Home About us Contact
|
Home About us Contact | ||
|
|
||
Increased Response (increased + response)
Selected AbstractsPlasma facilitated delivery of DNA to skinBIOTECHNOLOGY & BIOENGINEERING, Issue 5 2009Richard J. Connolly Abstract Non-viral delivery of cell-impermeant drugs and DNA in vivo has traditionally relied upon either chemical or physical stress applied directly to target tissues. Physical methods typically use contact between an applicator, or electrode, and the target tissue and may involve patient discomfort. To overcome contact-dependent limitations of such delivery methodologies, an atmospheric helium plasma source was developed to deposit plasma products onto localized treatment sites. Experiments performed in murine skin showed that samples injected with plasmid DNA encoding luciferase and treated with plasma demonstrated increased levels of expression relative to skin samples that received injections of DNA alone. Increased response relative to injection alone was observed when either positive or negative voltage was used to generate the helium plasma. Quantitative results over a 26-day follow-up period showed that luciferase levels as high as 19-fold greater than the levels obtained by DNA injection alone could be achieved. These findings indicate that plasmas may compete with other physical delivery methodologies when skin is the target tissue. Biotechnol. Bioeng. 2009; 104: 1034,1040. © 2009 Wiley Periodicals, Inc. [source] Frontolimbic responses to emotional face memory: The neural correlates of first impressionsHUMAN BRAIN MAPPING, Issue 11 2009Theodore D. Satterthwaite Abstract First impressions, especially of emotional faces, may critically impact later evaluation of social interactions. Activity in limbic regions, including the amygdala and ventral striatum, has previously been shown to correlate with identification of emotional content in faces; however, little work has been done describing how these signals may influence emotional face memory. We report an event-related functional magnetic resonance imaging study in 21 healthy adults where subjects attempted to recognize a neutral face that was previously viewed with a threatening (angry or fearful) or nonthreatening (happy or sad) affect. In a hypothesis-driven region of interest analysis, we found that neutral faces previously presented with a threatening affect recruited the left amygdala. In contrast, faces previously presented with a nonthreatening affect activated the left ventral striatum. A whole-brain analysis revealed increased response in the right orbitofrontal cortex to faces previously seen with threatening affect. These effects of prior emotion were independent of task performance, with differences being seen in the amygdala and ventral striatum even if only incorrect trials were considered. The results indicate that a network of frontolimbic regions may provide emotional bias signals during facial recognition. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancerINTERNATIONAL JOURNAL OF CANCER, Issue 5 2006Gernot Hudelist Abstract Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin®) has become a valuable therapeutic option for patients with Her-2/neu -overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu -overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy. © 2005 Wiley-Liss, Inc. [source] Gene structure of an antimicrobial peptide from mandarin fish, Siniperca chuatsi (Basilewsky), suggests that moronecidins and pleurocidins belong in one family: the piscidinsJOURNAL OF FISH DISEASES, Issue 6 2007B J Sun Abstract The gene of piscidin, an antimicrobial peptide, has been cloned from the mandarin fish, Siniperca chuatsi. From the first transcription initiation site, the mandarin fish piscidin gene extends 1693 nucleotides to the end of the 3, untranslated region and contains four exons and three introns. A predicted 79-residue prepropeptide consists of three domains: a signal peptide (22 aa), a mature peptide (22 aa) and a C-terminal prodomain (35 aa). The shortage of XQQ motif in the prodomain of mandarin fish piscidin and the similar gene structure between moronecidins (piscidins) and pleurocidins may indicate that they are derived from the same ancestor gene. We thus suggest that piscidin should be used as a terminology for these antimicrobial peptides in the future. The mandarin fish piscidin mRNA was abundant in intestine, spleen, pronephros and kidney analysed by real-time polymerase chain reaction. After stimulation with lipopoly saccharides (LPS), a marked increase in transcripts was observed in most tissues, indicating that piscidin is not only a constitutively expressed molecule, but also has an increased response to bacterial infection. The synthetic, amidated mandarin fish piscidin exhibited different antimicrobial activity against different fish bacterial pathogens, especially against species of Aeromonas, which may to certain extent reflect the pathogenicity of these bacteria. [source] Autonomous contractile activity in the isolated rat bladder is modulated by a TRPV1 dependent mechanism,NEUROUROLOGY AND URODYNAMICS, Issue 3 2007Thomas Gevaert Abstract Aims Resiniferatoxin (RTX), a vanilloid compound and agonist of the transient receptor potential channel 1 (TRPV1), is known for its beneficial effects on neurogenic detrusor overactivity. The mainstream rationale for its use is the desensitization of TRPV1 on sensory bladder afferents. However, recent findings showed that TRPV1 is present in other cell types in the bladder. To eliminate the effects of RTX on spinal and central neural circuits, we investigated autonomous contractility in normal and neurogenic rat bladders after treatment with RTX. Methods Female Wistar rats were made paraplegic at vertebral level T8,T9. Animals were intravesically pre-treated with vehicle (ethanol 5%) or RTX (100 nM) and sacrificed after 72 hr. Each bladder was excised and placed in a heated organ bath, where intravesical pressures were measured. Effects on contractile parameters of intravesical volume load, the non-selective muscarinic receptor agonist carbachol (CA) and electrical stimulation (ES) of nerves were studied in both groups. Results In RTX-treated normal bladders we found shorter contractions with higher amplitude than in control bladders (P,<,0.05). In RTX-treated neurogenic bladders the amplitude and duration of autonomous contractions were increased compared with controls (P,<,0.05). Furthermore RTX induced an increased response to CA and to ES (P,<,0.05). Conclusions RTX significantly affected the properties of autonomous bladder contractile activity. This provides evidence for local effects of RTX on bladder contractile activity, which are not mediated by afferent neural pathways and which may contribute to the beneficial effects on detrusor overactivity. TRPV1 and TRPV1+ cells seem to play an important role in (autonomous) bladder contractility. Neurourol. Urodynam. 26:424,432, 2007. © 2006 Wiley-Liss, Inc. [source] Rice root colonisation by mycorrhizal and endophytic fungi in aerobic soilANNALS OF APPLIED BIOLOGY, Issue 2 2009M. Vallino Abstract Arbuscular mycorrhizal (AM) fungi are ubiquitous root symbionts that form intimate associations with the majority of plants growing in aerobic soil; fungal endophytes live internally, either intercellularly or intracellularly, and asymptomatically within plant tissues. Their presence is correlated with an increased response to biotic and abiotic stress. The populations of AM and of endophytic fungi were studied in the roots of different rice varieties grown in aerobic condition, in experimental fields in Vercelli, North Italy. All the rice varieties resulted colonised by AM fungi with a percentage of arbuscularisation ranging between 4% and 28%. Preliminary molecular analyses on some rice varieties showed that the AM population was composed of fungi identified as Glomus intraradices, on the basis of 18S ribosomal gene. All the varieties analysed but one resulted in colonisation by endophytic fungi. About 300 fungal isolates were obtained, belonging mainly to the genera Neotyphodium, Stagonospora and Penicillium. [source] AI-2 biosynthesis module in a magnetic nanofactory alters bacterial response via localized synthesis and deliveryBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2009Rohan Fernandes Abstract Nanofactories are nano-dimensioned and comprised of modules serving various functions that alter the response of targeted cells when deployed by locally synthesizing and delivering cargo to the surfaces of the targeted cells. In its basic form, a nanofactory consists of a minimum of two functional modules: a cell capture module and a synthesis module. In this work, magnetic nanofactories that alter the response of targeted bacteria by the localized synthesis and delivery of the "universal" bacterial quorum sensing signal molecule autoinducer AI-2 are demonstrated. The magnetic nanofactories consist of a cell capture module (chitosan-mag nanoparticles) and an AI-2 biosynthesis module that contains both AI-2 biosynthetic enzymes Pfs and LuxS on a fusion protein (His-LuxS-Pfs-Tyr, HLPT) assembled together. HLPT is hypothesized to be more efficient than its constituent enzymes (used separately) at conversion of the substrate SAH to product AI-2 on account of the proximity of the two enzymes within the fusion protein. HLPT is demonstrated to be more active than the constituent enzymes, Pfs and LuxS, over a wide range of experimental conditions. The magnetic nanofactories (containing bound HLPT) are also demonstrated to be more active than free, unbound HLPT. They are also shown to elicit an increased response in targeted Escherichia coli cells, due to the localized synthesis and delivery of AI-2, when compared to the response produced by the addition of AI-2 directly to the cells. Studies investigating the universality of AI-2 and unraveling AI-2 based quorum sensing in bacteria using magnetic nanofactories are envisioned. The prospects of using such multi-modular nanofactories in developing the next generation of antimicrobials based on intercepting and interrupting quorum sensing based signaling are discussed. Biotechnol. Bioeng. 2009;102: 390,399. © 2008 Wiley Periodicals, Inc. [source] Noradrenergic depletion increases inflammatory responses in brain: effects on I,B and HSP70 expressionJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Michael T. Heneka Abstract The inflammatory responses in many cell types are reduced by noradrenaline (NA) binding to ,-adrenergic receptors. We previously demonstrated that cortical inflammatory responses to aggregated amyloid beta (A,) are increased if NA levels were first depleted by lesioning locus ceruleus (LC) noradrenergic neurons, which replicates the loss of LC occurring in Alzheimer's disease. To examine the molecular basis for increased responses, we used the selective neurotoxin DSP4 to lesion the LC, and then examined levels of putative anti-inflammatory molecules. Inflammatory responses were achieved by injection of aggregated A,1,42 peptide and IL-1, into frontal cortex, which induced neuronal inducible nitric oxide synthase (iNOS) and microglial IL-1, expression. DSP4-treatment reduced basal levels of nuclear factor kappa B (NF-,B) inhibitory I,B proteins, and of heat shock protein (HSP)70. Inflammatory responses were prevented by co-injection (ibuprofen or ciglitzaone) or oral administration (pioglitazone) of peroxisome proliferator-activated receptor gamma (PPAR,) agonists. Treatment with PPAR, agonists restored I,B,, I,B,, and HSP70 levels to values equal or above those observed in control animals, and reduced activation of cortical NF-,B. These results suggest that noradrenergic depletion reduces levels of anti-inflammatory molecules which normally limit cortical responses to A,, and that PPAR, agonists can reverse that effect. These findings suggest one mechanism by which PPAR, agonists could provide benefit in neurological diseases having an inflammatory component. [source] Atomised lidocaine for airway topical anaesthesia in the morbidly obese: 1% compared with 2%,ANAESTHESIA, Issue 1 2010C. Woodruff Summary Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in morbidly obese patients was evaluated using two doses of local anaesthetic. In this randomised, blinded prospective study, 40 ml of atomised 1% (n = 11) or 2% (n = 10) lidocaine was administered with high oxygen flow as carrier. Outcomes included time for intubation, patient tolerance to airway manipulation, haemodynamic parameters, the bronchoscopist's overall satisfaction, and serial serum lidocaine concentrations. Patients receiving lidocaine 1% had a longer mean (SD) time from the start of topicalisation to tracheal tube cuff inflation than those receiving lidocaine 2% (8.6 (0.9) min vs 6.9 (0.5) min, respectively; p < 0.05). Patients in the 1% cohort demonstrated increased responses to airway manipulation (p < 0.0001), reflecting lower bronchoscopist's satisfaction scores (p < 0.03). Haemodynamic responses to topicalisation and airway manipulation were similar in both groups. Peak plasma concentration was lower in the 1% group (mean (SD) 1.4 (0.3) and 3.8 (0.5) ,g.ml,1, respectively; p < 0.001). Airway anaesthesia using atomised lidocaine for awake oral fibreoptic intubation in the morbidly obese is efficacious, rapid and safe. Compared with lidocaine 1%, the 2% dose provides superior intubating conditions. [source] Neuropeptide Y modulates effects of bradykinin and prostaglandin E2 on trigeminal nociceptors via activation of the Y1 and Y2 receptorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2007J L Gibbs Background and Purpose: Although previous studies have demonstrated that neuropeptide Y (NPY) modulates nociceptors, the relative contributions of the Y1 and Y2 receptors are unknown. Therefore, we evaluated the effect of Y1 and Y2 receptor activation on nociceptors stimulated by bradykinin (BK) and prostaglandin E2 (PGE2). Experimental approach: Combined immunohistochemistry (IHC) with in situ hybridization (ISH) demonstrated that Y1 - and Y2 -receptors are collocated with bradykinin 2 (B2)-receptors in rat trigeminal ganglia (TG). The relative functions of the Y1 and Y2 receptors in modulating BK/PGE2 -evoked CGRP release and increased intracellular calcium levels in cultured TG neurons were evaluated. Key results: The Y1 and Y2 receptors are co-expressed with B2 in TG neurons, suggesting the potential for direct NPY modulation of BK responses. Pretreatment with the Y1 agonist [Leu31,Pro34]-NPY, inhibited BK/PGE2 -evoked CGRP release. Conversely, pretreatment with PYY(3-36), a Y2 agonist, increased BK/PGE2 evoked CGRP release. Treatment with NPY evoked an overall inhibitory effect, although of lesser magnitude. Similarly, [Leu31,Pro34]-NPY inhibited BK/PGE2 -evoked increases in intracellular calcium levels whereas PYY(3-36) increased responses. NPY inhibition of BK/PGE2 -evoked release of CGRP was reversed by the Y1 receptor antagonist, BIBO3304, and higher concentrations of BIBO3304 significantly facilitated CGRP release. The Y2 receptor antagonist, BIIE0246, enhanced the inhibitory NPY effects. Conclusions and implications: These results demonstrate that NPY modulation of peptidergic neurons is due to net activation of inhibitory Y1 and excitatory Y2 receptor systems. The relative expression or activity of these opposing receptor systems may mediate dynamic responses to injury and pain. British Journal of Pharmacology (2007) 150, 72,79. doi:10.1038/sj.bjp.0706967 [source] | |||||||||||||