliomas. [source] Iron accelerates the conversion of dopamine-oxidized intermediates into melanin and provides protection in SH-SY5Y cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 1 2005Yasuhiko Izumi Abstract Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons in the substantia nigra (SN), and it has been suggested that dopamine is one of the main endogenous toxins in the genesis of PD. We demonstrated that thiol antioxidants (the reduced form of glutathione, N -acetyl-L-cysteine, and L-cysteine), which conjugate with one dopamine oxidation intermediate, o -quinone, provided almost complete protection from dopamine-mediated toxicity in SH-SY5Y, a human neuroblastoma cell line. In contrast, catalase partially provided protection against cell death caused by dopamine. These data suggest that the generation of dopamine oxidation intermediates, rather than hydrogen peroxide, plays a pivotal role in dopamine-induced toxicity. Iron accumulated in the SN of patients with PD can cause dopaminergic neuronal degeneration by enhancing oxidative stress. However, we found that iron reduced the total amounts of dopamine oxidation intermediates and enhanced the formation of melanin, a final product of dopamine oxidation. Also, addition of iron inhibited dopamine-induced cytotoxicity. These results suggest that iron can provide protection when it accelerates the conversion of dopamine oxidation intermediates. © 2005 Wiley-Liss, Inc. [source] Anthrax vaccine powder formulations for nasal mucosal deliveryJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 1 2006Ge Jiang Abstract Anthrax remains a serious threat worldwide as a bioterror agent. A second-generation anthrax vaccine currently under clinical evaluation consists of a recombinant Protective Antigen (rPA) of Bacillus anthracis. We have previously demonstrated that complete protection against inhalational anthrax can be achieved in a rabbit model, by intranasal delivery of a powder rPA formulation. Here we describe the preformulation and formulation development of such powder formulations. The physical stability of rPA was studied in solution as a function of pH and temperature using circular dichroism (CD), and UV-visible absorption and fluorescence spectroscopies. Extensive aggregation of rPA was observed at physiological temperatures. An empirical phase diagram, constructed using a combination of CD and fluorescence data, suggests that rPA is most thermally stable within the pH range of 6,8. To identify potential stabilizers, a library of GRAS excipients was screened using an aggregation sensitive turbidity assay, CD, and fluorescence. Based on these stability profiles, spray freeze-dried (SFD) formulations were prepared at pH 7,8 using trehalose as stabilizer and a CpG-containing oligonucleotide adjuvant. SFD formulations displayed substantial improvement in storage stability over liquid formulations. In combination with noninvasive intranasal delivery, such powder formulations may offer an attractive approach for mass biodefense immunization. © 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:80,96, 2006 [source] Review article: the therapeutic and prognostic benefit of portal pressure reduction in cirrhosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2008C. K. TRIANTOS Summary Background, Hepatic venous pressure gradient (HVPG) measurement is not a routinely used technique, despite its therapeutic and prognostic value. Aim, To review the role of HVPG from published literature. Methods, Systematic literature review. Results, In acute variceal bleeding, HVPG is prognostic identifying ,difficult to treat' group, which now has defined clinical correlations. In secondary prevention of portal hypertensive bleeding, a reduction to ,12 mmHg confers near complete protection against rebleeding. The target of ,20% HVPG reduction from baseline needs prospective assessment to test a change of therapy, if no reduction occurs. The acute HVPG response to beta-blockade needs further assessment. In primary prevention, the cost-effectiveness of HVPG measurement is not favourable given the efficacy of medical therapy. In chronic liver disease, wedge hepatic venous pressure (WHVP) is prognostic for survival. Pharmacological reduction in portal pressure decreases complications and improves survival, possibly independent of a concomitant improvement in liver function. This latter requires urgent confirmation as it is clinically very relevant. HVPG monitoring can be used to assess anti-viral therapy particularly in cirrhosis, ergonomically combined with transjugular biopsy. Conclusions, The prognostic and therapeutic value of HVPG is established beyond portal hypertensive bleeding for which there are some clinical surrogates. HVPG measurement should now be part of everyday clinical practice. [source] Repellency and toxicity of aromatic plant extracts against the mosquito Culex pipiens molestus (Diptera: Culicidae)PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 6 2005Abdallah F Traboulsi Abstract The insecticidal activities of essential oil extracts from leaves, flowers and roots of aromatic plants against fourth-instar larvae of the mosquito Culex pipiens molestus Forskål were determined. Extracts of Foeniculum vulgare Mill were the most toxic, followed by those of Ferula hermonis Boiss, Citrus sinensis Osbeck, Pinus pinea L, Laurus nobilis L and Eucalyptus spp with LC50 values of 24.5, 44.0, 60.0, 75.0, 117.0 and 120.0 mg litre,1, respectively. Combination tests between the LC50 and the maximum sub-lethal concentration (MSLC) were determined. Over 20 major components were identified in extracts from each plant species tested. Five essential oils and nine pure components were studied for their repellency against mosquito bites. Terpineol and 1,8-cineole were the most effective against Culex pipiens molestus bites offering complete protection for 1.6 and 2 h, respectively. Copyright © 2005 Society of Chemical Industry [source] A combined structural dynamics approach identifies a putative switch in factor VIIa employed by tissue factor to initiate blood coagulationPROTEIN SCIENCE, Issue 4 2007Ole H. Olsen Abstract Coagulation factor VIIa (FVIIa) requires tissue factor (TF) to attain full catalytic competency and to initiate blood coagulation. In this study, the mechanism by which TF allosterically activates FVIIa is investigated by a structural dynamics approach that combines molecular dynamics (MD) simulations and hydrogen/deuterium exchange (HX) mass spectrometry on free and TF-bound FVIIa. The differences in conformational dynamics from MD simulations are shown to be confined to regions of FVIIa observed to undergo structural stabilization as judged by HX experiments, especially implicating activation loop 3 (residues 365,374{216,225}) of the so-called activation domain and the 170-loop (residues 313,322{170A,175}) succeeding the TF-binding helix. The latter finding is corroborated by experiments demonstrating rapid deglycosylation of Asn322 in free FVIIa by PNGase F but almost complete protection in the presence of TF or an active-site inhibitor. Based on MD simulations, a key switch of the TF-induced structural changes is identified as the interacting pair Leu305{163} and Phe374{225} in FVIIa, whose mutual conformations are guided by the presence of TF and observed to be closely linked to the structural stability of activation loop 3. Altogether, our findings strongly support an allosteric activation mechanism initiated by the stabilization of the Leu305{163}/Phe374{225} pair, which, in turn, stabilizes activation loop 3 and the S1 and S3 substrate pockets, the activation pocket, and N-terminal insertion. [source] Biodiversity of semi-arid Mediterranean grasslands: Impact of grazing and afforestationAPPLIED VEGETATION SCIENCE, Issue 2 2007M.A. Alrababah Zohary & Feinbrun (1966,1986) Abstract Question: What is the impact of grazing and/or afforestation on grassland diversity, species composition and cover parameters? Location: Semi-arid Mediterranean grasslands of Jordan. Methods: Vegetation, litter, bare soil and rock cover were compared among four management types , free grazing and protected from grazing with three levels of tree cover. Species composition, plant cover, species richness and evenness were used to evaluate differences in vegetation among management types. Species composition differences among management types were also investigated. Results: Semi-arid Mediterranean grasslands harbour appreciable levels of plant biodiversity. Grazing did not affect plant diversity, indicating the high resilience against and adaptation to grazing; however,grazing affected species composition and cover parameters. Afforestation seems to protect soil through higher litter cover but its impact on plant biodiversity was negative and markedly affected species composition. Conclusions: Neither protection from grazing or massive afforestation alone are sufficient for conserving biodiversity in this system. A management model is suggested where the landscape should be maintained as a mosaic of four management types: complete protection from grazing, grazing rotation, planting sparse trees in eroded areas and revegetating degraded areas using native, herbaceous and grazing tolerant species. [source] Effect of nitric oxide on iron-mediated cytotoxicity in primary cultured renal proximal tubulesCELL BIOCHEMISTRY AND FUNCTION, Issue 4 2001Zhao-long Wu Abstract Nitric oxide (NO) has been proved to be a mediator of hypoxic injury in renal proximal tubules (PT), but its effect on iron-induced cytotoxicity has remained little known. In this study, we observed the relationship between NO production and lactate dehydrogenase (LDH) release in primary proximal tubular epithelia co-incubated with different doses of NTA-Fe and lipopolysaccharide (LPS) alone or in combination. NO production was monitored by NO2 concentration in supernatants based on the Griess reaction; while the semi-quantitative RT-PCR was applied to detect the inducible nitric oxide synthase (iNOS) mRNA level induced by NTA-Fe and LPS together. In addition, experimental groups were subjected to reactive oxygen species (ROS) scavengers to determine the impact of the interaction between NO and ROS on iron-mediated cytotoxicity. After a 12-h co-incubation, we found that NTA-Fe increased both LDH release and 2, production in a dose-dependent manner (P,<,0.001). The level of iNOS mRNA induced by LPS was enhanced by 500 ,m NTA-Fe (P,<,0.01), lower or higher concentrations had no effect. However, the supernatant 2, level in the same group did not change significantly (P,>,0.05) although tubular injury was aggravated (P,<,0.001). The addition of l -arginine increased LDH release from 25.05,±,8.36% in the iron group to 38.67,±,7.67% in iron plus LPS group (P,<,0.05); concomitantly, l -NAME mitigated iron toxicity in LPS-treated PT (P,<,0.05). Hydroxyl scavengers provided complete protection against iron-mediated cytotoxicity (P,<,0.001), but the decrease of 2, production was only significant in the LPS-treated group. In contrast, SOD was partially effective in the LPS group (P,<,0.05) whereas the 2, level in the supernatant was inversely raised (P,<,0.05). GSH had no effect on either iron toxicity or 2, production. Thus, we conclude that NO can exacerbate the cytotoxicity caused by NTA-Fe in cultured proximal tubular epithelia, but NO is not the only factor. NTA-Fe could enhance the upregulation of iNOS transcription induced by LPS in a specific concentration range, and its regulation of NO production might also involve a post-transcription mechanism. The hydroxyl group is the major mediator in our model and the pro-oxidant role of NO is probably due to its ability to promote the Fenton reaction and form both ONOO, and ,OH via its interaction with ROS. Copyright © 2001 John Wiley & Sons, Ltd. [source] Effective Insect Repellent Formulation in both Surfactantless and Classical Microemulsions with a Long-Lasting Protection for Human BeingsCHEMISTRY & BIODIVERSITY, Issue 6 2009Jeremy Drapeau Abstract The aim of this work is to develop a new generation of repellent products with a long-lasting protection based on a natural component, para -menthane-3,8-diol (PMD). The active is first rendered soluble in a surfactantless microemulsion (H2O/iPrOH/PMD) and then in classical microemulsions. The presence of self-associated nanostructures is detected by dynamic light scattering (DLS). A synergetic system of surfactants (Cremophor®RH40 and Texapon®N70) is used. Additionally, 2-ethylhexane-1,3-diol and ethyl (,)-(S)-lactate are incorporated. The final product contains, as main components, 46% of H2O, 25% of iPrOH, 20% of non-H2O-soluble PMD, and only 4% of surfactants. Investigations of lasting protection on human volunteers are carried out using a cage test bioassay protocol and Aedes aegypti mosquitoes. A complete protection of 315,min is found on the test persons using the surfactantless microemulsion. An extension is observed with the final formulation to reach a mean of complete protection of 385,min. This study demonstrates that alternative formulations using a natural active instead of synthetic chemicals like N,N -diethyl- m -methylbenzamide (DEET) can be efficient for human protection against mosquitoes. [source] | |||||||||||||||||||