Metabolic and stress-related roles of prolactin-releasing peptide.

Science.gov (United States)

Onaka, Tatsushi; Takayanagi, Yuki; Leng, Gareth

2010-05-01

In the modern world, improvements in human health can be offset by unhealthy lifestyle factors, including the deleterious consequences of stress and obesity. For energy homeostasis, humoral factors and neural afferents from the gastrointestinal tract, in combination with long-term nutritional signals, communicate information to the brain to regulate energy intake and expenditure. Energy homeostasis and stress interact with each other, and stress affects both food intake and energy expenditure. Prolactin-releasing peptide, synthesized in discrete neuronal populations in the hypothalamus and brainstem, plays an important role in integrating these responses. This review describes how prolactin-releasing peptide neurons receive information concerning both internal metabolic states and environmental conditions, and play a key role in energy homeostasis and stress responses. 2010 Elsevier Ltd. All rights reserved.

Different growth hormone (GH) response to GH-releasing peptide and GH-releasing hormone in hyperthyroidism.

Science.gov (United States)

Ramos-Dias, J C; Pimentel-Filho, F; Reis, A F; Lengyel, A M

1996-04-01

Altered GH responses to several pharmacological stimuli, including GHRH, have been found in hyperthyroidism. The mechanisms underlying these disturbances have not been fully elucidated. GH-releasing peptide-6 (GHRP-6) is a synthetic hexapeptide that specifically stimulates GH release both in vitro and in vivo. The mechanism of action of GHRP-6 is unknown, but it probably acts by inhibiting the effects of somatostatin on GH release. The aim of this study was to evaluate the effects of GHRP-6 on GH secretion in patients with hyperthyroidism (n = 9) and in control subjects (n = 9). Each subject received GHRP-6 (1 microg/kg, iv), GHRH (100 microg, iv), and GHRP-6 plus GHRH on 3 separate days. GH peak values (mean +/- SE; micrograms per L) were significantly lower in hyperthyroid patients compared to those in control subjects after GHRH alone (9.0 +/- 1.3 vs. 27.0 +/- 5.2) and GHRP-6 plus GHRH (22.5 +/- 3.5 vs. 83.7 +/- 15.2); a lack of the normal synergistic effect of the association of both peptides was observed in thyrotoxicosis. However, a similar GH response was seen in both groups after isolated GHRP-6 injection (31.9 +/- 5.7 vs. 23.2 +/- 3.9). In summary, we have shown that hyperthyroid patients have a normal GH response to GHRP-6 together with a blunted GH responsiveness to GHRH. Our data suggest that thyroid hormones modulate GH release induced by these two peptides in a differential way.

Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins.

Science.gov (United States)

Nongonierma, Alice B; FitzGerald, Richard J

2018-06-01

Milk proteins have been extensively studied for their ability to yield a range of bioactive peptides following enzymatic hydrolysis/digestion. However, many hurdles still exist regarding the widespread utilization of milk protein-derived bioactive peptides as health enhancing agents for humans. These mostly arise from the fact that most milk protein-derived bioactive peptides are not highly potent. In addition, they may be degraded during gastrointestinal digestion and/or have a low intestinal permeability. The targeted release of bioactive peptides during the enzymatic hydrolysis of milk proteins may allow the generation of particularly potent bioactive hydrolysates and peptides. Therefore, the development of milk protein hydrolysates capable of improving human health requires, in the first instance, optimized targeted release of specific bioactive peptides. The targeted hydrolysis of milk proteins has been aided by a range of in silico tools. These include peptide cutters and predictive modeling linking bioactivity to peptide structure [i.e., molecular docking, quantitative structure activity relationship (QSAR)], or hydrolysis parameters [design of experiments (DOE)]. Different targeted enzymatic release strategies employed during the generation of milk protein hydrolysates are reviewed herein and their limitations are outlined. In addition, specific examples are provided to demonstrate how in silico tools may help in the identification and discovery of potent milk protein-derived peptides. It is anticipated that the development of novel strategies employing a range of in silico tools may help in the generation of milk protein hydrolysates containing potent and bioavailable peptides, which in turn may be used to validate their health promoting effects in humans. Graphical abstract The targeted enzymatic hydrolysis of milk proteins may allow the generation of highly potent and bioavailable bioactive peptides.

Improvement of autism spectrum disorder symptoms in three children by using gastrin-releasing peptide.

Science.gov (United States)

Becker, Michele Michelin; Bosa, Cleonice; Oliveira-Freitas, Vera Lorentz; Goldim, José Roberto; Ohlweiler, Lygia; Roesler, Rafael; Schwartsmann, Gilberto; Riesgo, Rudimar Dos Santos

2016-01-01

To evaluate the safety, tolerability and potential therapeutic effects of gastrin-releasing peptide in three children with autistic spectrum disorder. Case series study with the intravenous administration of gastrin-releasing peptide in the dose of 160pmol/kg for four consecutive days. To evaluate the results, parental impressions the Childhood Autism Rating Scale (CARS) and the Clinical Global Impression (CGI) Scale. Each child underwent a new peptide cycle after two weeks. The children were followed for four weeks after the end of the infusions. The gastrin-releasing peptide was well tolerated and no child had adverse effects. Two children had improved social interaction, with a slight improvement in joint attention and the interaction initiatives. Two showed reduction of stereotypes and improvement in verbal language. One child lost his compulsion to bathe, an effect that lasted two weeks after each infusion cycle. Average reduction in CARS score was 2.8 points. CGI was "minimally better" in two children and "much better" in one. This study suggests that the gastrin-releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials-randomized, double-blinded, and with more children-are needed to better evaluate the possible therapeutic effects of gastrin-releasing peptide in autism. Copyright © 2016 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

Directory of Open Access Journals (Sweden)

Hiroaki Matsuo

2013-01-01

Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

NARCIS (Netherlands)

Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J.

2016-01-01

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis

Stress-induced release of GUT peptides in young women classified as restrained or unrestrained eaters.

Science.gov (United States)

Hilterscheid, Esther; Laessle, Reinhold

2015-12-01

Basal release of GUT peptides has been found to be altered in restrained eaters. Stress-induced secretion, however, has not yet been described, but could be a biological basis of overeating that exposes restrained eaters to a higher risk of becoming obese. The aim of the present study was to compare restrained and unrestrained eaters with respect to stress-induced release of the GUT peptides ghrelin and PYY. 46 young women were studied. Blood sampling for peptides was done before and after the Trier Social Stress Test. Ghrelin secretion after stress was significantly elevated in the restrained eaters, whereas no significant differences were detected for PYY. Stress-induced release of GUT peptides can be interpreted as a cause as well as a consequence of restrained eating.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

NARCIS (Netherlands)

Ripken, Dina; Wielen, van der Nikkie; Wortelboer, Heleen M.; Meijerink, Jocelijn; Witkamp, Renger F.; Hendriks, Henk F.J.

2016-01-01

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis

Improvement of autism spectrum disorder symptoms in three children by using gastrin‐releasing peptide

Directory of Open Access Journals (Sweden)

Michele Michelin Becker

2016-05-01

Conclusions: This study suggests that the gastrin‐releasing peptide is safe and may be effective in improving key symptoms of autism spectrum disorder, but its results should be interpreted with caution. Controlled clinical trials–randomized, double‐blinded, and with more children–are needed to better evaluate the possible therapeutic effects of gastrin‐releasing peptide in autism.

Carboxylic Terminated Thermo-Responsive Copolymer Hydrogel and Improvement in Peptide Release Profile

Directory of Open Access Journals (Sweden)

Zi-Kun Rao

2018-02-01

Full Text Available To improve the release profile of peptide drugs, thermos-responsive triblock copolymer poly (ε-caprolactone-co-p-dioxanone-b-poly (ethylene glycol-b-poly (ε-caprolactone-co-p-dioxanone (PECP was prepared and end capped by succinic anhydride to give its carboxylic terminated derivative. Both PCEP block copolymer and its end group modified derivative showed temperature-dependent reversible sol-gel transition in water. The carboxylic end group could significantly decrease the sol-gel transition temperature by nearly 10 °C and strengthen the gel due to enhanced intermolecular force among triblock copolymer chains. Furthermore, compared with the original PECP triblock copolymer, HOOC–PECP–COOH copolymer displayed a retarded and sustained release profile for leuprorelin acetate over one month while effectively avoiding the initial burst. The controlled release was believed to be related to the formation of conjugated copolymer-peptide pair by ionic interaction and enhanced solubility of drug molecules into the hydrophobic domains of the hydrogel. Therefore, carboxyl terminated HOOC–PECP–COOH hydrogel was a promising and well-exhibited sustained release carrier for peptide drugs with the advantage of being able to develop injectable formulation by simple mixing.

Uniformity of Peptide Release Is Maintained by Methylation of Release Factors

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William E. Pierson

2016-09-01

Full Text Available Termination of protein synthesis on the ribosome is catalyzed by release factors (RFs, which share a conserved glycine-glycine-glutamine (GGQ motif. The glutamine residue is methylated in vivo, but a mechanistic understanding of its contribution to hydrolysis is lacking. Here, we show that the modification, apart from increasing the overall rate of termination on all dipeptides, substantially increases the rate of peptide release on a subset of amino acids. In the presence of unmethylated RFs, we measure rates of hydrolysis that are exceptionally slow on proline and glycine residues and approximately two orders of magnitude faster in the presence of the methylated factors. Structures of 70S ribosomes bound to methylated RF1 and RF2 reveal that the glutamine side-chain methylation packs against 23S rRNA nucleotide 2451, stabilizing the GGQ motif and placing the side-chain amide of the glutamine toward tRNA. These data provide a framework for understanding how release factor modifications impact termination.

Extended Release of an Anti–Heparan Sulfate Peptide From a Contact Lens Suppresses Corneal Herpes Simplex Virus-1 Infection

Science.gov (United States)

Jaishankar, Dinesh; Buhrman, Jason S.; Valyi-Nagy, Tibor; Gemeinhart, Richard A.; Shukla, Deepak

2016-01-01

Purpose To prolong the release of a heparan sulfate binding peptide, G2-C, using a commercially available contact lens as a delivery vehicle and to demonstrate the ability of the released peptide to block herpes simplex virus-1 (HSV-1) infection using in vitro, ex vivo, and in vivo models of corneal HSV-1 infection. Methods Commercially available contact lenses were immersed in peptide solution for 5 days prior to determining the release of the peptide at various time points. Cytotoxicity of the released samples was determined by MTT and cell cycle analysis, and the functional activity of the released samples were assessed by viral entry, and viral spread assay using human corneal epithelial cells (HCE). The ability to suppress infection in human and pig cornea ex vivo and mouse in vivo models were also assessed. Results Peptide G2-C was released through the contact lens. Following release for 3 days, the peptide showed significant activity by inhibiting HSV-1 viral entry and spread in HCE cells. Significant suppression of infection was also observed in the ex vivo and in vivo experiments involving corneas. Conclusions Extended release of an anti–HS peptide through a commercially available contact lens can generate significant anti–HSV-1 activity and provides a new and effective way to control corneal herpes. PMID:26780322

Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals

Science.gov (United States)

Daberkow, DP; Brown, HD; Bunner, KD; Kraniotis, SA; Doellman, MA; Ragozzino, ME; Garris, PA; Roitman, MF

2013-01-01

Drugs of abuse hijack brain reward circuitry during the addiction process by augmenting action potential-dependent phasic dopamine release events associated with learning and goal-directed behavior. One prominent exception to this notion would appear to be amphetamine (AMPH) and related analogs, which are proposed instead to disrupt normal patterns of dopamine neurotransmission by depleting vesicular stores and promoting non-exocytotic dopamine efflux via reverse transport. This mechanism of AMPH action, though, is inconsistent with its therapeutic effects and addictive properties - which are thought to be reliant on phasic dopamine signaling. Here we used fast-scan cyclic voltammetry in freely moving rats to interrogate principal neurochemical responses to AMPH in the striatum and relate these changes to behavior. First, we showed that AMPH dose-dependently enhanced evoked dopamine responses to phasic-like current pulse trains for up to two hours. Modeling the data revealed that AMPH inhibited dopamine uptake but also unexpectedly potentiated vesicular dopamine release. Second, we found that AMPH increased the amplitude, duration and frequency of spontaneous dopamine transients, the naturally occurring, non-electrically evoked, phasic increases in extracellular dopamine. Finally, using an operant sucrose reward paradigm, we showed that low-dose AMPH augmented dopamine transients elicited by sucrose-predictive cues. However, operant behavior failed at high-dose AMPH, which was due to phasic dopamine hyperactivity and the decoupling of dopamine transients from the reward predictive cue. These findings identify up-regulation of exocytotic dopamine release as a key AMPH action in behaving animals and support a unified mechanism of abused drugs to activate phasic dopamine signaling. PMID:23303926

Ultrashort peptide nanogels release in situ generated silver manoparticles to combat emerging antimicrobial resistance strains

KAUST Repository

Seferji, Kholoud; Susapto, Hepi Hari; Arab, Wafaa Talat Abdullah; Sharip, Ainur; Sundaramurthi, Dhakshinamoorthy; Rauf, Sakandar; Hauser, Charlotte

2017-01-01

Nanogels made from self-assembling ultrashort peptides (3-6 amino acids in size) are promising biomaterials for various biomedical applications such as tissue engineering, drug delivery, regenerative medicine, microbiology and biosensing.We have developed silver-releasing peptide nanogels with promising wound care applications. The peptide nanogels allow a precise control of in situ syntesized silver nanoparticles (AgNPs), using soley short UV radiation and no other chemical reducing agent. We propose these silver-releasing nanogels as excellent biomaterial to combat emerging antimicrobial resistant strains.

Ultrashort peptide nanogels release in situ generated silver manoparticles to combat emerging antimicrobial resistance strains

KAUST Repository

Seferji, Kholoud

2017-01-08

Nanogels made from self-assembling ultrashort peptides (3-6 amino acids in size) are promising biomaterials for various biomedical applications such as tissue engineering, drug delivery, regenerative medicine, microbiology and biosensing.We have developed silver-releasing peptide nanogels with promising wound care applications. The peptide nanogels allow a precise control of in situ syntesized silver nanoparticles (AgNPs), using soley short UV radiation and no other chemical reducing agent. We propose these silver-releasing nanogels as excellent biomaterial to combat emerging antimicrobial resistant strains.

Prolactin-releasing peptide: a new tool for obesity treatment

Czech Academy of Sciences Publication Activity Database

Kuneš, Jaroslav; Pražienková, V.; Popelová, A.; Mikulášková, Barbora; Zemenová, J.; Maletínská, L.

2016-01-01

Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: ED - Physiology Impact factor: 4.706, year: 2016

Gastrin-releasing peptide stimulates glycoconjugate release from feline trachea

International Nuclear Information System (INIS)

Lundgren, J.D.; Baraniuk, J.N.; Ostrowski, N.L.; Kaliner, M.A.; Shelhamer, J.H.

1990-01-01

The effect of gastrin-releasing peptide (GRP) on respiratory glycoconjugate (RGC) secretion was investigated in a feline tracheal organ culture model. RGC secretion was stimulated by GRP in a dose-dependent fashion at concentrations from 10(-8) to 10(-5) M (range 15-38% increase above control) with a peak effect within 0.5-1 h of incubation. GRP-(14-27), the receptor binding portion of GRP, and the related molecule, bombesin, also stimulated RGC secretion by approximately 20% above control. Acetyl-GRP-(20-27) stimulated RGC release by 10%, whereas GRP-(1-16) was inactive. Autoradiographic studies with 125I-GRP revealed that specific binding was restricted to the submucosal glands and the surface epithelium. A specific radioimmunoassay showed the content of GRP in feline trachea after extraction with ethanol-acetic acid to be 156 +/- 91 fmol/g wet wt. Indirect immunohistochemistry indicated that ganglion cells located just outside the cartilage contained GRP-immunoreactive materials. GRP is a novel mucus secretagogue that may participate in regulating airway mucosal gland secretion

Prolactin-releasing peptide: a new tool for obesity treatment

Czech Academy of Sciences Publication Activity Database

Kuneš, Jaroslav; Pražienková, Veronika; Popelová, Andrea; Mikulášková, Barbora; Zemenová, Jana; Maletínská, Lenka

2016-01-01

Roč. 230, č. 2 (2016), R51-R58 ISSN 0022-0795 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * obesity * GPR10 * anorexigenic * mice Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 4.706, year: 2016

Peptide Drug Release Behavior from Biodegradable Temperature-Responsive Injectable Hydrogels Exhibiting Irreversible Gelation

Directory of Open Access Journals (Sweden)

Kazuyuki Takata

2017-10-01

Full Text Available We investigated the release behavior of glucagon-like peptide-1 (GLP-1 from a biodegradable injectable polymer (IP hydrogel. This hydrogel shows temperature-responsive irreversible gelation due to the covalent bond formation through a thiol-ene reaction. In vitro sustained release of GLP-1 from an irreversible IP formulation (F(P1/D+PA40 was observed compared with a reversible (physical gelation IP formulation (F(P1. Moreover, pharmaceutically active levels of GLP-1 were maintained in blood after subcutaneous injection of the irreversible IP formulation into rats. This system should be useful for the minimally invasive sustained drug release of peptide drugs and other water-soluble bioactive reagents.

In Vivo Imaging of the Stability and Sustained Cargo Release of an Injectable Amphipathic Peptide-Based Hydrogel.

Science.gov (United States)

Oyen, Edith; Martin, Charlotte; Caveliers, Vicky; Madder, Annemieke; Van Mele, Bruno; Hoogenboom, Richard; Hernot, Sophie; Ballet, Steven

2017-03-13

Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH 2 , which has previously shown promising in vivo properties in terms of releasing morphine. In this study, the release of a small molecule, a peptide, and a protein cargo as representatives of the three major drug classes is directly visualized by in vivo fluorescence and nuclear imaging. In addition, the in vivo stability of the peptide hydrogel system is investigated through the use of a radiolabeled hydrogelator sequence. Although it is shown that the hydrogel remains present for several days, the largest decrease in volume takes place within the first 12 h of subcutaneous injection, which is also the time frame wherein the cargos are released. Compared to the situation in which the cargos are injected in solution, a prolonged release profile is observed up to 12 h, showing the potential of our hydrogel system as a scaffold for controlled drug delivery. Importantly, this study elucidates the release mechanism of the peptide hydrogel system that seems to be based on erosion of the hydrogel providing a generally applicable controlled release platform for small molecule, peptide, and protein drugs.

Gastrin-releasing peptide is a transmitter mediating porcine gallbladder contraction

DEFF Research Database (Denmark)

Schjoldager, Birgit; Poulsen, S.S.; Schmidt, P.

1991-01-01

We studied the role of gastrin-releasing peptide (GRP) for porcine gallbladder motility. Immunohistochemistry visualized nerve fibers containing GRP-like immunoreactivity in muscularis. GRP concentration dependently stimulated contractions of muscularis strips (ED50, 2.9 nM). Neuromedin B was les......-like immunoreactivity. Thus two neural inputs were defined: a cholinergic rapid onset-rapid offset excitation and a delayed, slow onset-slow offset excitation caused by release and subsequent binding of GRP to GRP-preferring receptors....

Short-term effects of beta-amyloid25-35 peptide aggregates on transmitter release in neuromuscular synapses.

Science.gov (United States)

Garcia, Neus; Santafé, Manel M; Tomàs, Marta; Lanuza, Maria A; Tomàs, Josep

2008-03-01

The beta-amyloid (AB) peptide25-35 contains the functional domain of the AB precursor protein that is both required for neurotrophic effects in normal neural tissues and is involved in the neurotoxic effects in Alzheimer disease. We demonstrated the presence of the amyloid precursor protein/AB peptide in intramuscular axons, presynaptic motor nerve terminals, terminal and myelinating Schwann cells, and the postsynaptic and subsarcolemmal region in the Levator auris longus muscle of adult rats by immunocytochemistry. Using intracellular recording, we investigated possible short-term functional effects of the AB fragment (0.1-10 micromol/L) on acetylcholine release in adult and newborn motor end plates. We found no change in evoked, spontaneous transmitter release or resting membrane potential of the muscle cells. A previous block of the presynaptic muscarinic receptor subtypes and a previous block or stimulation of protein kinase C revealed no masked effect of the peptide on the regulation of transmitter release. The aggregated form of AB peptide25-35, however, interfered acutely with acetylcholine release (quantal content reduction) when synaptic activity was maintained by electric stimulation. The possible relevance of this inhibition of neurotransmission by AB peptide25-35 to the pathogenesis of Alzheimer remains to be determined.

Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jing, E-mail: zhangjing@zjut.edu.cn; Li, Mengfei [Zhejiang University of Technology, College of Materials Science and Engineering (China); Yuan, Zhefan [Zhejiang University, Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Department of Chemical and Biological Engineering (China); Wu, Dan; Chen, Jia-da; Feng, Jie, E-mail: fengjie@zjut.edu.cn [Zhejiang University of Technology, College of Materials Science and Engineering (China)

2016-10-15

A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K{sub 10}), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K{sub 10}, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.Graphical abstractA novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for selective drug delivery in cancerous cells. MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would

Peptide profiling of bovine kefir reveals 236 unique peptides released from caseins during its production by starter culture or kefir grains.

Science.gov (United States)

Ebner, Jennifer; Aşçı Arslan, Ayşe; Fedorova, Maria; Hoffmann, Ralf; Küçükçetin, Ahmet; Pischetsrieder, Monika

2015-03-18

Kefir has a long tradition in human nutrition due to its presupposed health promoting effects. To investigate the potential contribution of bioactive peptides to the physiological effects of kefir, comprehensive analysis of the peptide profile was performed by nano-ESI-LTQ-Orbitrap MS coupled to nano-ultrahigh-performance liquid chromatography. Thus, 257 peptides were identified, mainly released from β-casein, followed by αS1-, κ-, and αS2-casein. Most (236) peptides were uniquely detected in kefir, but not in raw milk indicating that the fermentation step does not only increase the proteolytic activity 1.7- to 2.4-fold compared to unfermented milk, but also alters the composition of the peptide fraction. The influence of the microflora was determined by analyzing kefir produced from traditional kefir grains or commercial starter culture. Kefir from starter culture featured 230 peptide sequences and showed a significantly, 1.4-fold higher proteolytic activity than kefir from kefir grains with 127 peptides. A match of 97 peptides in both varieties indicates the presence of a typical kefir peptide profile that is not influenced by the individual composition of the microflora. Sixteen of the newly identified peptides were previously described as bioactive, including angiotensin-converting enzyme (ACE)-inhibitory, antimicrobial, immunomodulating, opioid, mineral binding, antioxidant, and antithrombotic effects. The present study describes a comprehensive peptide profile of kefir comprising 257 sequences. The peptide list was used to identify 16 bioactive peptides with ACE-inhibitory, antioxidant, antithrombotic, mineral binding, antimicrobial, immunomodulating and opioid activity in kefir. Furthermore, it was shown that a majority of the kefir peptides were not endogenously present in the raw material milk, but were released from milk caseins by proteases of the microbiota and are therefore specific for the product. Consequently, the proteolytic activity and the

The growth hormone (GH) response to GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2), GH-releasing hormone, and thyrotropin-releasing hormone in acromegaly.

Science.gov (United States)

Alster, D K; Bowers, C Y; Jaffe, C A; Ho, P J; Barkan, A L

1993-09-01

In patients with acromegaly, GH-producing pituitary tumors release GH in response to specific stimuli such as GH-releasing hormone (GHRH) and are also responsive to a variety of nonspecific stimuli, such as TRH or GnRH, and may exhibit paradoxical responses to glucose and dopamine. In healthy humans, the synthetic peptide GH-releasing peptide (GHRP) (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) releases GH by a putative mechanism of action that is independent of GHRH. How these tumors respond to GHRP is not well characterized. We studied the GH responses to GHRH, GHRP, and TRH stimulation in 11 patients with active acromegaly. The peak GH responses to GHRP and GHRH were not correlated (r = 0.57; P = 0.066). In contrast, the peak GH responses to GHRP and TRH were highly correlated (r = 0.95; P < 0.001). In conclusion, in patients with acromegaly, the GH response to GHRP is qualitatively normal and does not appear to depend on GHRH.

Effects of a synthetic bioactive peptide on neurite growth and nerve growth factor release in chondroitin sulfate hydrogels

OpenAIRE

Conovaloff, Aaron W.; Beier, Brooke L.; Irazoqui, Pedro P.; Panitch, Alyssa

2011-01-01

Previous work has revealed robust dorsal root ganglia neurite growth in hydrogels of chondroitin sulfate. In the current work, it was determined whether addition of a synthetic bioactive peptide could augment neurite growth in these matrices via enhanced binding and sequestering of growth factors. Fluorescence recovery after photobleaching studies revealed that addition of peptide slowed nerve growth factor diffusivity in chondroitin sulfate gels, but not in control gels of hyaluronic acid. F...

A Novel Delivery System for the Controlled Release of Antimicrobial Peptides: Citropin 1.1 and Temporin A

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Urszula Piotrowska

2018-05-01

Full Text Available Antimicrobial peptides (AMPs are prospective therapeutic options for treating multiple-strain infections. However, clinical and commercial development of AMPs has some limitations due to their limited stability, low bioavailability, and potential hemotoxicity. The purpose of this study was to develop new polymeric carriers as highly controlled release devices for amphibian peptides citropin 1.1 (CIT and temporin A (TEMP. The release rate of the active pharmaceutical ingredients (APIs was strongly dependent on the API characteristics and the matrix microstructure. In the current work, we investigated the effect of the polymer microstructure on in vitro release kinetics of AMPs. Non-contact laser profilometry, scanning electron microscopy (SEM, and differential scanning calorimetry (DSC were used to determine the structural changes during matrix degradation. Moreover, geno- and cytotoxicity of the synthesized new carriers were evaluated. The in vitro release study of AMPs from the obtained non-toxic matrices shows that peptides were released with near-zero-order kinetics. The peptide “burst release” effect was not observed. New devices have reached the therapeutic concentration of AMPs within 24 h and maintained it for 28 days. Hence, our results suggest that these polymeric devices could be potentially used as therapeutic options for the treatment of local infections.

Further studies on the structural requirements for mast cell degranulating (MCD) peptide-mediated histamine release.

Science.gov (United States)

Buku, A; Price, J A

2001-12-01

Mast cell degranulating (MCD) peptide was modified in its two disulfide bridges and in the two arginine residues in order to measure the ability of these analogs to induce histamine release from mast cells in vitro. Analogs prepared were [Ala(3,15)]MCD, [Ala(5,19)]MCD, [Orn(16)]MCD, and [Orn(7,16)]MCD. Their histamine-releasing activity was determined spectrofluorometrically with peritoneal mast cells. The monocyclic analogs in which the cysteine residues were replaced pairwise with alanine residues showed three-to ten-fold diminished histamine-releasing activity respectively, compared with the parent MCD peptide. Substantial increases in activity were observed where arginine residues were replaced by ornithines. The ornithine-mono substituted analog showed an almost six-fold increase and the ornithine-doubly substituted analog three-fold increase in histamine-releasing activity compared with the parent MCD peptide. The structural changes associated with these activities were followed by circular dichroism (CD) spectroscopy. Changes in the shape and ellipticity of the CD spectra reflected a role for the disulfide bonds and the two arginine residues in the overall conformation and biological activity of the molecule.

Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

Science.gov (United States)

Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

2017-08-01

Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

Gastrin-releasing peptide receptor imaging in human breast carcinoma versus immunohistochemistry

NARCIS (Netherlands)

de Wiele, Christophe Van; Phonteyne, Philippe; Pauwels, Patrick; Goethals, Ingeborg; Van den Broecke, Rudi; Cocquyt, Veronique; Dierckx, Rudi Andre

This study reports on the uptake of (99m)Tc-RP527 by human breast carcinoma and its relationship to gastrin-releasing peptide receptor (GRIP-R) expression as measured by immunohistochemistry (IHC). Methods: Nine patients referred because of a clinical diagnosis suggestive of breast carcinoma and 5

Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

Science.gov (United States)

Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

2016-07-01

Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and in vitro anti-cancer evaluation of luteinizing hormone-releasing hormone-conjugated peptide.

Science.gov (United States)

Deng, Xin; Qiu, Qianqian; Ma, Ke; Huang, Wenlong; Qian, Hai

2015-11-01

Luteinizing hormone-releasing hormone (LHRH) is a decapeptide hormone released from the hypothalamus and shows high affinity binding to the LHRH receptors. It is reported that several cancer cells also express LHRH receptors such as breast, ovarian, prostatic, bladder and others. In this study, we linked B1, an anti-cancer peptide, to LHRH and its analogs to improve the activity against cancer cells with LHRH receptor. Biological evaluation revealed that TB1, the peptide contains triptorelin sequence, present favorable anti-cancer activity as well as plasma stability. Further investigations disclosed that TB1 trigger apoptosis by activating the mitochondria-cytochrome c-caspase apoptotic pathway, it also exhibited the anti-migratory effect on cancer cells.

Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum.

Science.gov (United States)

Trompette, Aurélien; Claustre, Jean; Caillon, Fabienne; Jourdan, Gérard; Chayvialle, Jean Alain; Plaisancié, Pascale

2003-11-01

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-casomorphin-7 (1.2 x 10(-4) mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, beta-endorphin (1.2 x 10(-8) to 1.2 x 10(-6) mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10(-6) mol/L), a mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.

The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

Science.gov (United States)

Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

2012-08-03

N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

Disturbed release of gastrointestinal peptides in anorexia nervosa and in obesity.

Science.gov (United States)

Baranowska, B; Radzikowska, M; Wasilewska-Dziubinska, E; Roguski, K; Borowiec, M

2000-04-01

It is commonly accepted that some neuropeptides play an important role in the control of appetite and hormonal secretion. Several gastrointestinal peptides may affect on central control of appetite via vagal and spinal nerves. The aim of this study was to evaluate the release of gastrointestinal peptides in anorexia nervosa and in obesity, because in these diseases the disturbances in the control of appetite and hormonal secretion were found. Material consisted of 30 women with anorexia nervosa aged 16-29 years (mean 22 years) and 23 women with obesity aged 19-33 years (mean 29 years) and 25 lean women of control group. In women with anorexia nervosa as compared with control group we observed a significant increase of plasma vasoactive intestinal peptide (VIP) levels (p anorexia nervosa. These findings suggests that dysfunction of brain-gut axis may be also an important factor in the abnormal control of appetite axcept of hypothalamic dysfunction.

Strategies for the Activation and Release of the Membranolytic Peptide Melittin from Liposomes Using Endosomal pH as a Trigger.

Science.gov (United States)

Oude Blenke, E; Sleszynska, M; Evers, M J W; Storm, G; Martin, N I; Mastrobattista, E

2017-02-15

Endosomolytic peptides are often coupled to drug delivery systems to enhance endosomal escape, which is crucial for the delivery of macromolecular drugs that are vulnerable to degradation in the endolysosomal pathway. Melittin is a 26 amino acid peptide derived from bee venom that has a very high membranolytic activity. However, such lytic peptides also impose a significant safety risk when applied in vivo as they often have similar activity against red blood cells and other nontarget cell membranes. Our aim is to control the membrane-disrupting capacity of these peptides in time and space by physically constraining them to a nanocarrier surface in such a way that they only become activated when delivered inside acidic endosomes. To this end, a variety of chemical approaches for the coupling of lytic peptides to liposomes via functionalized PEG-lipids were explored, including maleimide-thiol chemistry, click-chemistry, and aldehyde-hydrazide chemistry. The latter enables reversible conjugation via a hydrazone bond, allowing for release of the peptide under endosomal conditions. By carefully choosing the conjugation site and by using a pH activated analog of the melittin peptide, lytic activity toward a model membrane is completely inhibited at physiological pH. At endosomal pH the activity is restored by hydrolysis of the acid-labile hydrazone bond, releasing the peptide in its most active, free form. Furthermore, using an analogue containing a nonhydrolyzable bond as a control, it was shown that the activity observed can be completely attributed to release of the peptide, validating dynamic covalent conjugation as a suitable strategy to maintain safety during circulation.

Distinct roles of exogenous opioid agonists and endogenous opioid peptides in the peripheral control of neuropathy-triggered heat pain.

Science.gov (United States)

Labuz, Dominika; Celik, Melih Ö; Zimmer, Andreas; Machelska, Halina

2016-09-08

Neuropathic pain often results from peripheral nerve damage, which can involve immune response. Local leukocyte-derived opioid peptides or exogenous opioid agonists inhibit neuropathy-induced mechanical hypersensitivity in animal models. Since neuropathic pain can also be augmented by heat, in this study we investigated the role of opioids in the modulation of neuropathy-evoked heat hypersensitivity. We used a chronic constriction injury of the sciatic nerve in wild-type and opioid peptide-knockout mice, and tested opioid effects in heat and mechanical hypersensitivity using Hargreaves and von Frey tests, respectively. We found that although perineural exogenous opioid agonists, including peptidergic ligands, were effective, the endogenous opioid peptides β-endorphin, Met-enkephalin and dynorphin A did not alleviate heat hypersensitivity. Specifically, corticotropin-releasing factor, an agent triggering opioid peptide secretion from leukocytes, applied perineurally did not attenuate heat hypersensitivity in wild-type mice. Exogenous opioids, also shown to release opioid peptides via activation of leukocyte opioid receptors, were equally analgesic in wild-type and opioid peptide-knockout mice, indicating that endogenous opioids do not contribute to exogenous opioid analgesia in heat hypersensitivity. Furthermore, exogenously applied opioid peptides were ineffective as well. Conversely, opioid peptides relieved mechanical hypersensitivity. Thus, both opioid type and sensory modality may determine the outcome of neuropathic pain treatment.

Anhydrous polymer-based coating with sustainable controlled release functionality for facile, efficacious impregnation, and delivery of antimicrobial peptides.

Science.gov (United States)

Lim, Kaiyang; Saravanan, Rathi; Chong, Kelvin K L; Goh, Sharon H M; Chua, Ray R Y; Tambyah, Paul A; Chang, Matthew W; Kline, Kimberly A; Leong, Susanna S J

2018-04-17

Anhydrous polymers are actively explored as alternative materials to overcome limitations of conventional hydrogel-based antibacterial coating. However, the requirement for strong organic solvent in polymerization reactions often necessitates extra protection steps for encapsulation of target biomolecules, lowering encapsulation efficiency, and increasing process complexity. This study reports a novel coating strategy that allows direct solvation and encapsulation of antimicrobial peptides (HHC36) into anhydrous polycaprolactone (PCL) polymer-based dual layer coating. A thin 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) film is layered onto the peptide-impregnated PCL as a diffusion barrier, to modulate and enhance release kinetics. The impregnated peptides are eventually released in a controlled fashion. The use of 2,2,2-trifluoroethanol (TFE), as polymerization and solvation medium, induces the impregnated peptides to adopt highly stable turned conformation, conserving peptide integrity, and functionality during both encapsulation and subsequent release processes. The dual layer coating showed sustained antibacterial functionality, lasting for 14 days. In vivo assessment using an experimental mouse wounding model demonstrated good biocompatibility and significant antimicrobial efficacy of the coating under physiological conditions. The coating was translated onto silicone urinary catheters and showed promising antibacterial efficacy, even outperforming commercial silver-based Dover cather. This anhydrous polymer-based platform holds immense potential as an effective antibacterial coating to prevent clinical device-associated infections. The simplicity of the coating process enhances its industrial viability. © 2018 Wiley Periodicals, Inc.

Peptide chemistry toolbox - Transforming natural peptides into peptide therapeutics.

Science.gov (United States)

Erak, Miloš; Bellmann-Sickert, Kathrin; Els-Heindl, Sylvia; Beck-Sickinger, Annette G

2018-06-01

The development of solid phase peptide synthesis has released tremendous opportunities for using synthetic peptides in medicinal applications. In the last decades, peptide therapeutics became an emerging market in pharmaceutical industry. The need for synthetic strategies in order to improve peptidic properties, such as longer half-life, higher bioavailability, increased potency and efficiency is accordingly rising. In this mini-review, we present a toolbox of modifications in peptide chemistry for overcoming the main drawbacks during the transition from natural peptides to peptide therapeutics. Modifications at the level of the peptide backbone, amino acid side chains and higher orders of structures are described. Furthermore, we are discussing the future of peptide therapeutics development and their impact on the pharmaceutical market. Copyright © 2018 Elsevier Ltd. All rights reserved.

Functions of two distinct prolactin-releasing peptides evolved from a common ancestral gene

Directory of Open Access Journals (Sweden)

Tetsuya eTachibana

2014-11-01

Full Text Available Prolactin-releasing peptide (PrRP is one of the RF-amide peptides and was originally identified in the bovine hypothalamus as a stimulator of prolactin (PRL release. Independently, another RF-amide peptide was found in Japanese crucian carp and named Carassius RFa (C-RFa, which shows high homology to PrRP and stimulates PRL secretion in teleost fish. Therefore, C-RFa has been recognized as fish PrRP. However, recent work has revealed that PrRP and C-RFa in non-mammalian vertebrates are encoded by separate genes originated through duplication of an ancestral gene. Indeed, both PrRP and C-RFa are suggested to exist in teleost, amphibian, reptile, and avian species. Therefore, we propose that non-mammalian PrRP (C-RFa be renamed PrRP2. Despite a common evolutionary origin, PrRP2 appears to be a physiological regulator of PRL, whereas this is not a consistent role for PrRP itself. Further work revealed that the biological functions of PrRP and PrRP2 are not limited solely to PRL release, because they are also neuromodulators of several hypothalamus-pituitary axes and are involved in some brain circuits related to the regulation of food intake, stress, and cardiovascular functions. However, these actions appear to be different among vertebrates. For example, central injection of PrRP inhibits feeding behavior in rodents and teleosts while it stimulates it in chicks. Therefore, both PrRP and PrRP2 have acquired diverse actions through evolution. In this review, we integrate the burgeoning information of structures, expression profiles, and multiple biological actions of PrRP in higher vertebrates, as well as those of PrRP2 in non-mammals.

Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.

Science.gov (United States)

Ripken, Dina; van der Wielen, Nikkie; Wortelboer, Heleen M; Meijerink, Jocelijn; Witkamp, Renger F; Hendriks, Henk F J

2016-06-01

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Peptides reproducibly released by in vivo digestion of beef meat and trout flesh in pigs.

Science.gov (United States)

Bauchart, Caroline; Morzel, Martine; Chambon, Christophe; Mirand, Philippe Patureau; Reynès, Christelle; Buffière, Caroline; Rémond, Didier

2007-12-01

Characterisation and identification of peptides (800 to 5000 Da) generated by intestinal digestion of fish or meat were performed using MS analyses (matrix-assisted laser desorption ionisation time of flight and nano-liquid chromatography electrospray-ionisation ion trap MS/MS). Four pigs fitted with cannulas at the duodenum and jejunum received a meal exclusively made of cooked Pectoralis profundus beef meat or cooked trout fillets. A protein-free meal, made of free amino acids, starch and fat, was used to identify peptides of endogenous origin. Peptides reproducibly detected in digesta (i.e. from at least three pigs) were evidenced predominantly in the first 3 h after the meal. In the duodenum, most of the fish- and meat-derived peptides were characteristic of a peptic digestion. In the jejunum, the majority of peptides appeared to result from digestion by chymotrypsin and trypsin. Despite slight differences in gastric emptying kinetics and overall peptide production, possibly in relation to food structure and texture, six and four similar peptides were released after ingestion of fish or meat in the duodenum and jejunum. A total of twenty-six different peptides were identified in digesta. All were fragments of major structural (actin, myosin) or sarcoplasmic (creatine kinase, glyceraldehyde-3-phosphate dehydrogenase and myoglobin) muscle proteins. Peptides were short ( digestion, some of them can be reproducibly observed in intestinal digesta.

Identification and Relative Quantification of Bioactive Peptides Sequentially Released during Simulated Gastrointestinal Digestion of Commercial Kefir.

Science.gov (United States)

Liu, Yufang; Pischetsrieder, Monika

2017-03-08

Health-promoting effects of kefir may be partially caused by bioactive peptides. To evaluate their formation or degradation during gastrointestinal digestion, we monitored changes of the peptide profile in a model of (1) oral, (2) gastric, and (3) small intestinal digestion of kefir. Matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy analyses revealed clearly different profiles between digests 2/3 and kefir/digest 1. Subsequent ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry identified 92 peptides in total (25, 25, 43, and 30, partly overlapping in kefir and digests 1, 2, and 3, respectively), including 16 peptides with ascribed bioactivity. Relative quantification in scheduled multiple reaction monitoring mode showed that many bioactive peptides were released by simulated digestion. Most prominently, the concentration of angiotensin-converting enzyme inhibitor β-casein 203-209 increased approximately 10 000-fold after combined oral, gastric, and intestinal digestion. Thus, physiological digestive processes may promote bioactive peptide formation from proteins and oligopeptides in kefir. Furthermore, bioactive peptides present in certain compartments of the gastrointestinal tract may exert local physiological effects.

Sacubitril/valsartan: beyond natriuretic peptides.

Science.gov (United States)

Singh, Jagdeep S S; Burrell, Louise M; Cherif, Myriam; Squire, Iain B; Clark, Andrew L; Lang, Chim C

2017-10-01

Natriuretic peptides, especially B-type natriuretic peptide (BNP), have primarily been regarded as biomarkers in heart failure (HF). However, they are also possible therapeutic agents due to their potentially beneficial physiological effects. The angiotensin receptor-neprilysin inhibitor, sacubitril/valsartan, simultaneously augments the natriuretic peptide system (NPS) by inhibiting the enzyme neprilysin (NEP) and inhibits the renin-angiotensin-aldosterone system (RAAS) by blocking the angiotensin II receptor. It has been shown to improve mortality and hospitalisation outcomes in patients with HF due to left ventricular systolic dysfunction. The key advantage of sacubitril/valsartan has been perceived to be its ability to augment BNP, while its other effects have largely been overlooked. This review highlights the important effects of sacubitril/valsartan, beyond just the augmentation of BNP. First we discuss how NPS physiology differs between healthy individuals and those with HF by looking at mechanisms like the overwhelming effects of RAAS on the NPS, natriuretic peptide receptor desensitisation and absolute natriuretic deficiency. Second, this review explores other hormones that are augmented by sacubitril/valsartan such as bradykinin, substance P and adrenomedullin that may contribute to the efficacy of sacubitril/valsartan in HF. We also discuss concerns that sacubitril/valsartan may interfere with amyloid-β homeostasis with potential implications on Alzheimer's disease and macular degeneration. Finally, we explore the concept of 'autoinhibition' which is a recently described observation that humans have innate NEP inhibitory capability when natriuretic peptide levels rise above a threshold. There is speculation that autoinhibition may provide a surge of natriuretic and other vasoactive peptides to rapidly reverse decompensation. We contend that by pre-emptively inhibiting NEP, sacubitril/valsartan is inducing this surge earlier during decompensation

Exogenous glucagon-like peptide-2 (GLP-2) augments GLP-2 receptor mRNA and maintains proglucagon mRNA levels in resected rats

DEFF Research Database (Denmark)

Koopmann, Matthew C; Nelson, David W; Murali, Sangita G

2008-01-01

BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor express...... augments adaptive growth and digestive capacity of the residual small intestine in a rat model of mid-small bowel resection by increasing plasma GLP-2 concentrations and GLP-2 receptor expression without diminishing endogenous proglucagon expression.......BACKGROUND: Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent proglucagon-derived hormone that stimulates intestinal adaptive growth. Our aim was to determine whether exogenous GLP-2 increases resection-induced adaptation without diminishing endogenous proglucagon and GLP-2 receptor...

Psyllium fiber-enriched meal strongly attenuates postprandial gastrointestinal peptide release in healthy young adults

DEFF Research Database (Denmark)

Karhunen, Leila J.; Juvonen, Kristiina R.; Flander, Sanna M.

2010-01-01

Dietary fiber (DF) and protein are essential constituents of a healthy diet and are well known for their high satiety impact. However, little is known about their influence on postprandial gastrointestinal (GI) peptide release. Our aim in this single-blind, randomized, cross-over study was to inv...

Antibacterial and antiproliferative peptides in synbiotic yogurt-Release and stability during refrigerated storage.

Science.gov (United States)

Sah, B N P; Vasiljevic, T; McKechnie, S; Donkor, O N

2016-06-01

The search for alternative therapeutics is on the rise due to the extensive increase in bacterial resistance to various conventional antibiotics and side effects of conventional cancer therapies. Bioactive peptides released from natural sources such as dairy foods by lactic acid bacteria have received attention as a potential source of biotherapeutic peptides. However, liberation of peptides in yogurt depends on proteolytic activities of the cultures used. Thus, this research was conducted to establish generation of inhibitory peptides in yogurt against pathogenic bacteria and cancer cells during storage at 4°C for 28d. Water-soluble crude peptide extracts were prepared by high-speed centrifugation of plain and probiotic yogurts supplemented with or without pineapple peel powder (PPP). The inhibition zones against Escherichia coli and Staphylococcus aureus by PPP-fortified probiotic yogurt at 28d of storage were, respectively, 25.89 and 11.72mm in diameter, significantly higher than that of nonsupplemented control yogurts. Antiproliferative activity against HT29 colon cancer cells was also significantly higher in probiotic yogurt with PPP than in nonsupplemented probiotic yogurt. Overall, crude water-soluble peptide extracts of the probiotic yogurt with PPP possessed stronger inhibitory activities against bacteria and cancer cells than controls, and these activities were maintained during storage. However, activities were lowered substantially during in vitro gastrointestinal digestion. These findings support the possibility of utilizing dairy-derived bioactive peptides in the development of a superior alternative to the current generation of antibacterial and anticancer agents, as well as a functional ingredient in foods, nutraceuticals, and pharmaceuticals. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Identification of CJC-1295, a growth-hormone-releasing peptide, in an unknown pharmaceutical preparation.

Science.gov (United States)

Henninge, John; Pepaj, Milaim; Hullstein, Ingunn; Hemmersbach, Peter

2010-01-01

Several peptide drugs are being manufactured illicitly, and in some cases they are being made available to the public before entering or completing clinical trials. At the request of Norwegian police and customs authorities, unknown pharmaceutical preparations suspected to contain peptide drugs are regularly subjected to analysis. In 2009, an unknown pharmaceutical preparation was submitted for analysis by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS). The preparation was found to contain a 29 amino acid peptide with a C-terminal amide function. Based on the interpretation of mass spectrometric data, an amino acid sequence was proposed. The sequence is consistent with a peptide currently marketed under the name CJC-1295. CJC-1295 is a releasing factor for growth hormone and is therefore considered a Prohibited Substance under Section S2 of the WADA Prohibited List. This substance has potential performance-enhancing effects, it is readily available, and there is reason to believe that it is being used within the bodybuilding community. Copyright © 2010 John Wiley & Sons, Ltd.

Reduction of free fatty acids by acipimox enhances the growth hormone (GH) responses to GH-releasing peptide 2 in elderly men

NARCIS (Netherlands)

Smid, HEC; de Vries, WR; Niesink, M; Bolscher, E; Waasdorp, EJ; Dieguez, C; Casanueva, FF; Koppeschaar, HPF

2000-01-01

GH release is increased by reducing circulating free fatty acids (FFAs). Aging is associated with decreased plasma GH concentrations. We evaluated GH releasing capacity in nine healthy elderly men after administration of GH-releasing peptide 2 (GHRP-2), with or without pretreatment with the

In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle.

Science.gov (United States)

Pohl, M; Collin, E; Bourgoin, S; Clot, A M; Hamon, M; Cesselin, F; Le Bars, D

1992-10-01

The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.

Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro

International Nuclear Information System (INIS)

Saporito, M.S.; Warwick, R.O. Jr.

1989-01-01

We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro. BN and NM-C but not NM-B decreased K + evoked 3 H-5-HT release from superfused HYP slices by 25%. Bacitracin, a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K + evoked 3 H-5-HT release. Phosphoramidon (PAN, 10 μM) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K + evoked 3 H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 μM), enhanced both BN and NM-C inhibition of 3 H-5-HT release. Bestatin (BST, 10 μM) had no effect on BN or NM-C inhibitory activity on 3 H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of 3 H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit 3 H-5-HT uptake

Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

Science.gov (United States)

Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

2016-05-30

The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of Leu-enkephalin and delta sleep inducing peptide (DSIP) on endogenous noradrenaline release by rat brain synaptosomes

International Nuclear Information System (INIS)

Lozhanets, V.V.; Anosov, A.K.

1986-01-01

The nonapeptide delta-sleep inducing peptide (DSIP) causes specific changes in the encephalogram of recipient animals: It prolongs the phase of long-wave or delta sleep. The cellular mechanism of action of DSIP has not yet been explained. To test the hyporhesis that this peptide or its degradation product may be presynaptic regulators of catecholamine release, the action of Leu-enkephaline, DSIP, and amino acids composing DSIP on release of endogenous noradrenalin (NA) from synaptosomes during depolarization was compared. Subcellular fractions from cerebral hemisphere of noninbred male albino rats were isolated. Lactate dehydrogenase activity was determined in the suspension of synaptosomes before and after addition of 0.5% Triton X-100. The results were subjected to statistical analysis, using the Wilcoxon-Mann-Whitney nonparametric test

Steric effects in release of amides from linkers in solid-phase synthesis. Molecular mechanics modeling of key step in peptide and combinatorial chemistry

DEFF Research Database (Denmark)

Norrby, Per-Ola; Jensen, Knud Jørgen

2006-01-01

Acidolytic release of an amide from a solid support by C-N bond cleavage is all ubiquitous and crucial step in many solid-phase syntheses. We have used molecular modeling of a pseudo-equilibrium to explore substituent and steric effects in the release of peptides. The high acid-lability of the ba......Acidolytic release of an amide from a solid support by C-N bond cleavage is all ubiquitous and crucial step in many solid-phase syntheses. We have used molecular modeling of a pseudo-equilibrium to explore substituent and steric effects in the release of peptides. The high acid......-lability of the backbone amide linkage (BAL), which releases sec. amides, compared to C-terminal amide anchoring, which releases primary amides, was rationalized by steric relief upon cleavage. Thus, the relative stability of the carbenium ion formed from the linker in the acidolytic release is an insufficient measure...

Kinetics of immobilisation and release of tryptophan, riboflavin and peptides from whey protein microbeads.

Science.gov (United States)

O'Neill, Graham J; Egan, Thelma; Jacquier, Jean Christophe; O'Sullivan, Michael; Dolores O'Riordan, E

2015-08-01

This study investigated the kinetics of immobilisation and release of riboflavin, amino acids and peptides from whey microbeads. Blank whey microbeads were placed in solutions of the compounds. As the volume of microbeads added to the solution was increased, the uptake of the compounds increased, to a maximum of 95% for the pentapeptide and 56%, 57% and 45% for the dipeptide, riboflavin and tryptophan respectively, however, the rate of uptake remained constant. The rate of uptake increased with increasing molecule hydrophobicity. The opposite was observed in the release studies, the more hydrophobic compounds had lower release rate constants (kr). When whey microbeads are used as sorbents, they show excellent potential to immobilise small hydrophobic molecules and minimise subsequent diffusion, even in high moisture environments. Copyright © 2015 Elsevier Ltd. All rights reserved.

Calcitonin gene-related peptide and somatostatin releases correlated with the area under the lafutidine concentration-time curve in human plasma.

Science.gov (United States)

Ikawa, K; Shimatani, T; Azuma, Y; Inoue, M; Morikawa, N

2006-08-01

To examine the effects of the histamine H(2)-receptor antagonist, lafutidine, at clinical dosage (10 mg tablet after a standardized meal) on plasma levels of the gastrointestinal peptides, calcitonin gene-related peptide (CGRP), somatostatin and gastrin. Six healthy male volunteers ate a standardized meal, and received either lafutidine orally at a dose of 10 mg or water only (control). Blood samples were taken before and up to 4 h after the drug administration. Plasma lafutidine concentrations were determined by high pressure liquid chromatography. Pharmacokinetic analysis of lafutidine was performed using one-compartmental model. The levels of immunoreactive substances of plasma CGRP, somatostatin and gastrin were measured by enzyme immunoassay, and the amount of peptide release was calculated by the trapezoidal method. Lafutidine significantly increased plasma CGRP levels at 1, 1.5, 2.5 and 4 h and the total amount of CGRP release (192 +/- 14.0 pg.h/mL) compared with the control group (128 +/- 21.5 pg.h/mL). Lafutidine significantly increased the plasma somatostatin levels at 1 and 1.5 h, and the total amount of somatostatin released (107 +/- 18.2 pg.h/mL) compared with the control (78.4 +/- 7.70 pg.h/mL). The area under the drug concentration-time curve (AUC) from 0 to 4 h after administration correlated well with the Delta-CGRP and Delta-somatostatin release but not with total amount of gastrin released. However, plasma gastrin levels were significantly elevated at 1.5 h after drug administration. Lafutidine at clinical dosage increases plasma CGRP and the somatostatin. The amounts released correlated with the AUC of lafutidine in humans. These results suggest that the increased release of CGRP and somatostatin may contribute to its gastroprotective and anti-acid secretory effect.

Bioaccessible peptides released by in vitro gastrointestinal digestion of fermented goat milks.

Science.gov (United States)

Moreno-Montoro, Miriam; Jauregi, Paula; Navarro-Alarcón, Miguel; Olalla-Herrera, Manuel; Giménez-Martínez, Rafael; Amigo, Lourdes; Miralles, Beatriz

2018-06-01

In this study, ultrafiltered goat milks fermented with the classical starter bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarus subsp. thermophilus or with the classical starter plus the Lactobacillus plantarum C4 probiotic strain were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and/or high performance liquid chromatography-ion trap (HPLC-IT-MS/MS). Partial overlapping of the identified sequences with regard to fermentation culture was observed. Evaluation of the cleavage specificity suggested a lower proteolytic activity of the probiotic strain. Some of the potentially identified peptides had been previously reported as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, and antibacterial and might account for the in vitro activity previously reported for these fermented milks. Simulated digestion of the products was conducted in the presence of a dialysis membrane to retrieve the bioaccessible peptide fraction. Some sequences with reported physiological activity resisted digestion but were found in the non-dialyzable fraction. However, new forms released by digestion, such as the antioxidant α s1 -casein 144 YFYPQL 149 , the antihypertensive α s2 -casein 90 YQKFPQY 96 , and the antibacterial α s2 -casein 165 LKKISQ 170 , were found in the dialyzable fraction of both fermented milks. Moreover, in the fermented milk including the probiotic strain, the k-casein dipeptidyl peptidase IV inhibitor (DPP-IV) 51 INNQFLPYPY 60 as well as additional ACE inhibitory or antioxidant sequences could be identified. With the aim of anticipating further biological outcomes, quantitative structure activity relationship (QSAR) analysis was applied to the bioaccessible fragments and led to potential ACE inhibitory sequences being proposed. Graphical abstract Ultrafiltered goat milks were fermented with the classical starter bacteria (St) and with St plus the

Neurochemical evidence that cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide modulates the dopaminergic reward system by decreasing the dopamine release in the mouse nucleus accumbens.

Science.gov (United States)

Rakovska, Angelina; Baranyi, Maria; Windisch, Katalin; Petkova-Kirova, Polina; Gagov, Hristo; Kalfin, Reni

2017-09-01

CART (Cocaine- and Amphetamine-Regulated Transcript) peptide is a neurotransmitter naturally occurring in the CNS and found mostly in nucleus accumbens, ventrotegmental area, ventral pallidum, amygdalae and striatum, brain regions associated with drug addiction. In the nucleus accumbens, known for its significant role in motivation, pleasure, reward and reinforcement learning, CART peptide inhibits cocaine and amphetamine-induced dopamine-mediated increases in locomotor activity and behavior, suggesting a CART peptide interaction with the dopaminergic system. Thus in the present study, we examined the effect of CART (55-102) peptide on the basal, electrical field stimulation-evoked (EFS-evoked) (30V, 2Hz, 120 shocks) and returning basal dopamine (DA) release and on the release of the DA metabolites 3,4-dihydroxyphenyl acetaldehyde (DOPAL), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 3,4-dihydroxyphenylethanol (DOPET), 3-methoxytyramine (3-MT) as well as on norepinephrine (NE) and dopamine-o-quinone (Daq) in isolated mouse nucleus accumbens, in a preparation, in which any CART peptide effects on the dendrites or soma of ventral tegmental projection neurons have been excluded. We further extended our study to assess the effect of CART (55-102) peptide on basal cocaine-induced release of dopamine and its metabolites DOPAL, DOPAC, HVA, DOPET and 3-MT as well as on NE and Daq. To analyze the amount of [ 3 H]dopamine, dopamine metabolites, Daq and NE in the nucleus accumbens superfusate, a high-pressure liquid chromatography (HPLC), coupled with electrochemical, UV and radiochemical detections was used. CART (55-102) peptide, 0.1μM, added alone, exerted: (i) a significant decrease in the basal and EFS-evoked levels of extracellular dopamine (ii) a significant increase in the EFS-evoked and returning basal levels of the dopamine metabolites DOPAC and HVA, major products of dopamine degradation and (iii) a significant decrease in the returning basal

Cysteine-stabilised peptide extract of Morinda lucida (Benth) leaf exhibits antimalarial activity and augments antioxidant defense system in P. berghei-infected mice.

Science.gov (United States)

Adebayo, Joseph O; Adewole, Kayode E; Krettli, Antoniana U

2017-07-31

Cysteine-stabilised peptides (CSP) are majorly explored for their bioactivities with applications in medicine and agriculture. Morinda lucida leaf is used indigenously for the treatment of malaria; it also contains CSP but the role of CSP in the antimalarial activity of the leaf has not been evaluated. This study was therefore performed to evaluate the antimalarial activity of partially purified cysteine-stabilised peptide extract (PPCPE) of Morinda lucida leaf and its possible augmentation of the antioxidant systems of liver and erythrocytes in murine malaria. PPCPE was prepared from Morinda lucida leaf. The activity of PPCPE was evaluated in vitro against Plasmodium falciparum W2 and its cytotoxicity against a BGM kidney cell line. PPCPE was also evaluated for its antimalarial activity and its effects on selected liver and erythrocyte antioxidant parameters in P. berghei NK65-infected mice. PPCPE was not active against P. falciparum W2 (IC 50 : >50µg/ml) neither was it cytotoxic (MLD 50 : >1000µg/ml). However, PPCPE was active against P. berghei NK65 in vivo, causing 51.52% reduction in parasitaemia at 31.25mg/Kg body weight on day 4 post-inoculation. PPCPE significantly reduced (P activities of glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase in a dose-dependent manner, which was significant (P antimalarial effect and that PPCPE may augment the antioxidant defense system to alleviate the reactive oxygen species-mediated complications of malaria. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Processing of thyrotropin-releasing hormone prohormone (pro-TRH) generates a biologically active peptide, prepro-TRH-(160-169), which regulates TRH-induced thyrotropin secretion

International Nuclear Information System (INIS)

Bulant, M.; Vaudry, H.; Roussel, J.P.; Astier, H.; Nicolas, P.

1990-01-01

Rat thyrotropin-releasing hormone (TRH) prohormone contains five copies of the TRH progenitor sequence Gln-His-Pro-Gly linked together by connecting sequences whose biological activity is unknown. Both the predicted connecting peptide prepro-TRH-(160-169) (Ps4) and TRH are predominant storage forms of TRH precursor-related peptides in the hypothalamus. To determine whether Ps4 is co-released with TRH, rat median eminence slices were perfused in vitro. Infusion of depolarizing concentrations of KCl induced stimulation of release of Ps4- and TRH-like immunoreactivity. The possible effect of Ps4 on thyrotropin release was investigated in vitro using quartered anterior pituitaries. Infusion of Ps4 alone had no effect on thyrotropin secretion but potentiated TRH-induced thyrotropin release in a dose-dependent manner. In addition, the occurrence of specific binding sites for 125 I-labeled Tyr-Ps4 in the distal lobe of the pituitary was demonstrated by binding analysis and autoradiographic localization. These findings indicate that these two peptides that arise from a single multifunctional precursor, the TRH prohormone, act in a coordinate manner on the same target cells to promote hormonal secretion. These data suggest that differential processing of the TRH prohormone may have the potential to modulate the biological activity of TRH

Release of Periplasmic Nucleotidase Induced by Human Antimicrobial Peptide in E. coli Causes Accumulation of the Immunomodulator Adenosine.

Directory of Open Access Journals (Sweden)

Andreia Bergamo Estrela

Full Text Available Previous work by our group described that human β-defensin-2 induces accumulation of extracellular adenosine (Ado in E. coli cultures through a non-lytic mechanism causing severe plasmolysis. Here, we investigate the presence of AMP as a direct precursor and the involvement of a bacterial enzyme in the generation of extracellular Ado by treated bacteria. Following hBD-2 treatment, metabolites were quantified in the supernatants using targeted HPLC-MS/MS analysis. Microbial growth was monitored by optical density and cell viability was determined by colony forming units counts. Phosphatase activity was measured using chromogenic substrate pNPP. The results demonstrate that defensin-treated E. coli strain W releases AMP in the extracellular space, where it is converted to Ado by a bacterial soluble factor. An increase in phosphatase activity in the supernatant was observed after peptide treatment, similar to the effect of sucrose-induced osmotic stress, suggesting that the periplasmic 5'nucleotidase (5'-NT is released following the plasmolysis event triggered by the peptide. Ado accumulation was enhanced in the presence of Co2+ ion and inhibited by EDTA, further supporting the involvement of a metallo-phosphatase such as 5'-NT in extracellular AMP conversion into Ado. The comparative analysis of hBD-induced Ado accumulation in different E. coli strains and in Pseudomonas aeruginosa revealed that the response is not correlated to the peptide's effect on cell viability, but indicates it might be dependent on the subcellular distribution of the nucleotidase. Taken together, these data shed light on a yet undescribed mechanism of host-microbial interaction: a human antimicrobial peptide inducing selective release of a bacterial enzyme (E. coli 5'-NT, leading to the formation of a potent immunomodulator metabolite (Ado.

The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

Science.gov (United States)

Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

2015-01-01

Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

Cytochalasin B augments diacylglycerol levels in stimulated neutrophils

International Nuclear Information System (INIS)

Honeycutt, P.J.; Niedel, J.

1986-01-01

Diacylglycerol (DG) has gained wide acceptance as an important second messenger and intracellular activator of protein kinase C, but few studies have directly measured DG levels in cells or tissues. The authors measured the mass of DG in lipid extracts from normal human neutrophils by quantitative conversion of DG to [ 32 P] phosphatidic acid using E. coli DG kinase. The chemotactic peptide N-formyl-Met-Leu-Phe (fMLP) stimulated a transient 30% rise in DG that was maximal at 30 to 45 sec and returned to the basal level of 150 picomoles/10 7 cells by one min. This initial peak was followed by a slower, more prolonged 30% increase in DG that was maximal at 20 min. Cytochalasin B (CB) augments many biological responses of neutrophils to fMLP, including superoxide production and lysosomal enzyme release. CB alone caused no change in basal DG levels, but in the presence of CB, fMLP stimulated a rapid, large, and persistent DG response. DG levels increased to 290% of basal at 5 min with a t1/2 = 45 sec. The DG response to fMLP was maximal at 5 to 10 μm CB and 1 μM fMLP. The DG response to optimal fMLP and CB concentrations was decreased 40% by an fMLP antagonist, and no response was elicited by an inactive fMLP analog and CB. Protein kinase C has been implicated in fMLP-stimulated superoxide production and lysosomal enzyme release. These data are consistent with the hypothesis that CB may effect augmentation of biological responses by increasing DG levels

Effects of intranasal and peripheral oxytocin or gastrin-releasing peptide administration on social interaction and corticosterone levels in rats.

Science.gov (United States)

Kent, Pamela; Awadia, Alisha; Zhao, Leah; Ensan, Donna; Silva, Dinuka; Cayer, Christian; James, Jonathan S; Anisman, Hymie; Merali, Zul

2016-02-01

The intranasal route of drug administration has gained increased popularity as it is thought to allow large molecules, such as peptide hormones, more direct access to the brain, while limiting systemic exposure. Several studies have investigated the effects of intranasal oxytocin administration in humans as this peptide is associated with prosocial behavior. There are, however, few preclinical studies investigating the effects of intranasal oxytocin administration in rodents. Oxytocin modulates hypothalamic-pituitary-adrenal (HPA) axis functioning and it has been suggested that oxytocin's ability to increase sociability may occur through a reduction in stress reactivity. Another peptide that appears to influence both social behavior and HPA axis activity is gastrin-releasing peptide (GRP), but it is not known if these GRP-induced effects are related. With this in mind, in the present study, we assessed the effects of intranasal and intraperitoneal oxytocin and GRP administration on social interaction and release of corticosterone in rats. Intranasal and intraperitoneal administration of 20, but not 5 μg, of oxytocin significantly increased social interaction, whereas intranasal and peripheral administration of GRP (20 but not 5 μg) significantly decreased levels of social interaction. In addition, while intranasal oxytocin (20 μg) had no effect on blood corticosterone levels, a marked increase in blood corticosterone levels was observed following intraperitoneal oxytocin administration. With GRP, intranasal (20 μg) but not peripheral administration increased corticosterone levels. These findings provide further evidence that intranasal peptide delivery can induce behavioral alterations in rodents which is consistent with findings from human studies. In addition, the peptide-induced changes in social interaction were not linked to fluctuations in corticosterone levels. Copyright © 2015 Elsevier Ltd. All rights reserved.

Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

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Xue, Deng; Tamai, Riyoko [Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan); Endo, Yasuo [Department of Molecular Regulation, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, Sendai 980-8575 (Japan); Kiyoura, Yusuke [Division of Oral Bacteriology, Department of Oral Medical Science, Ohu University School of Dentistry, 31-1 Misumido, Tomitamachi, Koriyama, Fukushima 963-8611 (Japan)

2009-02-15

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.

Alendronate augments interleukin-1β release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

International Nuclear Information System (INIS)

Deng Xue; Tamai, Riyoko; Endo, Yasuo; Kiyoura, Yusuke

2009-01-01

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1β, but not TNFα, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1β production was inhibited by clodronate. Furthermore, caspase-1, a promoter of IL-1β production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1β induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1β release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs

Peptides in headlock ? a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy

OpenAIRE

Braun, Michael B.; Traenkle, Bjoern; Koch, Philipp A.; Emele, Felix; Weiss, Frederik; Poetz, Oliver; Stehle, Thilo; Rothbauer, Ulrich

2016-01-01

Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a ?-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once boun...

The oncolytic peptide LTX-315 induces cell death and DAMP release by mitochondria distortion in human melanoma cells

Science.gov (United States)

Eike, Liv-Marie; Yang, Nannan; Rekdal, Øystein; Sveinbjørnsson, Baldur

2015-01-01

Host defense peptides (HDPs) are naturally occurring molecules found in most species, in which they play a significant role in the first line defense against intruding pathogens, and several HDPs have been shown to possess anticancer activity. Structure-activity relationship studies on the HDP bovine lactoferricin revealed a de novo design of a nonamer peptide LTX-315, with oncolytic properties. In the present study, we investigated the oncolytic activity of LTX-315 in human melanoma cells (A375). LTX-315 induced a rapid plasma membrane disruption and cell death within 2 hours. At a low concentration, fluorescence-labeled LTX-315 was internalized and accumulated in cytoplasmic vacuoles in close proximity to the mitochondria. The mitochondrial membrane potential was shown to depolarize as a consequence of LTX-315 treatment and at ultrastructural level, the mitochondria morphology was significantly altered. Release of danger signals (DAMPs) such as ATP, Cytochrome C and HMGB1 into the cell supernatant of cultured cells was evident minutes after peptide treatment. The oncolytic effect of LTX-315 involving perturbation of both the cell membrane and the mitochondria with subsequent release of DAMPs may highlight the ability of LTX-315 to induce complete regression and long-term protective immune responses as previously reported in experimental animal models. PMID:26472184

Interactions of GRF(1-29)NH2 with plasma proteins and their effects on the release of the peptide from a PLAGA matrix.

Science.gov (United States)

Mariette, B; Coudane, J; Vert, M

2005-09-02

The administration of the GRF(1-29)NH2 Growth Hormone Releasing Hormone analog is known as relevant of the concept of drug delivery system using a bioresorbable matrix. However, the release of this peptide from poly(dl-lactic acid-co-glycolic acid) matrices is affected by its insolubility at neutral in salted media and in plasma as well. In order to investigate the origin and the nature of the insolubility in these media in more details, the precipitates collected when the peptide was set in contact with saline, isotonic pH=7.4 phosphate buffer and plasma were analyzed by various techniques, namely weighting, gel chromatography, 1D- and 2D-immunoelectrophoresis, and dialysis to discern the soluble from the insoluble or aggregated fractions. It is shown that precipitation in protein-free salted media is due to a salting out phenomenon complemented by the neutralization of the solubilizing electrostatic charges in the isotonic buffer. In contrast, the precipitation in plasma is due to inter polyelectrolyte-type complexation that involved polyanionic proteins having a rather low isoelectric point like albumin, transferin, haptoglobulin and IgG immunoglobulins. When a rather large quantity of GRF(1-29)NH2 was entrapped in bioresorbable pellets working at a percolating regime after subcutaneous implantation in rats, the peptide was slowly released despite the complexation with plasma proteins. However only a very small part of the peptide was found in blood, this small part being still large enough to cause a detectable increase of the circulating growth hormone concentration. Attempts made to increase the solubility of the peptide in plasma were successful when the peptide was combined with arginine, an amino acid known to promote the poor hormonal activity of injected GRF(1-29)NH2 solutions under clinical conditions.

In vitro chemopreventive properties of peptides released from quinoa (Chenopodium quinoa Willd.) protein under simulated gastrointestinal digestion.

Science.gov (United States)

Vilcacundo, Rubén; Miralles, Beatriz; Carrillo, Wilman; Hernández-Ledesma, Blanca

2018-03-01

Because of the continuous and direct interaction between the digestive tract and foods, dietary compounds represent an interesting source of chemopreventive agents for gastrointestinal health. In this study, the influence of a standardized static in vitro gastrointestinal digestion model on the release of peptides with chemopreventive potential from quinoa protein was investigated. Gastroduodenal digests and fractions collected by ultrafiltration were evaluated for their in plate oxygen radical absorbance capacity and in vitro colon cancer cell viability inhibitory activity. Highest effects were observed in the digests obtained during the intestinal phase, with fraction containing peptides 5kDa showing the greatest anti-cancer effects. Seventeen potential bioactive peptides derived from quinoa proteins have been identified. These proteins might be utilized as new ingredients in the development of functional foods or nutraceuticals with the aim of reducing oxidative stress-associated diseases, including cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Enzymatic Release and Characterization of Novel Bioactive Peptides from Milk Proteins

DEFF Research Database (Denmark)

De Gobba, Cristian

-inhibitory, antioxidant and antimicrobial peptides) released from milk proteins by mean of enzyme-catalysed hydrolysis. Goat milk fractions (produced using microfiltration membranes) and bovine casein were used as substrates. The goat milk fractions (retentate, permeate and skimmed milk) were hydrolysed with two...... commercial enzymes. The bovine casein was hydrolysed using the supernatant of a Greenlandic bacterium (Arsukibacterium ikkense), produced in the NOVENIA project, which contains cold-active proteolytic enzymes. The hydrolysates were tested for the relevant bioactivities and active fractions were fractionated...... protein hydrolysates made in other studies. Regarding radical scavenging activity, the bovine casein hydrolysates also showed a positive correlation between extent of hydrolysis and activity, although the difference between the unhydrolysed sample and the hydrolysates was less marked. The goat milk...

Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C-terminal aromatic ring

Czech Academy of Sciences Publication Activity Database

Pražienková, Veronika; Tichá, Anežka; Blechová, Miroslava; Špolcová, Andrea; Železná, Blanka; Maletínská, Lenka

2016-01-01

Roč. 67, č. 1 (2016), s. 121-128 ISSN 0867-5910 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * blood-brain barrier * food intake * lipidization * phenylalanine derivatives Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.883, year: 2016 http://www.jpp.krakow.pl/journal/archive/02_16/articles/11_article.html

Synthesis of peptide thioacids at neutral pH using bis(2-sulfanylethyl)amido peptide precursors.

Science.gov (United States)

Pira, Silvain L; Boll, Emmanuelle; Melnyk, Oleg

2013-10-18

Reaction of bis(2-sulfanylethyl)amido (SEA) peptides with triisopropylsilylthiol in water at neutral pH yields peptide thiocarboxylates. An alkylthioester derived from β-alanine was used to trap the released bis(2-sulfanylethyl)amine and displace the equilibrium toward the peptide thiocarboxylate.

Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

Czech Academy of Sciences Publication Activity Database

Maletínská, L.; Nagelová, V.; Tichá, A.; Zemenová, J.; Pirník, Z.; Holubová, M.; Špolcová, A.; Mikulášková, Barbora; Blechová, M.; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, B.; Kuneš, Jaroslav

2015-01-01

Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA TA ČR(CZ) TE01020028 Institutional support: RVO:67985823 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

Dendroaspis natriuretic peptide binds to the natriuretic peptide clearance receptor

International Nuclear Information System (INIS)

Johns, Douglas G.; Ao, Zhaohui; Heidrich, Bradley J.; Hunsberger, Gerald E.; Graham, Taylor; Payne, Lisa; Elshourbagy, Nabil; Lu, Quinn; Aiyar, Nambi; Douglas, Stephen A.

2007-01-01

Dendroaspis natriuretic peptide (DNP) is a newly-described natriuretic peptide which lowers blood pressure via vasodilation. The natriuretic peptide clearance receptor (NPR-C) removes natriuretic peptides from the circulation, but whether DNP interacts with human NPR-C directly is unknown. The purpose of this study was to test the hypothesis that DNP binds to NPR-C. ANP, BNP, CNP, and the NPR-C ligands AP-811 and cANP(4-23) displaced [ 125 I]-ANP from NPR-C with pM-to-nM K i values. DNP displaced [ 125 I]-ANP from NPR-C with nM potency, which represents the first direct demonstration of binding of DNP to human NPR-C. DNP showed high pM affinity for the GC-A receptor and no affinity for GC-B (K i > 1000 nM). DNP was nearly 10-fold more potent than ANP at stimulating cGMP production in GC-A expressing cells. Blockade of NPR-C might represent a novel therapeutic approach in augmenting the known beneficial actions of DNP in cardiovascular diseases such as hypertension and heart failure

Omega-conotoxin- and nifedipine-insensitive voltage-operated calcium channels mediate K(+)-induced release of pro-thyrotropin-releasing hormone-connecting peptides Ps4 and Ps5 from perifused rat hypothalamic slices.

Science.gov (United States)

Valentijn, K; Tranchand Bunel, D; Vaudry, H

1992-07-01

The rat thyrotropin-releasing hormone (TRH) precursor (prepro-TRH) contains five copies of the TRH progenitor sequence linked together by intervening sequences. Recently, we have shown that the connecting peptides prepro-TRH-(160-169) (Ps4) and prepro-TRH-(178-199) (Ps5) are released from rat hypothalamic neurones in response to elevated potassium concentrations, in a calcium-dependent manner. In the present study, the role of voltage-operated calcium channels in potassium-induced release of Ps4 and Ps5 was investigated, using a perifusion system for rat hypothalamic slices. The release of Ps4 and Ps5 stimulated by potassium (70 mM) was blocked by the inorganic ions Co2+ (2.6 mM) and Ni2+ (5 mM). In contrast, the stimulatory effect of KCl was insensitive to Cd2+ (100 microM). The dihydropyridine antagonist nifedipine (10 microM) had no effect on K(+)-evoked release of Ps4 and Ps5. Furthermore, the response to KCl was not affected by nifedipine (10 microM) in combination with diltiazem (1 microM), a benzothiazepine which increases the affinity of dihydropyridine antagonists for their receptor. The dihydropyridine agonist BAY K 8644, at concentrations as high as 1 mM, did not stimulate the basal secretion of Ps4 and Ps5. In addition, BAY K 8644 had no potentiating effect on K(+)-induced release of Ps4 and Ps5. The marine cone snail toxin omega-conotoxin, a blocker of both L- and N-type calcium channels had no effect on the release of Ps4 and Ps5 stimulated by potassium. Similarly, the omega-conopeptide SNX-111, a selective blocker of N-type calcium channels, did not inhibit the stimulatory effect of potassium. The release of Ps4 and Ps5 evoked by high K+ was insensitive to the non-selective calcium channel blocker verapamil (20 microM). Amiloride (1 microM), a putative blocker of T-type calcium channels, did not affect KCl-induced secretion of the two connecting peptides. Taken together, these results indicate that two connecting peptides derived from the pro-TRH, Ps

Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

DEFF Research Database (Denmark)

Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina

2010-01-01

This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5 g...... intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4+/-0.5 mM in the first 90 min (period 1) and raised 1.5 times the fasting...

Growth hormone (GH)-releasing activity of chicken GH-releasing hormone (GHRH) in chickens.

Science.gov (United States)

Harvey, S; Gineste, C; Gaylinn, B D

2014-08-01

Two peptides with sequence similarities to growth hormone releasing hormone (GHRH) have been identified by analysis of the chicken genome. One of these peptides, chicken (c) GHRH-LP (like peptide) was previously found to poorly bind to chicken pituitary membranes or to cloned and expressed chicken GHRH receptors and had little, if any, growth hormone (GH)-releasing activity in vivo or in vitro. In contrast, a second more recently discovered peptide, cGHRH, does bind to cloned and expressed cGHRH receptors and increases cAMP activity in transfected cells. The possibility that this peptide may have in vivo GH-releasing activity was therefore assessed. The intravenous (i.v.) administration of cGHRH to immature chickens, at doses of 3-100 μg/kg, significantly increased circulating GH concentrations within 10 min of injection and the plasma GH levels remained elevated for at least 30 min after the injection of maximally effective doses. The plasma GH responses to cGHRH were comparable with those induced by human (h) or porcine (p) GHRH preparations and to that induced by thyrotropin releasing hormone (TRH). In marked contrast, the i.v. injection of cGHRH-LP had no significant effect on circulating GH concentrations in immature chicks. GH release was also increased from slaughterhouse chicken pituitary glands perifused for 5 min with cGHRH at doses of 0.1 μg/ml or 1.0 μg/ml, comparable with GH responses to hGHRH1-44. In contrast, the perifusion of chicken pituitary glands with cGHRH-LP had no significant effect on GH release. In summary, these results demonstrate that cGHRH has GH-releasing activity in chickens and support the possibility that it is the endogenous ligand of the cGHRH receptor. Copyright © 2014 Elsevier Inc. All rights reserved.

Bone induction through controlled release of novel BMP-2-related peptide from PTMC11-F127-PTMC11 hydrogels

International Nuclear Information System (INIS)

Tang Shuo; Li Jingfeng; Teng Yu; Guo Xiaodong; Zhao Jingjing; Xu Shuyun; Quan Daping

2012-01-01

Bone morphogenetic protein 2 (BMP-2) is the most powerful osteogenic factor; its effectiveness in enhancing osteoblastic activation has been confirmed both in vitro and in vivo. We developed a novel peptide (designated P24) derived from the ‘knuckle’ epitope of BMP-2 and found it also had osteogenic bioactivity to some extent. The main objective of this study was to develop a controlled release system based on poly(trimethylene carbonate)–F127–poly(trimethylene carbonate) (PTMC 11 -F127-PTMC 11 ) hydrogels for the P24 peptide, to promote bone formation. By varying the copolymer concentrations, we demonstrated that P24/PTMC 11 -F127-PTMC 11 hydrogels were an efficient system for the sustained release of P24 over 21–35 days. The P24-loaded hydrogels elevated alkaline phosphatase activity and promoted the expression of osteocalcin mRNA in bone marrow stromal cells (BMSCs) in vitro. Radiographic and histological examination showed that P24-loaded hydrogels could induce more effective ectopic bone formation in vivo than P24-free hydrogels. These results indicate that the PTMC 11 -F127-PTMC 11 hydrogel is a suitable carrier for the controlled release of P24, and is a promising injectable biomaterial for the induction of bone regeneration. (paper)

C peptide and insulin releasing RIA test for the investigation of β cell function in diabetic patients

International Nuclear Information System (INIS)

Shi Ailan; Zhu Chengmo; Wang Qiyu; Wang Ping

1993-01-01

Results of C-peptide releasing RIA test in 15 normals, and 100 diabetes were summarized and compared with glucose tolerance test and serum insulin for investigating the characteristics in different types of diabetes and evaluating the functional state of islet β cell. In 36 cases of IDDM the fasting blood sugar was significantly increased, and further elevated after eating of bread, but its peak time delay in 2 hours (normalin 1 hour). The level of basal C-peptide is very low, but shows slightly weak on no response after bread stimulating test, all of this denotes that β cell function of islets severely injured. The increasing of fasting blood sugar in 64 cases of NIDDM was lower than those of IDDM. Fasting C-peptide and insulin was normal or increased, their peak value increased after bread stimulation with peak time delayed also at 2 hours. Above results demonstrated that the function of islets B cell decreased but not fully deprived. It is concluded that C-peptide and insulin stimulating test, together with OGTT can accurately assess the islets β cell function, and also have important significance in the pathogenesis, classification and staging, prognostic evaluation and monitoring of therapeutic effects in diabetes

Obesity augments the age-induced increase in mitochondrial capacity for H(2) O(2) release in Zucker fatty rats

DEFF Research Database (Denmark)

Hey-Mogensen, Martin; Jeppesen, Jacob; Madsen, K

2012-01-01

determined and related to citrate synthase activity to determine intrinsic mitochondrial function. Mitochondrial-specific super-oxide dismuthase (MnSOD) protein content was determined in isolated mitochondria and muscle homogenate. Catalase protein content was determined in muscle homogenate. Results: Young...... was associated with increased mitochondrial hydrogenperoxide release. MnSOD tended to be higher in the obese strain in the isolated mitochondria. Regardless of age, catalase protein content was significantly lower in the obese rats. Conclusions: This study shows that the augmented increase in obesity and insulin...

Corticotropin-releasing factor peptide antagonists: design, characterization and potential clinical relevance.

Science.gov (United States)

Rivier, Jean E; Rivier, Catherine L

2014-04-01

Elusive for more than half a century, corticotropin-releasing factor (CRF) was finally isolated and characterized in 1981 from ovine hypothalami and shortly thereafter, from rat brains. Thirty years later, much has been learned about the function and localization of CRF and related family members (Urocortins 1, 2 and 3) and their 2 receptors, CRF receptor type 1 (CRFR1) and CRF receptor type 2 (CRFR2). Here, we report the stepwise development of peptide CRF agonists and antagonists, which led to the CRFR1 agonist Stressin1; the long-acting antagonists Astressin2-B which is specific for CRFR2; and Astressin B, which binds to both CRFR1 and CRFR2.This analog has potential for the treatment of CRF-dependent diseases in the periphery, such as irritable bowel syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Circulating levels of cholecystokinin and gastrin-releasing peptide in rainbow trout fed different diets.

Science.gov (United States)

Jönsson, Elisabeth; Forsman, Antti; Einarsdottir, Ingibjörg E; Egnér, Barbro; Ruohonen, Kari; Björnsson, Björn Thrandur

2006-09-01

Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal peptides thought to be important regulators of intake and digestion of food in vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of homologous radioimmunoassays, and the hormonal levels assessed in relation to dietary lipid:protein ratio and food intake. Fish were acclimated to either a high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio-dense lead-glass beads were included in the diets for assessment of feed intake. Fish were terminally sampled for blood and stomach contents prior to feeding at time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL diet. Plasma CCK levels were not affected by the amount of food ingested. GRP levels in plasma were not influenced by sampling time, diet, or feed intake. The results indicate that the endocrine release of gastrointestinal CCK is increased during feeding and may be further influenced by the dietary lipid:protein ratio in rainbow trout. Plasma GRP levels, on the other hand, appear not to be influenced by feeding or diet composition.

LC-MS/MS analysis of lipidized analogs of prolactin-releasing peptide utilizing a monolithic column and simple sample preparation

Czech Academy of Sciences Publication Activity Database

Zemenová, Jana; Sýkora, D.; Freislebenová, A.; Maletínská, Lenka

2017-01-01

Roč. 9, č. 17 (2017), s. 1319-1328 ISSN 1757-6180 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : LC-MS * lipopeptides * monolithic column * prolactin-releasing peptide * stability Subject RIV: CE - Biochemistry OBOR OECD: Biochemical research methods Impact factor: 2.673, year: 2016

Developing a Dissociative Nanocontainer for Peptide Drug Delivery

Directory of Open Access Journals (Sweden)

Patrick Kelly

2015-10-01

Full Text Available The potency, selectivity, and decreased side effects of bioactive peptides have propelled these agents to the forefront of pharmacological research. Peptides are especially promising for the treatment of neurological disorders and pain. However, delivery of peptide therapeutics often requires invasive techniques, which is a major obstacle to their widespread application. We have developed a tailored peptide drug delivery system in which the viral capsid of P22 bacteriophage is modified to serve as a tunable nanocontainer for the packaging and controlled release of bioactive peptides. Recent efforts have demonstrated that P22 nanocontainers can effectively encapsulate analgesic peptides and translocate them across blood-brain-barrier (BBB models. However, release of encapsulated peptides at their target site remains a challenge. Here a Ring Opening Metathesis Polymerization (ROMP reaction is applied to trigger P22 nanocontainer disassembly under physiological conditions. Specifically, the ROMP substrate norbornene (5-Norbornene-2-carboxylic acid is conjugated to the exterior of a loaded P22 nanocontainer and Grubbs II Catalyst is used to trigger the polymerization reaction leading to nanocontainer disassembly. Our results demonstrate initial attempts to characterize the ROMP-triggered release of cargo peptides from P22 nanocontainers. This work provides proof-of-concept for the construction of a triggerable peptide drug delivery system using viral nanocontainers.

Expression of gastrin-releasing peptide by excitatory interneurons in the mouse superficial dorsal horn.

Science.gov (United States)

Gutierrez-Mecinas, Maria; Watanabe, Masahiko; Todd, Andrew J

2014-12-11

Gastrin-releasing peptide (GRP) and its receptor have been shown to play an important role in the sensation of itch. However, although GRP immunoreactivity has been detected in the spinal dorsal horn, there is debate about whether this originates from primary afferents or local excitatory interneurons. We therefore examined the relation of GRP immunoreactivity to that seen with antibodies that label primary afferent or excitatory interneuron terminals. We tested the specificity of the GRP antibody by preincubating with peptides with which it could potentially cross-react. We also examined tissue from a mouse line in which enhanced green fluorescent protein (EGFP) is expressed under control of the GRP promoter. GRP immunoreactivity was seen in both primary afferent and non-primary glutamatergic axon terminals in the superficial dorsal horn. However, immunostaining was blocked by pre-incubation of the antibody with substance P, which is present at high levels in many nociceptive primary afferents. EGFP+ cells in the GRP-EGFP mouse did not express Pax2, and their axons contained the vesicular glutamate transporter 2 (VGLUT2), indicating that they are excitatory interneurons. In most cases, their axons were also GRP-immunoreactive. Multiple-labelling immunocytochemical studies indicated that these cells did not express either of the preprotachykinin peptides, and that they generally lacked protein kinase Cγ, which is expressed by a subset of the excitatory interneurons in this region. These results show that GRP is expressed by a distinct population of excitatory interneurons in laminae I-II that are likely to be involved in the itch pathway. They also suggest that the GRP immunoreactivity seen in primary afferents in previous studies may have resulted from cross-reaction of the GRP antibody with substance P or the closely related peptide neurokinin A.

Glutamine reduces postprandial glycemia and augments the glucagon-like peptide-1 response in type 2 diabetes patients

DEFF Research Database (Denmark)

Samocha-Bonet, Dorit; Wong, Olivia; Synnott, Emma-Leigh

2011-01-01

Impaired glucagon-like peptide (GLP-1) secretion or response may contribute to ineffective insulin release in type 2 diabetes. The conditionally essential amino acid glutamine stimulates GLP-1 secretion in vitro and in vivo. In a randomized, crossover study, we evaluated the effect of oral...... glutamine, with or without sitagliptin (SIT), on postprandial glycemia and GLP-1 concentration in 15 type 2 diabetes patients (glycated hemoglobin 6.5 ± 0.6%). Participants ingested a low-fat meal (5% fat) after receiving either water (control), 30 g l-glutamine (Gln-30), 15 g L-glutamine (Gln-15), 100 mg...... concentration and limiting postprandial glycemia in type 2 diabetes....

Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

Czech Academy of Sciences Publication Activity Database

Mikulášková, Barbora; Zemenová, Jana; Pirník, Zdenko; Pražienková, Veronika; Bednárová, Lucie; Železná, Blanka; Maletínská, Lenka; Kuneš, Jaroslav

2016-01-01

Roč. 75, Jan (2016), s. 109-117 ISSN 0196-9781 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : prolactin-releasing peptide * lipidization * food intake * c-Fos * pharmacokinetics * CD spectroscopy Subject RIV: CE - Biochemistry Impact factor: 2.778, year: 2016

Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide

OpenAIRE

Daniela I. Pérez Sirkin; Daniela I. Pérez Sirkin; Anne-Gaëlle Lafont; Nédia Kamech; Gustavo M. Somoza; Paula G. Vissio; Paula G. Vissio; Sylvie Dufour

2017-01-01

GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide onl...

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

International Nuclear Information System (INIS)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas

2011-01-01

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses

Carbohydrate Mimetic Peptides Augment Carbohydrate-Reactive Immune Responses in the Absence of Immune Pathology

Energy Technology Data Exchange (ETDEWEB)

Hennings, Leah; Artaud, Cecile; Jousheghany, Fariba; Monzavi-Karbassi, Behjatolah; Pashov, Anastas; Kieber-Emmons, Thomas, E-mail: tke@uams.edu [Winthrop P. Rockefeller Cancer Institute and Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR 72205 (United States)

2011-11-11

Among the most challenging of clinical targets for cancer immunotherapy are Tumor Associated Carbohydrate Antigens (TACAs). To augment immune responses to TACA we are developing carbohydrate mimetic peptides (CMPs) that are sufficiently potent to activate broad-spectrum anti-tumor reactivity. However, the activation of immune responses against terminal mono- and disaccharide constituents of TACA raises concerns regarding the balance between “tumor destruction” and “tissue damage”, as mono- and disaccharides are also expressed on normal tissue. To support the development of CMPs for clinical trial testing, we demonstrate in preclinical safety assessment studies in mice that vaccination with CMPs can enhance responses to TACAs without mediating tissue damage to normal cells expressing TACA. BALB/c mice were immunized with CMPs that mimic TACAs reactive with Griffonia simplicifolia lectin 1 (GS-I), and tissue reactivity of serum antibodies were compared with the tissue staining profile of GS-I. Tissues from CMP immunized mice were analyzed using hematoxylin and eosin stain, and Luxol-fast blue staining for myelination. Western blots of membranes from murine mammary 4T1 cells, syngeneic with BALB/c mice, were also compared using GS-I, immunized serum antibodies, and naive serum antibodies. CMP immunization enhanced glycan reactivities with no evidence of pathological autoimmunity in any immunized mice demonstrating that tissue damage is not an inevitable consequence of TACA reactive responses.

Glucagon-like peptide 1--a cardiologic dimension

DEFF Research Database (Denmark)

Treiman, Marek; Elvekjaer, Mikkel; Engstrøm, Thomas

2010-01-01

Recent experimental data suggest glucagon-like peptide 1 (GLP-1) and its analogs to have direct effects on the cardiovascular system, in addition to their classic glucoregulatory actions. These direct effects may be cardioprotective, contractility augmenting, and vasorelaxant. A few preliminary c...

Glucagon-like peptide-1 analogues: An overview

Directory of Open Access Journals (Sweden)

Vishal Gupta

2013-01-01

Full Text Available Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia and suppression of glucagon (fasting hyperglycemia, amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly, DPP-4-resistant analogues (lixisenatide, albiglutide, and analogues of human GLP-1 (liraglutide, taspoglutide. Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

Novel lipidized analogs of prolactin-releasing peptide have prolonged half-lives and exert anti-obesity effects after peripheral administration

Czech Academy of Sciences Publication Activity Database

Maletínská, Lenka; Nagelová, Veronika; Tichá, Anežka; Zemenová, Jana; Pirník, Zdenko; Holubová, Martina; Špolcová, Andrea; Mikulášková, Barbora; Blechová, Miroslava; Sýkora, D.; Lacinová, Z.; Haluzík, M.; Železná, Blanka; Kuneš, Jaroslav

2015-01-01

Roč. 39, č. 6 (2015), s. 986-993 ISSN 0307-0565 R&D Projects: GA ČR GAP303/10/1368; GA ČR GAP303/12/0576; GA TA ČR(CZ) TE01020028 Institutional support: RVO:61388963 Keywords : food intake * prolactin-releasing peptide * GPR10 receptor Subject RIV: CE - Biochemistry Impact factor: 5.337, year: 2015

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

International Nuclear Information System (INIS)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.; Pierre, Philippe; Chadee, Deborah N.; Pizza, Francis X.

2015-01-01

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

Energy Technology Data Exchange (ETDEWEB)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T. [Department of Kinesiology, The University of Toledo, Toledo, OH (United States); Pierre, Philippe [Centre d’Immunologie de Marseille-Luminy U2M, Aix-Marseille Université, Marseille (France); INSERM U631, Institut National de la Santé et Recherche Médicale, Marseille (France); CNRS UMR6102, Centre National de la Recherche Scientifique, Marseille (France); Chadee, Deborah N. [Department of Biological Sciences, The University of Toledo, Toledo, OH (United States); Pizza, Francis X., E-mail: Francis.Pizza@utoledo.edu [Department of Kinesiology, The University of Toledo, Toledo, OH (United States)

2015-02-15

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation, myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through

Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

Czech Academy of Sciences Publication Activity Database

Mikulášková, Barbora; Zemenová, J.; Pirník, Z.; Pražienková, V.; Bednárová, L.; Železná, B.; Maletínská, L.; Kuneš, Jaroslav

2016-01-01

Roč. 75, Jan (2016), s. 109-117 ISSN 0196-9781 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:67985823 Keywords : prolactin-releasing peptide * lipidization * food intake * c-Fos * pharmacokinetics * CD spectroscopy Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.778, year: 2016

Oleic acid stimulates glucagon-like peptide-1 release from enteroendocrine cells by modulating cell respiration and glycolysis.

Science.gov (United States)

Clara, Rosmarie; Langhans, Wolfgang; Mansouri, Abdelhak

2016-03-01

Glucagon-like peptide-1 (GLP-1) is a potent satiating and incretin hormone released by enteroendocrine L-cells in response to eating. Dietary fat, in particular monounsaturated fatty acids, such as oleic acid (OA), potently stimulates GLP-1 secretion from L-cells. It is, however, unclear whether the intracellular metabolic handling of OA is involved in this effect. First we determined the optimal medium for the bioenergetics measurements. Then we examined the effect of OA on the metabolism of the immortalized enteroendocrine GLUTag cell model and assessed GLP-1 release in parallel. We measured oxygen consumption rate and extracellular acidification rate in response to OA and to different metabolic inhibitors with the Seahorse extracellular flux analyzer. OA increased cellular respiration and potently stimulated GLP-1 release. The fatty acid oxidation inhibitor etomoxir did neither reduce OA-induced respiration nor affect the OA-induced GLP-1 release. In contrast, inhibition of the respiratory chain or of downstream steps of aerobic glycolysis reduced the OA-induced GLP-1 release, and an inhibition of the first step of glycolysis by addition of 2-deoxy-d-glucose even abolished it. These findings indicate that an indirect stimulation of glycolysis is crucial for the OA-induced release of GLP-1. Copyright © 2015 Elsevier Inc. All rights reserved.

PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from human airway smooth muscle cells

Directory of Open Access Journals (Sweden)

Halayko Andrew J

2009-09-01

Full Text Available Abstract Background Airway smooth muscle contributes to the pathogenesis of pulmonary diseases by secreting inflammatory mediators such as interleukin-8 (IL-8. IL-8 production is in part regulated via activation of Gq-and Gs-coupled receptors. Here we study the role of the cyclic AMP (cAMP effectors protein kinase A (PKA and exchange proteins directly activated by cAMP (Epac1 and Epac2 in the bradykinin-induced IL-8 release from a human airway smooth muscle cell line and the underlying molecular mechanisms of this response. Methods IL-8 release was assessed via ELISA under basal condition and after stimulation with bradykinin alone or in combination with fenoterol, the Epac activators 8-pCPT-2'-O-Me-cAMP and Sp-8-pCPT-2'-O-Me-cAMPS, the PKA activator 6-Bnz-cAMP and the cGMP analog 8-pCPT-2'-O-Me-cGMP. Where indicated, cells were pre-incubated with the pharmacological inhibitors Clostridium difficile toxin B-1470 (GTPases, U0126 (extracellular signal-regulated kinases ERK1/2 and Rp-8-CPT-cAMPS (PKA. The specificity of the cyclic nucleotide analogs was confirmed by measuring phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein. GTP-loading of Rap1 and Rap2 was evaluated via pull-down technique. Expression of Rap1, Rap2, Epac1 and Epac2 was assessed via western blot. Downregulation of Epac protein expression was achieved by siRNA. Unpaired or paired two-tailed Student's t test was used. Results The β2-agonist fenoterol augmented release of IL-8 by bradykinin. The PKA activator 6-Bnz-cAMP and the Epac activator 8-pCPT-2'-O-Me-cAMP significantly increased bradykinin-induced IL-8 release. The hydrolysis-resistant Epac activator Sp-8-pCPT-2'-O-Me-cAMPS mimicked the effects of 8-pCPT-2'-O-Me-cAMP, whereas the negative control 8-pCPT-2'-O-Me-cGMP did not. Fenoterol, forskolin and 6-Bnz-cAMP induced VASP phosphorylation, which was diminished by the PKA inhibitor Rp-8-CPT-cAMPS. 6-Bnz-cAMP and 8-pCPT-2'-O-Me-cAMP induced GTP

Binding free energy and counterion release for adsorption of the antimicrobial peptide lactoferricin B on a POPG membrane

Science.gov (United States)

Tolokh, Igor S.; Vivcharuk, Victor; Tomberli, Bruno; Gray, C. G.

2009-09-01

Molecular dynamics (MD) simulations are used to study the interaction of an anionic palmitoyl-oleoyl-phosphatidylglycerol (POPG) bilayer with the cationic antimicrobial peptide bovine lactoferricin (LFCinB) in a 100 mM NaCl solution at 310 K. The interaction of LFCinB with a POPG bilayer is employed as a model system for studying the details of membrane adsorption selectivity of cationic antimicrobial peptides. Seventy eight 4 ns MD production run trajectories of the equilibrated system, with six restrained orientations of LFCinB at 13 different separations from the POPG membrane, are generated to determine the free energy profile for the peptide as a function of the distance between LFCinB and the membrane surface. To calculate the profile for this relatively large system, a variant of constrained MD and thermodynamic integration is used. A simplified method for relating the free energy profile to the LFCinB-POPG membrane binding constant is employed to predict a free energy of adsorption of -5.4±1.3kcal/mol and a corresponding maximum adsorption binding force of about 58 pN. We analyze the results using Poisson-Boltzmann theory. We find the peptide-membrane attraction to be dominated by the entropy increase due to the release of counterions and polarized water from the region between the charged membrane and peptide, as the two approach each other. We contrast these results with those found earlier for adsorption of LFCinB on the mammalianlike palmitoyl-oleoyl-phosphatidylcholine membrane.

Effect of processing on polyamine content and bioactive peptides released after in vitro gastrointestinal digestion of infant formulas.

Science.gov (United States)

Gómez-Gallego, C; Recio, I; Gómez-Gómez, V; Ortuño, I; Bernal, M J; Ros, G; Periago, M J

2016-02-01

This study examined the influence of processing on polyamines and peptide release after the digestion of a commercial infant formula designed for children during the first months of life. Polyamine oxidase activity was not suppressed during the manufacturing process, which implicates that polyamine concentrations were reduced over time and during infant formula self-life. In gel electrophoresis, in vitro gastrointestinal digestion of samples with reduced amount of enzymes and time of digestion shows an increase in protein digestibility, reflected in the increase in nonprotein nitrogen after digestion and the disappearance of β-lactoglobulin and α-lactalbumin bands in gel electrophoresis. Depending on the sample, between 22 and 87 peptides were identified after gastrointestinal digestion. A peptide from β-casein f(98-105) with the sequence VKEAMAPK and antioxidant activity appeared in all of the samples. Other peptides with antioxidant, immunomodulatory, and antimicrobial activities were frequently found, which could have an effect on infant health. The present study confirms that the infant formula manufacturing process determines the polyamine content and peptidic profile after digestion of the infant formula. Because compositional dissimilarity between human milk and infant formula in polyamines and proteins could be responsible for some of the differences in health reported between breast-fed and formula-fed children, these changes must be taken into consideration because they may have a great effect on infant nutrition and development. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Evaluation of the antioxidant activity in food model system of fish peptides released during simulated gastrointestinal digestion

DEFF Research Database (Denmark)

Nieva-Echevarria, B.; Jacobsen, Charlotte; García Moreno, Pedro Jesús

In the last decade, increasing evidences of the occurrence of lipid oxidation during digestion have been reported, in either in vivo or in vitro studies (1,2,3). As a result, the nutritional quality and safety of foodstuffs could be affected by the decrease of certain lipidic compounds of interest...... in the gastrointestinal tract. In fact, several studies have reported antioxidant activity of fish protein hydrolysates, coming from fish industry waste by-products (3,4). Thus, the potential release of peptides showing antioxidant properties during fish digestion cannot be ruled out. In order to shed light...... on these aspects, in vitro digestates of European sea bass were submitted to ultrafiltration using membranes with different cut off size. Afterwards, the potential antioxidant activity of the peptide fractions obtained was evaluated by comparing the oxidative stability of fish oil-in-water emulsions (5...

Peripheral administration of palmitoylated prolactin-releasing peptide induces Fos expression in hypothalamic neurons involved in energy homeostasis in NMRI male mice

Czech Academy of Sciences Publication Activity Database

Pirník, Zdenko; Železná, Blanka; Kiss, A.; Maletínská, Lenka

2015-01-01

Roč. 1625, Nov 2 (2015), s. 151-158 ISSN 0006-8993 R&D Projects: GA ČR(CZ) GA15-08679S Institutional support: RVO:61388963 Keywords : hypothalamus * prolactin-releasing peptide * Fos * oxytocin * hypocretin * mice Subject RIV: CE - Biochemistry Impact factor: 2.561, year: 2015

Conformational Aspects of High Content Packing of Antimicrobial Peptides in Polymer Microgels

DEFF Research Database (Denmark)

Singh, Shalini; Datta, Aritreyee; Borro, Bruno C

2017-01-01

Successful use of microgels as delivery systems of antimicrobial peptides (AMPs) requires control of factors determining peptide loading and release to/from the microgels as well as of membrane interactions of both microgel particles and released peptides. Addressing these, we here investigate ef...

High-frequency stimulation-induced peptide release synchronizes arcuate kisspeptin neurons and excites GnRH neurons

Science.gov (United States)

Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Padilla, Stephanie L; Palmiter, Richard D

2016-01-01

Kisspeptin (Kiss1) and neurokinin B (NKB) neurocircuits are essential for pubertal development and fertility. Kisspeptin neurons in the hypothalamic arcuate nucleus (Kiss1ARH) co-express Kiss1, NKB, dynorphin and glutamate and are postulated to provide an episodic, excitatory drive to gonadotropin-releasing hormone 1 (GnRH) neurons, the synaptic mechanisms of which are unknown. We characterized the cellular basis for synchronized Kiss1ARH neuronal activity using optogenetics, whole-cell electrophysiology, molecular pharmacology and single cell RT-PCR in mice. High-frequency photostimulation of Kiss1ARH neurons evoked local release of excitatory (NKB) and inhibitory (dynorphin) neuropeptides, which were found to synchronize the Kiss1ARH neuronal firing. The light-evoked synchronous activity caused robust excitation of GnRH neurons by a synaptic mechanism that also involved glutamatergic input to preoptic Kiss1 neurons from Kiss1ARH neurons. We propose that Kiss1ARH neurons play a dual role of driving episodic secretion of GnRH through the differential release of peptide and amino acid neurotransmitters to coordinate reproductive function. DOI: http://dx.doi.org/10.7554/eLife.16246.001 PMID:27549338

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

OpenAIRE

Andreas Bayer; Justus Lammel; Mersedeh Tohidnezhad; Sebastian Lippross; Peter Behrendt; Tim Klüter; Thomas Pufe; Jochen Cremer; Holger Jahr; Franziska Rademacher; Regine Gläser; Jürgen Harder

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF?)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting acti...

Thrust augmentation for a small turbojet engine

OpenAIRE

Hackaday, Gary L.

1999-01-01

Approved for public release; distribution is unlimited A Sophia J450 (nine pounds of thrust) gas turbine engine was used first to examine the thrust augmentation generated using an ejector shroud. Experimental results obtained with and without the ejector were compared with performance predicted using an engine code and a one-dimensional ejector analysis. The engine code was revised to incorporate a radial turbine and the correct compressor map. Thrust augmentation of 3-10% was measured an...

Endogenous opioid peptides as neurotransmitters in the rat hippocampus

International Nuclear Information System (INIS)

Neumaier, J.F.

1989-01-01

The role of endogenous opioid peptides as neurotransmitters in the rat hippocampus was investigated by using extracellular recording and radioligand binding techniques in the hippocampal slice preparation. Synaptic conductances from endogenously released opioid peptides have been difficult to detect. This problem was approach by designing a novel assay of opioid peptide release, in which release was detected by measuring binding competition between endogenous opioids and added radioligand. Membrane depolarization displaced [ 3 H]-diprenorphine binding in a transient, calcium-dependent, and peptidase-sensitive manner. Autoradiographic localization of the sites of [ 3 H]-diprenorphine binding displacement showed that significant opioid peptide release and receptor occupancy occurred in each major subregion of the hippocampal slices. This assay method can not be used to define optimal electrical stimulation conditions for releasing endogenous opioids. The binding displacement method was extended to the study of the sigma receptor. Depolarization of hippocampal slices was found to reduce the binding of the sigma-selective radioligand [ 3 H]-ditolylguanidine in a transient and calcium-dependent manner with no apparent direct effects on sigma receptor affinity

Augmented internalisation of ferroportin to late endosomes impairs iron uptake by enterocyte-like IEC-6 cells.

Science.gov (United States)

Oates, Phillip S; Thomas, Carla

2005-08-01

Absorption of iron occurs by duodenal enterocytes, involving uptake by the divalent metal transporter-1 (DMT1) and release by ferroportin. Ferroportin responds to the hepatocyte-produced 25-amino-acid-peptide hepcidin-25 by undergoing internalisation to late endosomes that impair iron release. Ferroportin is also expressed on the apical membrane of polarised Caco-2 cells, rat intestinal cells and in IEC-6 cells (an intestinal epithelial cell line). A blocking antibody to ferroportin also impairs the uptake, but not the release, of iron. In this study IEC-6 cells were used to study the mechanism of impairment or recovery from impairment produced by the blocking antibody and the fate of DMT1 and ferroportin. Uptake of 1 muM Fe(II) was studied by adding the antibody from time 0 and after adding or removing the antibody once a steady state had been reached. Surface binding, maximum iron transport rate V(max) and transporter affinity (K(m)) were measured after impairment of iron uptake. Ferroportin and DMT1 distribution were assessed by immunofluorescence microscopy. Antibody-mediated impairment, or recovery from impairment, of Fe(II) uptake occurred within minutes. Impairment was lost when the antibody was combined with the immunizing peptide. DMT1 and ferroportin undergo internalisation to late endosomes and, in the presence of the antibody, augmented internalisation of DMT1 and ferroportin caused swelling of late endosomes. Surface binding of Fe(II) and iron transport V(max) were reduced by 50%, indicating that the antibody removed membrane-bound DMT1. The ferroportin antibody induced rapid turnover of membrane ferroportin and DMT1 and its internalisation to late endosomes, resulting in impaired Fe(II) uptake.

Peptides in headlock--a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy.

Science.gov (United States)

Braun, Michael B; Traenkle, Bjoern; Koch, Philipp A; Emele, Felix; Weiss, Frederik; Poetz, Oliver; Stehle, Thilo; Rothbauer, Ulrich

2016-01-21

Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a β-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once bound, the peptide is fastened by two nanobody side chains that clamp it in a headlock fashion. Exploiting this unusual binding mode, we generated a novel nanobody-derived capture and detection system. Matrix-coupled nanobody enables the fast and efficient isolation of epitope-tagged proteins from prokaryotic and eukaryotic expression systems. Additionally, the fluorescently labeled nanobody visualizes subcellular structures in different cellular compartments. The high-affinity-binding and modifiable peptide tag of this system renders it a versatile and robust tool to combine biochemical analysis with microscopic studies.

Aptamer based peptide enrichment for quantitative analysis of gonadotropin-releasing hormone by LC-MS/MS.

Science.gov (United States)

Richards, S L; Cawley, A T; Cavicchioli, R; Suann, C J; Pickford, R; Raftery, M J

2016-04-01

Over recent years threats to racing have expanded to include naturally occurring biological molecules, such as peptides and proteins, and their synthetic analogues. Traditionally, antibodies have been used to enable detection of these compounds as they allow purification and concentration of the analyte of interest. The rapid expansion of peptide-based therapeutics necessitates a similarly rapid development of suitable antibodies or other means of enrichment. Potential alternative enrichment strategies include the use of aptamers, which offer the significant advantage of chemical synthesis once the nucleic acid sequence is known. A method was developed for the enrichment, detection and quantitation of gonadotropin-releasing hormone (GnRH) in equine urine using aptamer-based enrichment and LC-MS/MS. The method achieved comparable limits of detection (1 pg/mL) and quantification (2.5 pg/mL) to previously published antibody-based enrichment methods. The intra- and inter-assay precision achieved was less than 10% at both 5 and 20 pg/mL, and displayed a working dynamic range of 2.5-100 pg/mL. Significant matrix enhancement (170 ± 8%) and low analytical recovery (29 ± 15%) was observed, although the use of an isotopically heavy labelled GnRH peptide, GnRH (Pro(13)C5,(15)N), as the internal standard provides compensation for these parameters. Within the current limits of detection GnRH was detectable up to 1h post administration in urine and identification of a urinary catabolite extended this detection window to 4h. Based on the results of this preliminary investigation we propose the use of aptamers as a viable alternative to antibodies in the enrichment of peptide targets from equine urine. Copyright © 2016 Elsevier B.V. All rights reserved.

CXCL10 Controls Inflammatory Pain via Opioid Peptide-Containing Macrophages in Electroacupuncture

Science.gov (United States)

Wang, Ying; Gehringer, Rebekka; Mousa, Shaaban A.; Hackel, Dagmar; Brack, Alexander; Rittner, Heike L.

2014-01-01

Acupuncture is widely used for pain treatment in patients with osteoarthritis or low back pain, but molecular mechanisms remain largely enigmatic. In the early phase of inflammation neutrophilic chemokines direct opioid-containing neutrophils in the inflamed tissue and stimulate opioid peptide release and antinociception. In this study the molecular pathway and neuroimmune connections in complete Freund's adjuvant (CFA)-induced hind paw inflammation and electroacupuncture for peripheral pain control were analyzed. Free moving Wistar rats with hind paw inflammation were treated twice with electroacupuncture at GB30 (Huan Tiao - gall bladder meridian) (day 0 and 1) and analyzed for mechanical and thermal nociceptive thresholds. The cytokine profiles as well as the expression of opioid peptides were quantified in the inflamed paw. Electroacupuncture elicited long-term antinociception blocked by local injection of anti-opioid peptide antibodies (beta-endorphin, met-enkephalin, dynorphin A). The treatment altered the cytokine profile towards an anti-inflammatory pattern but augmented interferon (IFN)-gamma and the chemokine CXCL10 (IP-10: interferon gamma-inducible protein) protein and mRNA expression with concomitant increased numbers of opioid peptide-containing CXCR3+ macrophages. In rats with CFA hind paw inflammation without acupuncture repeated injection of CXCL10 triggered opioid-mediated antinociception and increase opioid-containing macrophages. Conversely, neutralization of CXCL10 time-dependently decreased electroacupuncture-induced antinociception and the number of infiltrating opioid peptide-expressing CXCR3+ macrophages. In summary, we describe a novel function of the chemokine CXCL10 - as a regulator for an increase of opioid-containing macrophages and antinociceptive mediator in inflammatory pain and as a key chemokine regulated by electroacupuncture. PMID:24732949

Composite augmentation phalloplasty: personal experience after 275 patients

Directory of Open Access Journals (Sweden)

Juan Monreal

2015-03-01

Full Text Available Aim: To report the author's experience in augmentation phalloplasty by studying a retrospective series of patients who underwent fat grafting for girth enhancement or a composite technique based on suspensory ligament release plus fat grafting performed simultaneously. Methods: The author analyzed retrospectively the outcomes of 275 augmentation phalloplasty procedures performed in 259 patients until November 2013. Of these, 127 correspond to girth augmentation with fat grafting and 148 to composite augmentation phalloplasty (girth augmentation with fat grafting and length improvement by suspensory ligament release. In 16 patients girth and length enhancement were performed in two separate procedures. Results: Of this 259 patients, 87 underwent postoperative follow-up for at least 12 months and 160 patients underwent follow-up for at least 6 months. The average increase in circumference at 6 months was 1.7 cm (1.57 cm at 12 months and the average increase in length of 3.2 cm (3.1 cm at 12 months. Twenty-two patients showed minor complications that were treated without sequelae and without influencing the final result. Conclusion: By judicious use of currently available techniques, it is possible to achieve stable increases in penis size. The use of composite techniques provides better final results than the use of individual techniques performed alone due to the increase of the actual volume of the penis. An adequate informed consent is essential in all patients due to the unrealistic expectations expressed by the majority of them.

APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

Directory of Open Access Journals (Sweden)

Hilla Fogel

2014-06-01

Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

D-2 dopamine receptor activation reduces free [3H]arachidonate release induced by hypophysiotropic peptides in anterior pituitary cells

International Nuclear Information System (INIS)

Canonico, P.L.

1989-01-01

Dopamine reduces the stimulation of intracellular [ 3 H]arachidonate release produced by the two PRL-stimulating peptides angiotensin-II and TRH. This effect is concentration dependent and is mediated by stimulation of D-2 dopamine receptors. D-2 receptor agonists (bromocriptine, dihydroergocryptine, and dihydroergocristine) inhibit the release of fatty acid induced by angiotensin-II with a potency that parallels their ability to inhibit PRL release in vitro. Conversely, the selective D-2 receptor antagonist L-sulpiride completely prevents dopamine's effect, whereas SCH 23390 (a D-1 receptor antagonist) is ineffective. The inhibitory action of dopamine does not seem to be consequent to an action on the adenylate cyclase-cAMP system, as 8-bromo-cAMP (1 mM) does not affect either basal or dopamine-inhibited [ 3 H]arachidonate release. However, a 24-h pertussis toxin pretreatment significantly reduces the action of dopamine on fatty acid release. Collectively, these results suggest that D-2 dopamine receptor-mediated inhibition of intracellular [ 3 H]arachidonate release requires the action of a GTP-binding protein, but is not a consequence of an inhibitory action on cAMP levels

Controlled long-term release of small peptide hormones using a new microporous polypropylene polymer: its application for vasopressin in the Brattleboro rat and potential perinatal use

International Nuclear Information System (INIS)

Kruisbrink, J.; Boer, G.J.

1984-01-01

Based on drug release by microporous hollow fibers and the recent introduction of microporous polymers, a new technique was developed for controlled delivery of peptides. Small-diameter microporous polypropylene tubing, lumen-loaded with microgram quantities of vasopressin, and coated with collodion, releases vasopressin after in vitro immersion slowly (1-100 ng/d) and constantly for months. The mechanism of pseudo-zero-order delivery is based on high adsorption of vasopressin, keeping the void volume concentration of dissolved vasopressin constant, which is consequently a constant driving force of outward diffusion. The collodion coating prevents the entry of proteinaceous compounds which would result in rapid desorption of vasopressin. The present delivery module provides a lasting release for other peptides as well (lysine-vasopressin, oxytocin, alpha-melanocyte-stimulating hormone and, to a lesser extent, Met-enkephalin). The microporous polymer-collodion device is biocompatible and, loaded with vasopressin, successfully alleviates the diabetes insipidus of Brattleboro rats deficient for vasopressin. Subcutaneous implantation normalized diuresis for a period of 60 d and constant urine vasopressin excretion is observed. When the commercially available osmotic minipump is too large for implantation, the small size of the present controlled-delivery system allows peptide treatment of young and immature laboratory rats, even if located in utero

Secretion of intact proteins and peptide fragments by lysosomal pathways of protein degradation

International Nuclear Information System (INIS)

Isenman, L.D.; Dice, J.F.

1989-01-01

We report that degradation of proteins microinjected into human fibroblasts is accompanied by release into the culture medium of peptide fragments and intact proteins as well as single amino acids. For the nine proteins and polypeptides microinjected, acid-precipitable radioactivity, i.e. peptide fragments and/or intact proteins, ranged from 10 to 67% of the total released radioactivity. Peptide fragments and/or intact protein accounted for 60% of the radioactivity released into the medium by cells microinjected with ribonuclease A. Two major radiolabeled peptide fragments were found, and one was of an appropriate size to function as an antigen in antigen-presenting cells. The peptides released from microinjected ribonuclease A were derived from lysosomal pathways of proteolysis based on several lines of evidence. Previous studies have shown that microinjected ribonuclease A is degraded to single amino acids entirely within lysosomes. We show that release of free amino acids and peptide fragments and/or intact protein was equivalently stimulated by serum deprivation and equivalently inhibited by NH4Cl. We also show that lysosomal degradation of endocytosed [3H]ribonuclease A was accompanied by the release of two peptide fragments similar in size and charge to those from microinjected [ 3 H]ribonuclease A. These findings demonstrate that degradation within lysosomes occurs in a manner that spares specific peptides; they also suggest a previously unsuspected pathway by which cells can secrete cytosol-derived polypeptides

Peptides in headlock – a novel high-affinity and versatile peptide-binding nanobody for proteomics and microscopy

Science.gov (United States)

Braun, Michael B.; Traenkle, Bjoern; Koch, Philipp A.; Emele, Felix; Weiss, Frederik; Poetz, Oliver; Stehle, Thilo; Rothbauer, Ulrich

2016-01-01

Nanobodies are highly valuable tools for numerous bioanalytical and biotechnical applications. Here, we report the characterization of a nanobody that binds a short peptide epitope with extraordinary affinity. Structural analysis reveals an unusual binding mode where the extended peptide becomes part of a β-sheet structure in the nanobody. This interaction relies on sequence-independent backbone interactions augmented by a small number of specificity-determining side chain contacts. Once bound, the peptide is fastened by two nanobody side chains that clamp it in a headlock fashion. Exploiting this unusual binding mode, we generated a novel nanobody-derived capture and detection system. Matrix-coupled nanobody enables the fast and efficient isolation of epitope-tagged proteins from prokaryotic and eukaryotic expression systems. Additionally, the fluorescently labeled nanobody visualizes subcellular structures in different cellular compartments. The high-affinity-binding and modifiable peptide tag of this system renders it a versatile and robust tool to combine biochemical analysis with microscopic studies. PMID:26791954

Effects of long-term treatment with growth hormone-releasing peptide-2 in the GHRH knockout mouse.

Science.gov (United States)

Alba, Maria; Fintini, Danilo; Bowers, Cyril Y; Parlow, A F; Salvatori, Roberto

2005-11-01

Growth hormone (GH) secretagogues (GHS) stimulate GH secretion in vivo in humans and in animals. They act on the ghrelin receptor, expressed in both the hypothalamus and the pituitary. It is unknown whether GHSs act predominantly by increasing the release of hypothalamic GH-releasing hormone (GHRH) or by acting directly on the somatotroph cells. We studied whether a potent GHS could stimulate growth in the absence of endogenous GHRH. To this end, we used GHRH knockout (GHRH-KO) mice. These animals have proportionate dwarfism due to severe GH deficiency (GHD) and pituitary hypoplasia due to reduced somatotroph cell mass. We treated male GHRH-KO mice for 6 wk (from week 1 to week 7 of age) with GH-releasing peptide-2 (GHRP-2, 10 microg s.c. twice a day). Chronic treatment with GHRP-2 failed to stimulate somatotroph cell proliferation and GH secretion and to promote longitudinal growth. GHRP-2-treated mice showed an increase in total body weight compared with placebo-treated animals, due to worsening of the body composition alterations typical of GHD animals. These data demonstrate that GHRP-2 failed to reverse the severe GHD caused by lack of GHRH.

The Gastrin-Releasing Peptide Receptor as Target for Molecular Imaging of Prostate Cancer : GRPR expression in prostate cancer and targeting with Bombesin-like radiopharmaceuticals

NARCIS (Netherlands)

Ananias, Hildo

2014-01-01

Prostaatkanker is wereldwijd een veel voorkomende oorzaak van kanker, morbiditeit en sterfte. Nauwkeurige stagering is moeilijk en nog steeds suboptimaal. De Gastrin-Releasing Peptide Receptor (GRPR) is een tumor-geassocieerd antigeen dat tot overexpressie wordt gebracht in prostaatkanker. Gerichte

Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I.

Science.gov (United States)

van Ree, R; Aalberse, R C

1995-03-01

The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.

Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

DEFF Research Database (Denmark)

Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jørgensen, Nils Bruun

2013-01-01

Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones...

SHP-1, a novel peptide isolated from seahorse inhibits collagen release through the suppression of collagenases 1 and 3, nitric oxide products regulated by NF-kappaB/p38 kinase.

Science.gov (United States)

Ryu, BoMi; Qian, Zhong-Ji; Kim, Se-Kwon

2010-01-01

Considerable efforts have been taken to identify natural peptides as potential bioactive substances. In this study, novel peptide (SHP-1) derived from seahorse (Hippocampus, Syngnathidae) hydrolysate was explored for its inhibitory effects on collagen release in arthritis with the investigation of its underlying mechanism of action. The efficacy of SHP-1 was determined on cartilage protective effects such as inhibition of collagen and GAG release. SHP-1 was able to suppress not only the expression of collagenases 1 and 3, but also the production of NO via down-regulation of iNOS. However, it presented an irrelevant effect on the level of GAG release in chondrocytic and osteoblastic cells. Inhibition of collagen release by SHP-1 is associated with restraining the phosphorylation of NF-kappaB and p38 kinase cascade. Therefore, it could be suggested that SHP-1 has a potential to be used in arthritis treatment.

Presenilin 2 is the predominant γ-secretase in microglia and modulates cytokine release.

Directory of Open Access Journals (Sweden)

Suman Jayadev

2010-12-01

Full Text Available Presenilin 1 (PS1 and Presenilin 2 (PS2 are the enzymatic component of the γ-secretase complex that cleaves amyloid precursor protein (APP to release amyloid beta (Aβ peptide. PS deficiency in mice results in neuroinflammation and neurodegeneration in the absence of accumulated Aβ. We hypothesize that PS influences neuroinflammation through its γ-secretase action in CNS innate immune cells. We exposed primary murine microglia to a pharmacological γ-secretase inhibitor which resulted in exaggerated release of TNFα and IL-6 in response to lipopolysaccharide. To determine if this response was mediated by PS1, PS2 or both we used shRNA to knockdown each PS in a murine microglia cell line. Knockdown of PS1 did not lead to decreased γ-secretase activity while PS2 knockdown caused markedly decreased γ-secretase activity. Augmented proinflammatory cytokine release was observed after knockdown of PS2 but not PS1. Proinflammatory stimuli increased microglial PS2 gene transcription and protein in vitro. This is the first demonstration that PS2 regulates CNS innate immunity. Taken together, our findings suggest that PS2 is the predominant γ-secretase in microglia and modulates release of proinflammatory cytokines. We propose PS2 may participate in a negative feedback loop regulating inflammatory behavior in microglia.

Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling

NARCIS (Netherlands)

Gosens, Reinout; Bos, I.S.; Zaagsma, Hans; Meurs, Herman

2005-01-01

Rationale: Recent findings have demonstrated that muscarinic M-3 receptor stimulation enhances airway smooth muscle proliferation to peptide growth factors in vitro. Because both peptide growth factor expression and acetylcholine release are known to be augmented in allergic airway inflammation, it

Antimicrobial Peptides in 2014

Directory of Open Access Journals (Sweden)

Guangshun Wang

2015-03-01

Full Text Available This article highlights new members, novel mechanisms of action, new functions, and interesting applications of antimicrobial peptides reported in 2014. As of December 2014, over 100 new peptides were registered into the Antimicrobial Peptide Database, increasing the total number of entries to 2493. Unique antimicrobial peptides have been identified from marine bacteria, fungi, and plants. Environmental conditions clearly influence peptide activity or function. Human α-defensin HD-6 is only antimicrobial under reduced conditions. The pH-dependent oligomerization of human cathelicidin LL-37 is linked to double-stranded RNA delivery to endosomes, where the acidic pH triggers the dissociation of the peptide aggregate to release its cargo. Proline-rich peptides, previously known to bind to heat shock proteins, are shown to inhibit protein synthesis. A model antimicrobial peptide is demonstrated to have multiple hits on bacteria, including surface protein delocalization. While cell surface modification to decrease cationic peptide binding is a recognized resistance mechanism for pathogenic bacteria, it is also used as a survival strategy for commensal bacteria. The year 2014 also witnessed continued efforts in exploiting potential applications of antimicrobial peptides. We highlight 3D structure-based design of peptide antimicrobials and vaccines, surface coating, delivery systems, and microbial detection devices involving antimicrobial peptides. The 2014 results also support that combination therapy is preferred over monotherapy in treating biofilms.

Evidence that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from isolated intestine.

Science.gov (United States)

Vizi, E S; Somogyi, G T; Magyar, K

1981-12-01

1 The release of acetylcholine from guinea-pig ileal isolated longitudinal muscle strip with intact Auerbach's plexus was measured by bioassay and by a radioisotope technique. 2 Normorphine (5 x 10(-7)M) and D-Met2, Pro5-enkephalinamide (D-Met, Pro-EA) reduced the release of acetylcholine. Theophylline, an adenosine antagonist, failed to prevent the inhibitory effect of normorphine or D-Met, Pro-EA. 3 Theophylline (1.7 x 10(-4)M) by itself enhanced the twitch responses to field stimulation (0.1 Hz) but did not prevent the inhibitory effect of normorphine and D-Met, Pro-EA. 4 From the results it can be concluded that morphine and opioid peptides do not share a common pathway with adenosine in inhibiting acetylcholine release from axon terminals of Auerbach's plexus.

Measurement of Nonribosomal Peptide Synthetase Adenylation Domain Activity Using a Continuous Hydroxylamine Release Assay.

Science.gov (United States)

Duckworth, Benjamin P; Wilson, Daniel J; Aldrich, Courtney C

2016-01-01

Adenylation is a crucial enzymatic process in the biosynthesis of nonribosomal peptide synthetase (NRPS) derived natural products. Adenylation domains are considered the gatekeepers of NRPSs since they select, activate, and load the carboxylic acid substrate onto a downstream peptidyl carrier protein (PCP) domain of the NRPS. We describe a coupled continuous kinetic assay for NRPS adenylation domains that substitutes the PCP domain with hydroxylamine as the acceptor molecule. The pyrophosphate released from the first-half reaction is then measured using a two-enzyme coupling system, which detects conversion of the chromogenic substrate 7-methylthioguanosine (MesG) to 7-methylthioguanine. From profiling substrate specificity of unknown or engineered adenylation domains to studying chemical inhibition of adenylating enzymes, this robust assay will be of widespread utility in the broad field NRPS enzymology.

Improving Peptide Applications Using Nanotechnology.

Science.gov (United States)

Narayanaswamy, Radhika; Wang, Tao; Torchilin, Vladimir P

2016-01-01

Peptides are being successfully used in various fields including therapy and drug delivery. With advancement in nanotechnology and targeted delivery carrier systems, suitable modification of peptides has enabled achievement of many desirable goals over-riding some of the major disadvantages associated with the delivery of peptides in vivo. Conjugation or physical encapsulation of peptides to various nanocarriers, such as liposomes, micelles and solid-lipid nanoparticles, has improved their in vivo performance multi-fold. The amenability of peptides to modification in chemistry and functionalization with suitable nanocarriers are very relevant aspects in their use and have led to the use of 'smart' nanoparticles with suitable linker chemistries that favor peptide targeting or release at the desired sites, minimizing off-target effects. This review focuses on how nanotechnology has been used to improve the number of peptide applications. The paper also focuses on the chemistry behind peptide conjugation to nanocarriers, the commonly employed linker chemistries and the several improvements that have already been achieved in the areas of peptide use with the help of nanotechnology.

Octopus gonadotrophin-releasing hormone: a multifunctional peptide in the endocrine and nervous systems of the cephalopod.

Science.gov (United States)

Minakata, H; Shigeno, S; Kano, N; Haraguchi, S; Osugi, T; Tsutsui, K

2009-03-01

The optic gland, which is analogous to the anterior pituitary in the context of gonadal maturation, is found on the upper posterior edge of the optic tract of the octopus Octopus vulgaris. In mature octopus, the optic glands enlarge and secrete a gonadotrophic hormone. A peptide with structural features similar to that of vertebrate gonadotrophin-releasing hormone (GnRH) was isolated from the brain of octopus and was named oct-GnRH. Oct-GnRH showed luteinising hormone-releasing activity in the anterior pituitary cells of the Japanese quail Coturnix coturnix. Oct-GnRH immunoreactive signals were observed in the glandular cells of the mature optic gland. Oct-GnRH stimulated the synthesis and release of sex steroids from the ovary and testis, and elicited contractions of the oviduct. Oct-GnRH receptor was expressed in the gonads and accessory organs, such as the oviduct and oviducal gland. These results suggest that oct-GnRH induces the gonadal maturation and oviposition by regulating sex steroidogenesis and a series of egg-laying behaviours via the oct-GnRH receptor. The distribution and expression of oct-GnRH in the central and peripheral nervous systems suggest that oct-GnRH acts as a multifunctional modulatory factor in feeding, memory processing, sensory, movement and autonomic functions.

Genetic induction of the gastrin releasing peptide receptor on tumor cells for radiolabeled peptide binding

International Nuclear Information System (INIS)

Raben, David; Stackhouse, Murray; Buchsbaum, Donald J.; Mikheeva, Galeena; Khazaeli, M.B.; McLean, Stephanie; Kirkman, Richard; Krasnykh, Victor; Curiel, David T.

1996-01-01

Purpose/Objective: To improve upon existing radioimmunotherapy (RAIT) approaches, we have devised a strategy to genetically induce high levels of new membrane-associated receptors on human cancer cells targetable by radiolabeled peptides. In this context, we report successful adenoviral-mediated transduction of tumor cells to express the murine gastrin releasing peptide receptor (mGRPr) as demonstrated by 125 I-labeled bombesin binding. Materials and Methods: To demonstrate the feasibility of our strategy and to provide rapid proof of principle, we constructed a plasmid encoding the mGRPr gene. We cloned the mGRPr gene into the adenoviral shuttle vector pACMVpLpARS+ (F. Graham). We then utilized the methodology of adenovirus-polylysine-mediated transfection (AdpLmGRPr) to accomplish transient gene expression of mGRPr in two human cancer cell lines including A427 non-small cell lung cancer cells and HeLa cervical cancer cells. Murine GRPr expression was then measured by a live-cell binding assay using 125 I-labeled bombesin. In order to develop this strategy further, it was necessary to construct a vector that would be more efficient for in vivo transduction. In this regard, we constructed a recombinant adenoviral vector (AdCMVGRPr) encoding the mGRPr under the control of the CMV promoter based on in vivo homologous recombination methods. The recombinant shuttle vector containing mGRPr was co-transfected with the adenoviral rescue plasmid pJM17 into the E1A trans complementing cell line 293 allowing for derivation of replication-incompetent, recombinant adenoviral vector. Individual plaques were isolated and subjected to two further rounds of plaque purification. The identity of the virus was confirmed at each step by PCR employing primers for mGRPr. The absence of wild-type adenovirus was confirmed by PCR using primers to the adenoviral E1A gene. SKOV3.ip1 human ovarian cancer cells and MDA-MB-231 human breast cancer cells were transduced in vitro with AdCMVGRPr at

Light-modulated release of RFamide-like neuropeptides from nervus terminalis axon terminals in the retina of goldfish.

Science.gov (United States)

Fischer, A J; Stell, W K

1997-03-01

The nervus terminalis of teleosts, a cranial nerve anatomically associated with the olfactory system, projects to visual system targets including retina and optic tectum. It is known to contain gonadotropin-releasing hormone and RFamide-like peptides, but its function remains unknown. We have probed nervus terminalis function in goldfish by measuring peptide content in retina and tectum with a radioimmunoassay for A18Famide (neuropeptide AF; bovine morphine-modulating peptide). We found that retinal peptide content increased in the dark and decreased in the light, whereas tectal peptide content decreased in the dark and increased in the light. In addition, RFamide-like peptide content in the retina was transiently decreased by severing both olfactory tracts, increased in light-adapted eyes treated with a GABAergic agonist (isoguvacine), and decreased in dark-adapted eyes treated with GABAergic antagonists (bicuculline and picrotoxin). We also found that RFamide-like peptide release could be induced in dark-adapted isolated-superfused retinas by exposure to light or a high concentration (102.5 mM) of potassium ions. We interpret the increase and decrease in peptide content as reflecting a decrease and increase, respectively, in rate of peptide release. We propose that the release and accumulation of RFamide-like peptides in axon terminals of nervus terminalis processes in the retina are modulated primarily by neurons intrinsic to the retina and regulated by light. Peptide release appears to be inhibited tonically in the dark by GABA acting through GABAA receptors; light facilitates peptide release by disinhibition due to a reduction in GABA release. In addition, we propose that electrical signals originating outside the retina can override these intrinsic release-modulating influences.

The Equine PeptideAtlas

DEFF Research Database (Denmark)

Bundgaard, Louise; Jacobsen, Stine; Sørensen, Mette Aamand

2014-01-01

Progress in MS-based methods for veterinary research and diagnostics is lagging behind compared to the human research, and proteome data of domestic animals is still not well represented in open source data repositories. This is particularly true for the equine species. Here we present a first...... Equine PeptideAtlas encompassing high-resolution tandem MS analyses of 51 samples representing a selection of equine tissues and body fluids from healthy and diseased animals. The raw data were processed through the Trans-Proteomic Pipeline to yield high quality identification of proteins and peptides....... The current release comprises 24 131 distinct peptides representing 2636 canonical proteins observed at false discovery rates of 0.2% at the peptide level and 1.4% at the protein level. Data from the Equine PeptideAtlas are available for experimental planning, validation of new datasets, and as a proteomic...

Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects.

Science.gov (United States)

Berlanga-Acosta, Jorge; Abreu-Cruz, Angel; Herrera, Diana García-Del Barco; Mendoza-Marí, Yssel; Rodríguez-Ulloa, Arielis; García-Ojalvo, Ariana; Falcón-Cama, Viviana; Hernández-Bernal, Francisco; Beichen, Qu; Guillén-Nieto, Gerardo

2017-01-01

Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs' binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of "drugable" peptides awaits for a definitive clinical niche.

Synthetic Cationic Peptide IDR-1002 Provides Protection against Bacterial Infections through Chemokine Induction and Enhanced Leukocyte Recruitment

DEFF Research Database (Denmark)

Nijnik, Anastasia; Madera, Laurence; Ma, Shuhua

2010-01-01

and the PI3K, NF-κB, and MAPK signaling pathways. The protective activity of the peptide was associated with in vivo augmentation of chemokine production and recruitment of neutrophils and monocytes to the site of infection. These results highlight the importance of the chemokine induction activity of host...... defense peptides and demonstrate that the optimization of the ex vivo chemokine-induction properties of peptides is a promising method for the rational development of immunomodulatory IDR peptides with enhanced anti-infective activity....

Quantification of peptides released during in vitro digestion of cooked meat.

Science.gov (United States)

Sayd, T; Chambon, C; Santé-Lhoutellier, V

2016-04-15

We aimed to identify and quantify the peptides generated during in vitro digestion of cooked meat by liquid chromatography coupled with high resolution mass spectrometer. A total of 940 non-redundant peptides in the gastric compartment and 989 non-redundant peptides in the intestinal compartment were quantified and identified. Among the 71 different proteins identified, 43 meat proteins were found in the two digestive compartments, 20 proteins were specific to the gastric compartment and 8 proteins to the intestinal compartment. In terms of estimation, the proteins involved in muscle contraction and structure were preferentially enzymatically hydrolyzed in the small intestine. The effect of cooking provided different but less clear patterns of digestion. To the best of our knowledge, this constitutes the highest number of peptides identified in beef meat digests and provides a comprehensive database for meat protein digestion associated with cooking conditions. Such quantitative and qualitative differences may have important nutritional consequences. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation of collagen peptide functionalized chitosan nanoparticles by ionic gelation method: An effective carrier system for encapsulation and release of doxorubicin for cancer drug delivery

Energy Technology Data Exchange (ETDEWEB)

Anandhakumar, S., E-mail: rsanandhakumar@gmail.com [SRM Research Institute, SRM University, Kattankulathur, Chennai 603203 (India); Krishnamoorthy, G.; Ramkumar, K.M. [SRM Research Institute, SRM University, Kattankulathur, Chennai 603203 (India); Raichur, A.M. [Department of Materials Engineering, Indian Institute of Science, Bangalore 560012 (India)

2017-01-01

In recent years, nanoparticles (NPs) based on biopolymers or peptides are gaining popularity for the encapsulation and release of drug molecules, especially for cancer therapy, due to their ability for targeted and controlled release. The use of collagen peptide (CP) for the preparation of chitosan (CN) NPs is especially interesting as it results in NPs that are stable under physiological conditions. In this work, mono-dispersed pH responsive CPCN NPs of about 100 nm were prepared via ionic gelation method by simple and mild co-precipitation of CN and CP. Investigation of NPs with Fourier transform infra-red (FTIR) spectroscopy and dynamic light scattering (DLS) measurements reveals that hydrogen bonding and electrostatic interactions are believed to be major driving forces for NP formation and drug encapsulation, respectively. Scanning electron microscopic (SEM) investigations show that hard and fine CPCN NPs transform to soft and bigger gel like particles as a function of collagen concentration. The unique “polymeric gel” structure of NPs showed high encapsulation efficiency towards doxorubicin hydrochloride (DOX) as well as pH controlled release. Anti-proliferative and cell viability analysis revealed that DOX loaded NPs showed excellent anti-proliferative characteristics against HeLa cells with favorable biocompatibility against normal cells. Such NPs have high potential for use as smart drug delivery carriers in advanced cancer therapy. - Highlights: • Preparation of collagen peptide functionalized chitosan nanoparticles • Hydrogen bonding plays a key role in particle formation. • Electrostatic interaction plays a key role in drug encapsulation. • Functionalized chitosan particles are more stable than chitosan NPs.

Bio-fabrication and physiological self-release of tissue equivalents using smart peptide amphiphile templates.

Science.gov (United States)

Gouveia, Ricardo M; Hamley, Ian W; Connon, Che J

2015-10-01

In this study we applied a smart biomaterial formed from a self-assembling, multi-functional synthetic peptide amphiphile (PA) to coat substrates with various surface chemistries. The combination of PA coating and alignment-inducing functionalised substrates provided a template to instruct human corneal stromal fibroblasts to adhere, become aligned and then bio-fabricate a highly-ordered, multi-layered, three-dimensional tissue by depositing an aligned, native-like extracellular matrix. The newly-formed corneal tissue equivalent was subsequently able to eliminate the adhesive properties of the template and govern its own complete release via the action of endogenous proteases. Tissues recovered through this method were structurally stable, easily handled, and carrier-free. Furthermore, topographical and mechanical analysis by atomic force microscopy showed that tissue equivalents formed on the alignment-inducing PA template had highly-ordered, compact collagen deposition, with a two-fold higher elastic modulus compared to the less compact tissues produced on the non-alignment template, the PA-coated glass. We suggest that this technology represents a new paradigm in tissue engineering and regenerative medicine, whereby all processes for the bio-fabrication and subsequent self-release of natural, bio-prosthetic human tissues depend solely on simple template-tissue feedback interactions.

Solid lipid particles for oral delivery of peptide and protein drugs III - the effect of fed state conditions on the in vitro release and degradation of desmopressin

DEFF Research Database (Denmark)

Christophersen, Philip C; Vaghela, Dimple; Müllertz, Anette

2014-01-01

The effect of food intake on the release and degradation of peptide drugs from solid lipid particles is unknown and was therefore investigated in vitro using different fed state media in a lipolysis model. Desmopressin was used as a model peptide and incorporated into solid lipid particles...... and the protease or desmopressin. Addition of a medium chain triglyceride, trilaurin, in combination with drug-loaded lipid particles diminished the food effect on the TG18 particles, and trilaurin is therefore proposed to be a suitable excipient for reduction of the food effect. Overall, the present study shows...... that strategies to reduce food effect, such as adding trilaurin, for lipid particle formulations should be considered as drug release from such formulations might be influenced by the presence of food in the gastrointestinal tract....

In vitro evaluation of (99m)Tc-EDDA/tricine-HYNIC-Q-Litorin in gastrin-releasing peptide receptor positive tumor cell lines.

Science.gov (United States)

Yurt Lambrecht, Fatma; Durkan, Kübra; Ozgür, Aykut; Gündüz, Cumhur; Avcı, Cığır Biray; Susluer, Sunde Yılmaz

2013-05-01

Bombesin and its derivatives exhibit a high affinity for gastrin-releasing peptide receptor (GRPr), which is over-expressed in a variety of human cancers (prostate, pancreatic, lung, etc.). The aim of this study was to investigate the in vitro potential of the hydrazinonicotinamide (HYNIC)-Q-Litorin. (99m)Tc labeling was performed by using different co-ligands: tricine and ethylenediamine diacetic acid (EDDA). The radiochemical stability of radiolabeled peptide conjugates was checked at room temperature and in cysteine solution up to 24 h. The in vitro cell uptake of (99m)Tc-EDDA-HYNIC-Q-Litorin and (99m)Tc-tricine-HYNIC-Q-Litorin were evaluated on pancreatic tumor and control cell lines. Optimum specific activity and incubation time were determined for all the cell lines. The results showed that the cell uptake of the radiolabeled peptide conjugates in tumor cell lines were higher than in the control cell line. The findings of this study indicated the need for further development of in vivo study as a radiopharmaceutical for pancreatic tumor imaging.

Monitoring multiple myeloma by idiotype-specific peptide binders of tumor-derived exosomes.

Science.gov (United States)

Iaccino, Enrico; Mimmi, Selena; Dattilo, Vincenzo; Marino, Fabiola; Candeloro, Patrizio; Di Loria, Antonio; Marimpietri, Danilo; Pisano, Antonio; Albano, Francesco; Vecchio, Eleonora; Ceglia, Simona; Golino, Gaetanina; Lupia, Antonio; Fiume, Giuseppe; Quinto, Ileana; Scala, Giuseppe

2017-10-13

Tumor-derived exosomes (TDEs) play a pivotal role in tumor establishment and progression, and are emerging biomarkers for tumor diagnosis in personalized medicine. To date, there is a lack of efficient technology platforms for exosome isolation and characterization. Multiple myeloma (MM) is an incurable B-cell malignancy due to the rapid development of drug-resistance. MM-released exosomes express the immunoglobulin B-cell receptor (Ig-BCR) of the tumor B-cells, which can be targeted by Idiotype-binding peptides (Id-peptides). In this study, we analyzed the production of MM-released exosomes in the murine 5T33MM multiple myeloma model as biomarkers of tumor growth. To this end, we selected Id-peptides by screening a phage display library using as bait the Ig-BCR expressed by 5T33MM cells. By FACS, the FITC-conjugated Id-peptides detected the MM-released exosomes in the serum of 5T33MM-engrafted mice, levels of which are correlated with tumor progression at an earlier time point compared to serum paraprotein. These results indicate that Id-peptide-based recognition of MM-released exosomes may represent a very sensitive diagnostic approach for clinical evaluation of disease progression.

Bioactive peptides released from Saccharomyces cerevisiae under accelerated autolysis in a wine model system.

Science.gov (United States)

Alcaide-Hidalgo, J M; Pueyo, E; Polo, M C; Martínez-Rodríguez, A J

2007-09-01

The ACE inhibitory activity (IACE) and the oxygen radical absorbance capacity (ORAC-FL) values of yeast peptides isolated from a model wine during accelerated autolysis of Saccharomyces cerevisiae have been studied. Samples were taken at 6, 24, 48, 121, and 144 h of autolysis. Peptide concentration increased throughout autolysis process. Peptides were fractionated into 2 fractions: F1, constituted by hydrophilic peptides, and F2, containing hydrophobic peptides. Both IACE activity and ORAC-FL values increased during 121 h of autolysis, then decreased afterward. Peptide fraction F2 was the main fraction involved in IACE activity and ORAC-FL.

Epinephrine in the heart: uptake and release, but no facilitation of norepinephrine release

NARCIS (Netherlands)

Th.W. Lameris (Thomas); P.A. de Zeeuw (Sandra); D.J.G.M. Duncker (Dirk); W. Tietge; G. Alberts; F. Boomsma (Frans); P.D. Verdouw (Pieter); A.H. van den Meiracker (Anton)

2002-01-01

textabstractBACKGROUND: Several studies have suggested that epinephrine augments the release of norepinephrine from sympathetic nerve terminals through stimulation of presynaptic receptors, but evidence pertaining to this mechanism in the heart is scarce and conflicting. Using

Electrical stimulation of the isolated rat intestine in the presence of nutrient stimulus enhances glucagon-like peptide-1 release

International Nuclear Information System (INIS)

Schwartz, Ann; Ort, Tatiana; Kajekar, Radhika; Hornby, Pamela J; Wade, Paul R

2010-01-01

The release of small intestinal hormones by constituents of ingested food, such as fatty acids, is integral to post-prandial responses that reduce food intake. Recent evidence suggests that small intestinal electrical stimulation reduces food intake, although the mechanism of action is debated. To test the hypothesis that intestinal stimulation directly alters hormone release locally we used isolated rat distal ileum and measured glucagon-like peptide-1 (GLP-1) released in the presence or absence of linoleic acid (LA) and electrical field stimulation (EFS). Intact segments were oriented longitudinally between bipolar stimulating electrodes in organ bath chambers containing modified Krebs–Ringers bicarbonate (KRB) buffer including protease inhibitors. Incubation in LA (3 mg ml −1 ) for 45 min increased GLP-1 concentration (21.9 ± 2.6 pM versus KRB buffer alone 3.6 ± 0.1 pM). Eleven electrical stimulation conditions were tested. In the presence of LA none of the stimulation conditions inhibited LA-evoked GLP-1 release, whereas two high frequency short pulse widths (14 V, 20 Hz, 5 ms and 14 V, 40 Hz, 5 ms) and one low frequency long pulse width (14 V, 0.4 Hz, 300 ms) EFS conditions enhanced LA-evoked GLP-1 release by >250%. These results are consistent with a local effect of intestinal electrical stimulation to enhance GLP-1 release in response to luminal nutrients in the intestines. Enhancing hormone release could improve the efficacy of intestinal electrical stimulation and provide a potential treatment for obesity and metabolic conditions

Synthetic Growth Hormone-Releasing Peptides (GHRPs: A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects

Directory of Open Access Journals (Sweden)

Jorge Berlanga-Acosta

2017-02-01

Full Text Available Background: Growth hormone-releasing peptides (GHRPs constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36, which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.

Effects of NSAIDs on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Trigeminal Ganglia

Directory of Open Access Journals (Sweden)

Vittorio Vellani

2017-01-01

Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are frequently used to treat migraine, but the mechanisms of their effects in this pathology are not fully elucidated. The trigeminal ganglia and calcitonin gene-related peptide (CGRP have been implicated in the pathophysiology of migraine. The release of CGRP and prostaglandin E2 (PGE2 from freshly isolated rat trigeminal ganglia was evaluated after oral administration of nimesulide, etoricoxib, and ketoprofen, NSAIDs with different pharmacological features. Thirty minutes after oral administration, nimesulide, 10 mg/Kg, decreased the GCRP release induced by an inflammatory soup, while the other NSAIDs were ineffective at this point in time. Two hours after oral nimesulide (5 and 10 mg/Kg and ketoprofen (10 mg/Kg, but not of etoricoxib, a significant decrease in the CGRP release was observed. All drugs reduced PGE2, although with some differences in timing and doses, and the action on CGRP does not seem to be related to PGE2 inhibition. The reduction of CGRP release from rat trigeminal ganglia after nimesulide and ketoprofen may help to explain the mechanism of action of NSAIDs in migraine. Since at 30 minutes only nimesulide was effective in reducing CGRP release, these results suggest that this NSAID may exert a particularly rapid effect in patients with migraine.

Delta-sleep inducing peptide entrapment in the charged macroporous matrices

International Nuclear Information System (INIS)

Sukhanova, Tatiana V.; Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A.; Prudchenko, Igor A.; Shtilman, Mikhail I.; Markvicheva, Elena A.

2014-01-01

Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable

Delta-sleep inducing peptide entrapment in the charged macroporous matrices

Energy Technology Data Exchange (ETDEWEB)

Sukhanova, Tatiana V., E-mail: sukhanovat@mail.ru [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Cell Interactions, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Prudchenko, Igor A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Peptide Chemistry, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Shtilman, Mikhail I. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Markvicheva, Elena A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory Polymers for Biology, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation)

2014-09-01

Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable.

Expression of the Gastrin-Releasing Peptide Receptor, the Prostate Stem Cell Antigen and the Prostate-Specific Membrane Antigen in Lymph Node and Bone Metastases of Prostate Cancer

NARCIS (Netherlands)

Ananias, Hildo J. K.; van den Heuvel, Marius C.; Helfrich, Wijnand; de Jong, Igle J.

2009-01-01

OBJECTIVE. Cell membrane antigens like the gastrin-releasing peptide receptor (GRPR), the prostate stem cell antigen (PSCA), and the prostate-specific membrane antigen (PSMA), expressed in prostate cancer, are attractive targets for new therapeutic and diagnostic applications. Therefore, we

Enhancement of anti-tumor activity of hybrid peptide in conjugation with carboxymethyl dextran via disulfide linkers.

Science.gov (United States)

Gaowa, Arong; Horibe, Tomohisa; Kohno, Masayuki; Tabata, Yasuhiko; Harada, Hiroshi; Hiraoka, Masahiro; Kawakami, Koji

2015-05-01

To improve the anti-tumor activity of EGFR2R-lytic hybrid peptide, we prepared peptide-modified dextran conjugates with the disulfide bonds between thiolated carboxymethyl dextran (CMD-Cys) and cysteine-conjugated peptide (EGFR2R-lytic-Cys). In vitro release studies showed that the peptide was released from the CMD-s-s-peptide conjugate in a concentration-dependent manner in the presence of glutathione (GSH, 2μM-2mM). The CMD-s-s-peptide conjugate exhibited a similar cytotoxic activity with free peptide alone against human pancreatic cancer BxPC-3 cells in vitro. Furthermore, it was shown that the CMD-s-s-peptide conjugates were highly accumulated in tumor tissue in a mouse xenograft model using BxPC-3 cells, and the anti-tumor activity of the conjugate was more effective than that of the free peptide. In addition, the plasma concentrations of peptide were moderately increased and the elimination half-life of the peptide was prolonged after intravenous injection of CMD-s-s-peptide conjugates. These results demonstrated that the conjugate based on thiolated CMD polymer would be potentially useful carriers for the sustained release of the hybrid peptide in vivo. Copyright © 2015 Elsevier B.V. All rights reserved.

Mobile Collaborative Augmented Reality: The Augmented Stroll

OpenAIRE

Renevier , Philippe; Nigay , Laurence

2001-01-01

International audience; The paper focuses on Augmented Reality systems in which interaction with the real world is augmented by the computer, the task being performed in the real world. We first define what mobile AR systems, collaborative AR systems and finally mobile and collaborative AR systems are. We then present the augmented stroll and its software design as one example of a mobile and collaborative AR system. The augmented stroll is applied to Archaeology in the MAGIC (Mobile Augmente...

Intracellular Signalling by C-Peptide

Directory of Open Access Journals (Sweden)

Claire E. Hills

2008-01-01

Full Text Available C-peptide, a cleavage product of the proinsulin molecule, has long been regarded as biologically inert, serving merely as a surrogate marker for insulin release. Recent findings demonstrate both a physiological and protective role of C-peptide when administered to individuals with type I diabetes. Data indicate that C-peptide appears to bind in nanomolar concentrations to a cell surface receptor which is most likely to be G-protein coupled. Binding of C-peptide initiates multiple cellular effects, evoking a rise in intracellular calcium, increased PI-3-kinase activity, stimulation of the Na+/K+ ATPase, increased eNOS transcription, and activation of the MAPK signalling pathway. These cell signalling effects have been studied in multiple cell types from multiple tissues. Overall these observations raise the possibility that C-peptide may serve as a potential therapeutic agent for the treatment or prevention of long-term complications associated with diabetes.

Peptide-Loaded Solid Lipid Nanoparticles Prepared through Coacervation Technique

Directory of Open Access Journals (Sweden)

Marina Gallarate

2011-01-01

Full Text Available Stearic acid solid lipid nanoparticles were prepared according to a new technique, called coacervation. The main goal of this experimental work was the entrapment of peptide drugs into SLN, which is a difficult task, since their chemical characteristics (molecular weight, hydrophilicity, and stability hamper peptide-containing formulations. Insulin and leuprolide, chosen as model peptide drugs, were encapsulated within nanoparticles after hydrophobic ion pairing with anionic surfactants. Peptide integrity was maintained after encapsulation, and nanoparticles can act in vitro as a sustained release system for peptide.

The effect of tartrazine on histamine release from rat peritoneal mast cells.

Science.gov (United States)

Safford, R J; Goodwin, B F

1984-01-01

The release of histamine from purified rat peritoneal mast cells induced by specific antigen (egg albumin), compound 48/80 and calcium ionophore A23187 was modified by tartrazine. Histamine release induced by 48/80 and antigen was inhibited by the presence of 10(-5) to 10(-2)M tartrazine. The inhibitory effect on egg albumin induced histamine release was maximal when the tartrazine was added simultaneously with egg albumin, and was reduced by increased preincubation of the cells with tartrazine. Tartrazine had a small inhibitory effect on ionophore induced release at high concentrations, but augmented histamine release at tartrazine concentrations of 10(-3) and 10(-4)M. Augmentation of ionophore induced release was maximal at between 0-5 min preincubation of the cells with tartrazine.

Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

DEFF Research Database (Denmark)

Bork, E; Hansen, M; Urdal, P

1988-01-01

Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

Effects of short-term glucocorticoid deprivation on growth hormone (GH) response to GH-releasing peptide-6: Studies in normal men and in patients with adrenal insufficiency

OpenAIRE

Pinto, Ana Claudia de Assis Rocha [UNIFESP; Dias-da-Silva, Magnus Régios [UNIFESP; Martins, Manoel R. [UNIFESP; Brunner, Elisa [UNIFESP; Lengyel, Ana Maria Judith [UNIFESP

2000-01-01

There are no data in the literature about the effects of glucocorticoid deprivation on GH-releasing peptide-g (GHRP-6)-induced GH release. the aims of this study were to evaluate GH responsiveness to GHRP-6 1) after metyrapone administration in normal men, and 2) in patients with chronic hypocortisolism after glucocorticoid withdrawal for 72 h. in normal subjects, metyrapone ingestion did not alter significantly GH responsiveness to GHRP-6 [n = 8; peak, 39.3 +/- 7.1 mu g/L; area under the cur...

Bioreducible Fluorinated Peptide Dendrimers Capable of Circumventing Various Physiological Barriers for Highly Efficient and Safe Gene Delivery.

Science.gov (United States)

Cai, Xiaojun; Jin, Rongrong; Wang, Jiali; Yue, Dong; Jiang, Qian; Wu, Yao; Gu, Zhongwei

2016-03-09

Polymeric vectors have shown great promise in the development of safe and efficient gene delivery systems; however, only a few have been developed in clinical settings due to poor transport across multiple physiological barriers. To address this issue and promote clinical translocation of polymeric vectors, a new type of polymeric vector, bioreducible fluorinated peptide dendrimers (BFPDs), was designed and synthesized by reversible cross-linking of fluorinated low generation peptide dendrimers. Through masterly integration all of the features of reversible cross-linking, fluorination, and polyhedral oligomeric silsesquioxane (POSS) core-based peptide dendrimers, this novel vector exhibited lots of unique features, including (i) inactive surface to resist protein interactions; (ii) virus-mimicking surface topography to augment cellular uptake; (iii) fluorination-mediated efficient cellular uptake, endosome escape, cytoplasm trafficking, and nuclear entry, and (iv) disulfide-cleavage-mediated polyplex disassembly and DNA release that allows efficient DNA transcription. Noteworthy, all of these features are functionally important and can synergistically facilitate DNA transport from solution to the nucleus. As a consequences, BFPDs showed excellent gene transfection efficiency in several cell lines (∼95% in HEK293 cells) and superior biocompatibility compared with polyethylenimine (PEI). Meanwhile BFPDs provided excellent serum resistance in gene delivery. More importantly, BFPDs offer considerable in vivo gene transfection efficiency (in muscular tissues and in HepG2 tumor xenografts), which was approximately 77-fold higher than that of PEI in luciferase activity. These results suggest bioreducible fluorinated peptide dendrimers are a new class of highly efficient and safe gene delivery vectors and should be used in clinical settings.

Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

OpenAIRE

Bell, Andrew M; Gutierrez-Mecinas, Maria; Polg?r, Erika; Todd, Andrew J

2016-01-01

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphoryla...

Solid-phase peptide quantitation assay using labeled monoclonal antibody and glutaraldehyde fixation

International Nuclear Information System (INIS)

Kasprzyk, P.G.; Cuttitta, F.; Avis, I.; Nakanishi, Y.; Treston, A.; Wong, H.; Walsh, J.H.; Mulshine, J.L.

1988-01-01

A solid-phase radioimmunoassay utilizing iodinated peptide-specific monoclonal antibody as a detection system instead of labeled peptide has been developed. Regional specific monoclonal antibodies to either gastrin-releasing peptide or gastrin were used as models to validate the general application of our modified assay. Conditions for radioactive labeling of the monoclonal antibody were determined to minimize oxidant damage, which compromises the sensitivity of other reported peptide quantitation assays. Pretreatment of 96-well polyvinyl chloride test plates with a 5% glutaraldehyde solution resulted in consistent retention of sufficient target peptide on the solid-phase matrix to allow precise quantitation. This quantitative method is completed within 1 h of peptide solid phasing. Pretreatment of assay plates with glutaraldehyde increased binding of target peptide and maximized antibody binding by optimizing antigen presentation. The hypothesis that glutaraldehyde affects both peptide binding to the plate and orientation of the peptide was confirmed by analysis of several peptide analogs. These studies indicate that peptide binding was mediated through a free amino group leaving the carboxy-terminal portion of the target peptide accessible for antibody binding. It was observed that the length of the peptide also affects the amount of monoclonal antibody that will bind. Under the optimal conditions, results from quantitation of gastrin-releasing peptide in relevant samples agree well with those from previously reported techniques. Thus, we report here a modified microplate assay which may be generally applied for the rapid and sensitive quantitation of peptide hormones

Pre-clinical evaluation of eight DOTA coupled gastrin-releasing peptide receptor (GRP-R) ligands for in vivo targeting of receptor-expressing tumors.

Science.gov (United States)

Accardo, Antonella; Galli, Filippo; Mansi, Rosalba; Del Pozzo, Luigi; Aurilio, Michela; Morisco, Anna; Ringhieri, Paola; Signore, Alberto; Morelli, Giancarlo; Aloj, Luigi

2016-12-01

Overexpression of the gastrin-releasing peptide receptor (GRP-R) has been documented in several human neoplasms such as breast, prostate, and ovarian cancer. There is growing interest in developing radiolabeled peptide-based ligands toward these receptors for the purpose of in vivo imaging and radionuclide therapy of GRP-R-overexpressing tumors. A number of different peptide sequences, isotopes, and labeling methods have been proposed for this purpose. The aim of this work is to perform a direct side-by-side comparison of different GRP-R binding peptides utilizing a single labeling strategy to identify the most suitable peptide sequence. Solid-phase synthesis of eight derivatives (BN1-8) designed based on literature analysis was carried out. Peptides were coupled to the DOTA chelator through a PEG4 spacer at the N-terminus. Derivatives were characterized for serum stability, binding affinity on PC-3 human prostate cancer cells, biodistribution in tumor-bearing mice, and gamma camera imaging at 1, 6, and 24 h after injection. Serum stability was quite variable among the different compounds with half-lives ranging from 16 to 400 min at 37 °C. All compounds tested showed K d values in the nanomolar range with the exception of BN3 that showed no binding. Biodistribution and imaging studies carried out for compounds BN1, BN4, BN7, and BN8 showed targeting of the GRP-R-positive tumors and the pancreas. The BN8 compound (DOTA-PEG-DPhe-Gln-Trp-Ala-Val-NMeGly-His-Sta-Leu-NH2) showed high affinity, the longest serum stability, and the highest target-to-background ratios in biodistribution and imaging experiments among the compounds tested. Our results indicate that the NMeGly for Gly substitution and the Sta-Leu substitution at the C-terminus confer high serum stability while maintaining high receptor affinity, resulting in biodistribution properties that outperform those of the other peptides.

Anorexia induction by the trichothecene deoxynivalenol (vomitoxin) is mediated by the release of the gut satiety hormone peptide YY.

Science.gov (United States)

Flannery, Brenna M; Clark, Erica S; Pestka, James J

2012-12-01

Consumption of deoxynivalenol (DON), a trichothecene mycotoxin known to commonly contaminate grain-based foods, suppresses growth of experimental animals, thus raising concerns over its potential to adversely affect young children. Although this growth impairment is believed to result from anorexia, the initiating mechanisms for appetite suppression remain unknown. Here, we tested the hypothesis that DON induces the release of satiety hormones and that this response corresponds to the toxin's anorectic action. Acute ip exposure to DON had no effect on plasma glucagon-like peptide-1, leptin, amylin, pancreatic polypeptide, gastric inhibitory peptide, or ghrelin; however, the toxin was found to robustly elevate peptide YY (PYY) and cholecystokinin (CCK). Specifically, ip exposure to DON at 1 and 5mg/kg bw induced PYY by up to 2.5-fold and CCK by up to 4.1-fold. These responses peaked within 15-120 min and lasted up to 120 min (CCK) and 240 min (PPY), corresponding with depressed rates of food intake. Direct administration of exogenous PYY or CCK similarly caused reduced food intake. Food intake experiments using the NPY2 receptor antagonist BIIE0246 and the CCK1A receptor antagonist devazepide, individually, suggested that PYY mediated DON-induced anorexia but CCK did not. Orolingual exposure to DON induced plasma PYY and CCK elevation and anorexia comparable with that observed for ip exposure. Taken together, these findings suggest that PYY might be one critical mediator of DON-induced anorexia and, ultimately, growth suppression.

Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Pankratova, Stanislava; Nielsen, Peter E

2005-01-01

Cell-penetrating peptides have been widely used to improve cellular delivery of a variety of proteins and antisense agents. However, recent studies indicate that such cationic peptides are predominantly entering cells via an endosomal pathway. We now show that the nuclear antisense effect in He......La cells of a variety of peptide nucleic acid (PNA) peptide conjugates is significantly enhanced by addition of 6 mM Ca(2+) (as well as by the lysosomotrophic agent chloroquine). In particular, the antisense activities of Tat(48-60) and heptaarginine-conjugated PNAs were increased 44-fold and 8.5-fold......, respectively. Evidence is presented that the mechanism involves endosomal release. The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route...

Cardioprotective peptides from marine sources.

Science.gov (United States)

Harnedy, Padraigín A; FitzGerald, Richard J

2013-05-01

Elevated blood pressure or hypertension is one of the fastest growing health problems worldwide. Although the etiology of essential hypertension has a genetic component, dietary factors play an important role. With the high costs and adverse side-effects associated with synthetic antihypertensive drugs and the awareness of the link between diet and health there has been increased focus on identification of food components that may contribute to cardiovascular health. In recent years special interest has been paid to the cardioprotective activity of peptides derived from food proteins including marine proteins. These peptides are latent within the sequence of the parent protein and only become active when released by proteolytic digestion during gastrointestinal digestion or through food processing. Current data on antihypertensive activity of marine-derived protein hydrolysates/peptides in animal and human studies is reviewed herein. Furthermore, products containing protein hydrolysates/peptides from marine origin with antihypertensive effects are discussed.

Effects of irradiation on the circadian rhythm in the release of peptides in the suprachiasmatic nucleus culture

Energy Technology Data Exchange (ETDEWEB)

Saito, Kimihiko [Yokohama City Univ. (Japan). School of Medicine

2000-03-01

Mammalian circadian rhythms are regulated by the circadian clock which is located in the hypothalamic suprachiasmatic nucleus (SCN). In the present study, we examined the effect of irradiation on the circadian rhythm in the release of arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in slice cultures of the rat SCN. The effect of irradiation on the glial cell proliferation in the SCN culture was also examined by the immunohistochemical method. In SCN cultures which received irradiation, circadian rhythms in the release of AVP and VIP were detected, as observed in the SCN culture not irradiated. However, the AVP and VIP rhythms showed various phase angle differences in some cultures irradiated, which suggested that irradiation caused a looseness of coupling between AVP and VIP oscillators. On the other hand, the number of glial cells was decreased by irradiation. These results suggested that the dissociation of the two peptide rhythms after irradiation might be due to the inhibition of glial cell proliferation. Furthermore, the radiation changed the amplitude of AVP and VIP rhythms, suggesting that couplings within both AVP and VIP oscillators were influenced by irradiation. (author)

Effects of irradiation on the circadian rhythm in the release of peptides in the suprachiasmatic nucleus culture

International Nuclear Information System (INIS)

Saito, Kimihiko

2000-01-01

Mammalian circadian rhythms are regulated by the circadian clock which is located in the hypothalamic suprachiasmatic nucleus (SCN). In the present study, we examined the effect of irradiation on the circadian rhythm in the release of arginine-vasopressin (AVP) and vasoactive intestinal polypeptide (VIP) in slice cultures of the rat SCN. The effect of irradiation on the glial cell proliferation in the SCN culture was also examined by the immunohistochemical method. In SCN cultures which received irradiation, circadian rhythms in the release of AVP and VIP were detected, as observed in the SCN culture not irradiated. However, the AVP and VIP rhythms showed various phase angle differences in some cultures irradiated, which suggested that irradiation caused a looseness of coupling between AVP and VIP oscillators. On the other hand, the number of glial cells was decreased by irradiation. These results suggested that the dissociation of the two peptide rhythms after irradiation might be due to the inhibition of glial cell proliferation. Furthermore, the radiation changed the amplitude of AVP and VIP rhythms, suggesting that couplings within both AVP and VIP oscillators were influenced by irradiation. (author)

Steviol Glycoside Rebaudioside A Induces Glucagon-like Peptide-1 and Peptide YY Release in a Porcine ex Vivo Intestinal Model

NARCIS (Netherlands)

Ripken, D.; Wielen, N. van der; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.J.

2014-01-01

Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called “ileal brake”. The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue

Steviol glycoside rebaudioside A induces glucagon-like peptide-1 and peptide YY release in a porcine ex vivo intestinal model

NARCIS (Netherlands)

Ripken, D.; Wielen, van der N.; Wortelboer, H.M.; Meijerink, J.; Witkamp, R.F.; Hendriks, H.F.

2014-01-01

Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are hormones important for satiation and are involved in the process called "ileal brake". The aim of this study was to investigate the GLP-1- and PYY-stimulating efficacy of rebaudioside A, casein, and sucrose. This was studied using tissue

Determination of antioxidant activity of bioactive peptide fractions obtained from yogurt.

Science.gov (United States)

Aloğlu, H Sanlıdere; Oner, Z

2011-11-01

In this study, physicochemical and microbiological properties of traditional and commercial yogurt samples were determined during 4 wk of storage. Proteolytic activity, which occurs during the storage period of yogurt samples, was also determined. Peptide fractions obtained from yogurts were investigated and the effect of proteolysis on peptide release during storage was determined. The antioxidant activities of peptides released from yogurt water-soluble extracts (WSE) and from HPLC fractions were determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) methods. The antioxidant activity of WSE from traditional yogurt was greater than that of WSE from commercial yogurts. In analysis by the ABTS method, mean values increased from 7.697 to 8.739 mM Trolox/g in commercial yogurts, and from 10.115 to 13.182 mM Trolox/g in traditional yogurts during storage. Antioxidant activities of peptides released from HPLC fractions of selected yogurt samples increased 10 to 200 times. In all yogurt samples, the greatest antioxidant activity was shown in the F2 fraction. After further fractionation of yogurt samples, the fractions coded as F2.2, F2.3, F4.3, and F4.4 had the highest antioxidant activity values. Total antioxidant activity of yogurts was low but after purification of peptides by fractionation in HPLC, peptide fractions with high antioxidant activity were obtained. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Structure determination by 1H NMR spectroscopy of (sulfated) sialylated N-linked carbohydrate chains released from porcine thyroglobulin by peptide-N4-(N-acetyl-β-glucosaminyl)asparagine amidase-F

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Waard, P. de; Koorevaar, A.; Kamerling, J.P.

1991-01-01

The N-linked carbohydrate chains of porcine thyroglobulin were released by peptide-N4-(N-acetyl-β-glucosaminyl)asparagine amidase-F (PNGase- F). The resulting oligosaccharides were fractionated by a combination of fast protein liquid chromatography and high performance liquid chromatography and

Meat and fermented meat products as a source of bioactive peptides.

Science.gov (United States)

Stadnik, Joanna; Kęska, Paulina

2015-01-01

Bioactive peptides are short amino acid sequences, that upon release from the parent protein may play different physiological roles, including antioxidant, antihypertensive, antimicrobial, and other bioactivities. They have been identified from a range of foods, including those of animal origin, e.g., milk and muscle sources (with pork, beef, or chicken and various species of fish and marine organism). Bioactive peptides are encrypted within the sequence of the parent protein molecule and latent until released and activated by enzymatic proteolysis, e.g. during gastrointestinal digestion or food processing. Bioactive peptides derived from food sources have the potential for incorporation into functional foods and nutraceuticals. The aim of this paper is to present an overview of the muscle-derived bioactive peptides, especially those of fermented meats and the potential benefits of these bioactive compounds to human health.

Transformable Peptide Nanocarriers for Expeditious Drug Release and Effective Cancer Therapy via Cancer-Associated Fibroblast Activation.

Science.gov (United States)

Ji, Tianjiao; Zhao, Ying; Ding, Yanping; Wang, Jing; Zhao, Ruifang; Lang, Jiayan; Qin, Hao; Liu, Xiaoman; Shi, Jian; Tao, Ning; Qin, Zhihai; Nie, Guangjun; Zhao, Yuliang

2016-01-18

A novel cleavable amphiphilic peptide (CAP) was designed to be specifically responsive to fibroblast activation protein-α (FAP-α), a protease specifically expressed on the surface of cancer-associated fibroblasts. The CAP self-assembled into fiber-like nanostructures in solution, while the presence of hydrophobic chemotherapeutic drugs readily transformed the assemblies into drug-loaded spherical nanoparticles. The disassembly of these nanoparticles (CAP-NPs) upon FAP-α cleavage resulted in rapid and efficient release of the encapsulated drugs specifically at tumor sites. This Transformers-like drug delivery strategy could allow them to disrupt the stromal barrier and enhance local drug accumulation. Therapeutic results suggested that drug-loaded CAP-NPs hold promising tumor specificity and therapeutic efficacy for various solid tumor models, confirming its potential utility and versatility in antitumor therapy. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Towards Pervasive Augmented Reality: Context-Awareness in Augmented Reality.

Science.gov (United States)

Grubert, Jens; Langlotz, Tobias; Zollmann, Stefanie; Regenbrecht, Holger

2017-06-01

Augmented Reality is a technique that enables users to interact with their physical environment through the overlay of digital information. While being researched for decades, more recently, Augmented Reality moved out of the research labs and into the field. While most of the applications are used sporadically and for one particular task only, current and future scenarios will provide a continuous and multi-purpose user experience. Therefore, in this paper, we present the concept of Pervasive Augmented Reality, aiming to provide such an experience by sensing the user's current context and adapting the AR system based on the changing requirements and constraints. We present a taxonomy for Pervasive Augmented Reality and context-aware Augmented Reality, which classifies context sources and context targets relevant for implementing such a context-aware, continuous Augmented Reality experience. We further summarize existing approaches that contribute towards Pervasive Augmented Reality. Based our taxonomy and survey, we identify challenges for future research directions in Pervasive Augmented Reality.

Lack of effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids on intestinal peptide release and adipokines in healthy female subjects

Directory of Open Access Journals (Sweden)

Ingunn Naverud

2016-08-01

Full Text Available Peptides released from the small intestine and colon regulate short-term food intake by suppressing appetite and inducing satiety. Intake of marine omega-3 (n-3 fatty acids from fish and fish oils is associated with beneficial health effects, whereas the relation between intake of the vegetable n-3 fatty acid α-linolenic acid and diseases is less clear. The aim of the present study was to investigate the postprandial effects of a single high-fat meal enriched with vegetable n-3 or a combination of vegetable and marine n-3 fatty acids with their different unsaturated fatty acid composition on intestinal peptide release and the adipose tissue. Fourteen healthy lean females consumed three test meals with different fat quality in a fixed order. The test meal consisted of three cakes enriched with coconut fat, linseed oil and a combination of linseed and cod liver oil. The test days were separated by two weeks. Fasting and postprandial blood samples at three and six hours after intake were analysed. A significant postprandial effect was observed for cholecystokinin, peptide YY, glucose-dependent insulinotropic polypeptide, amylin and insulin which increased, while leptin decreased postprandially independent of the fat composition in the high-fat meal. In conclusion, in healthy, young, lean females, an intake of a high-fat meal enriched with n-3 fatty acids from different origin stimulates intestinal peptide release without any difference between the different fat compositions.

New Gastrin Releasing Peptide Receptor-Directed [99mTc]Demobesin 1 Mimics: Synthesis and Comparative Evaluation.

Science.gov (United States)

Nock, Berthold A; Charalambidis, David; Sallegger, Werner; Waser, Beatrice; Mansi, Rosalba; Nicolas, Guillaume P; Ketani, Eleni; Nikolopoulou, Anastasia; Fani, Melpomeni; Reubi, Jean-Claude; Maina, Theodosia

2018-04-12

We have previously reported on the gastrin releasing peptide receptor (GRPR) antagonist [ 99m Tc]1, ([ 99m Tc]demobesin 1, 99m Tc-[N 4 '-diglycolate-dPhe 6 ,Leu-NHEt 13 ]BBN(6-13)). [ 99m Tc]1 has shown superior biological profile compared to analogous agonist-based 99m Tc-radioligands. We herein present a small library of [ 99m Tc]1 mimics generated after structural modifications in (a) the linker ([ 99m Tc]2, [ 99m Tc]3, [ 99m Tc]4), (b) the peptide chain ([ 99m Tc]5, [ 99m Tc]6), and (c) the C-terminus ([ 99m Tc]7 or [ 99m Tc]8). The effects of above modifications on the biological properties of analogs were studied in PC-3 cells and tumor-bearing SCID mice. All analogs showed subnanomolar affinity for the human GRPR, while most receptor-affine 4 and 8 behaved as potent GRPR antagonists in a functional internalization assay. In mice bearing PC-3 tumors, [ 99m Tc]1-[ 99m Tc]6 exhibited GRPR-specific tumor uptake, rapidly clearing from normal tissues. [ 99m Tc]4 displayed the highest tumor uptake (28.8 ± 4.1%ID/g at 1 h pi), which remained high even after 24 h pi (16.3 ± 1.8%ID/g), well surpassing that of [ 99m Tc]1 (5.4 ± 0.7%ID/g at 24 h pi).

Extraction of aggrecan-peptide from cartilage by tissue autolysis.

Science.gov (United States)

Nakano, Takuo; Srichamroen, Anchalee; Ozimek, Lech

2014-01-01

Aggrecan is a cartilage specific proteoglycan containing chondroitin sulfate (CS) and keratan sulfate (KS). CS is an acidic polysaccharide having wide range of applications in pharmaceutical, cosmetic, and food industries. CS is extracted from cartilage by tissue proteolysis with an exogenous proteinase or by activating endogenous proteinases (autolysis) to release aggrecan-peptides from the tissue. This review is focused on the latter technique. Bovine nasal and tracheal cartilages, and broiler chicken sternum cartilage have been used for autolysis studies. To extract aggrecan-peptide, cartilage tissues are cut into small pieces, and incubated in a monovalent or divalent salt solution (e.g., 0.1 M sodium or calcium acetate) at pH 4.5 and 37 °C for 7 - 24 h. Most (~80% or more) of total tissue uronic acid, a constituent sugar of aggrecan, is extracted and released into the salt solution during incubation. Reextraction of the tissue residue results in release of a small amount of uronic acid. Aggrecan-peptides purified using anion exchange chromatography are large compounds containing CS and KS. On gel chromatography, they are excluded from the column of Sephacryl S-300. Chemical composition analysis demonstrated that aggrecan-peptides from either bovine or chicken cartilage contain >90% CS with small amount (autolysis has been used as a plate coating antigen in enzyme- linked immunosorbent assay (ELISA) to determine KS.

Influence of structural and surface properties of whey-derived peptides on zinc-chelating capacity, and in vitro gastric stability and bioaccessibility of the zinc-peptide complexes.

Science.gov (United States)

Udechukwu, M Chinonye; Downey, Brianna; Udenigwe, Chibuike C

2018-02-01

Gastrointestinal stability of zinc-peptide complexes is essential for zinc delivery. As peptide surface charge can influence their metal complex stability, we evaluated the zinc-chelating capacity and stability of zinc complexes of whey protein hydrolysates (WPH), produced with Everlase (WPH-Ever; ζ-potential, -39mV) and papain (WPH-Pap; ζ-potential, -7mV), during simulated digestion. WPH-Ever had lower amount of zinc-binding amino acids but showed higher zinc-chelating capacity than WPH-Pap. This is attributable to the highly anionic surface charge of WPH-Ever for electrostatic interaction with zinc. Release of zinc during peptic digestion was lower for WPH-Ever-zinc, and over 50% of zinc remained bound in both peptide complexes after peptic-pancreatic digestion. Fourier transform infrared spectroscopy suggests the involvement of carboxylate ion, and sidechain carbon-oxygen of aspartate/glutamate and serine/threonine in zinc-peptide complexation. The findings indicate that strong zinc chelation can promote gastric stability and impede intestinal release, for peptides intended for use as dietary zinc carriers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Exploring the role of peptides in polymer-based gene delivery.

Science.gov (United States)

Sun, Yanping; Yang, Zhen; Wang, Chunxi; Yang, Tianzhi; Cai, Cuifang; Zhao, Xiaoyun; Yang, Li; Ding, Pingtian

2017-09-15

Polymers are widely studied as non-viral gene vectors because of their strong DNA binding ability, capacity to carry large payload, flexibility of chemical modifications, low immunogenicity, and facile processes for manufacturing. However, high cytotoxicity and low transfection efficiency substantially restrict their application in clinical trials. Incorporating functional peptides is a promising approach to address these issues. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we systematically summarize the role of peptides in polymer-based gene delivery, and elaborate how to rationally design polymer-peptide based gene delivery vectors. Polymers are widely studied as non-viral gene vectors, but suffer from high cytotoxicity and low transfection efficiency. Incorporating short, bioactive peptides into polymer-based gene delivery systems can address this issue. Peptides demonstrate various functions in polymer-based gene delivery systems, such as targeting to specific cells, breaching membrane barriers, facilitating DNA condensation and release, and lowering cytotoxicity. In this review, we highlight the peptides' roles in polymer-based gene delivery, and elaborate how to utilize various functional peptides to enhance the transfection efficiency of polymers. The optimized peptide-polymer vectors should be able to alter their structures and functions according to biological microenvironments and utilize inherent intracellular pathways of cells, and consequently overcome the barriers during gene delivery to enhance transfection efficiency. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

Science.gov (United States)

Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

2018-01-01

The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

Delivery systems for antimicrobial peptides

DEFF Research Database (Denmark)

Nordström, Randi; Malmsten, Martin

2017-01-01

Due to rapidly increasing resistance development against conventional antibiotics, finding novel approaches for the treatment of infections has emerged as a key health issue. Antimicrobial peptides (AMPs) have attracted interest in this context, and there is by now a considerable literature...... on the identification such peptides, as well as on their optimization to reach potent antimicrobial and anti-inflammatory effects at simultaneously low toxicity against human cells. In comparison, delivery systems for antimicrobial peptides have attracted considerably less interest. However, such delivery systems...... are likely to play a key role in the development of potent and safe AMP-based therapeutics, e.g., through reducing chemical or biological degradation of AMPs either in the formulation or after administration, by reducing adverse side-effects, by controlling AMP release rate, by promoting biofilm penetration...

ARLearn: augmented reality meets augmented virtuality

NARCIS (Netherlands)

Ternier, Stefaan; Klemke, Roland; Kalz, Marco; Van Ulzen, Patricia; Specht, Marcus

2012-01-01

Ternier, S., Klemke, R., Kalz, M., Van Ulzen, P., & Specht, M. (2012). ARLearn: augmented reality meets augmented virtuality [Special issue]. Journal of Universal Computer Science - Technology for learning across physical and virtual spaces, 18(15), 2143-2164.

The gastric acid secretagogue gastrin-releasing peptide and the inhibitor oxyntomodulin do not exert their effect directly on the parietal cell in the rat

DEFF Research Database (Denmark)

Poulsen, Steen Seier; Holst, J J

1988-01-01

in vitro by measuring [14C]-aminopyrine accumulation, a reliable index of H+ generation, in isolated rat parietal cells. However, neither gastrin-releasing peptide nor oxyntomodulin influenced basal acid secretion or histamine-stimulated gastric acid secretion. Electron-microscopic studies of unstimulated...... and histamine-stimulated parietal cells confirmed that the cells retained the normal morphology of intracellular organelles and that the cells responded to physiological stimulation by marked expansion of the intracellular canaliculi....

Transforming Polar Research with Google Glass Augmented Reality (Invited)

Science.gov (United States)

Ruthkoski, T.

2013-12-01

Augmented reality is a new technology with the potential to accelerate the advancement of science, particularly in geophysical research. Augmented reality is defined as a live, direct or indirect, view of a physical, real-world environment whose elements are augmented (or supplemented) by computer-generated sensory input such as sound, video, graphics or GPS data. When paired with advanced computing techniques on cloud resources, augmented reality has the potential to improve data collection techniques, visualizations, as well as in-situ analysis for many areas of research. Google is currently a pioneer of augmented reality technology and has released beta versions of their wearable computing device, Google Glass, to a select number of developers and beta testers. This community of 'Glass Explorers' is the vehicle from which Google shapes the future of their augmented reality device. Example applications of Google Glass in geophysical research range from use as a data gathering interface in harsh climates to an on-site visualization and analysis tool. Early participation in the shaping of the Google Glass device is an opportunity for researchers to tailor this new technology to their specific needs. The purpose of this presentation is to provide geophysical researchers with a hands-on first look at Google Glass and its potential as a scientific tool. Attendees will be given an overview of the technical specifications as well as a live demonstration of the device. Potential applications to geophysical research in polar regions will be the primary focus. The presentation will conclude with an open call to participate, during which attendees may indicate interest in developing projects that integrate Google Glass into their research. Application Mockup: Penguin Counter Google Glass Augmented Reality Device

Central ventilatory and cardiovascular actions of trout gastrin-releasing peptide (GRP in the unanesthetized trout

Directory of Open Access Journals (Sweden)

Jean-Claude Le Mével

2013-07-01

Gastrin-releasing peptide (GRP, a neuropeptide initially isolated from porcine stomach, shares sequence similarity with bombesin. GRP and its receptors are present in the brains and peripheral tissues of several species of teleost fish, but little is known about the ventilatory and cardiovascular effects of this peptide in these vertebrates. The goal of this study was to compare the central and peripheral actions of picomolar doses of trout GRP on ventilatory and cardiovascular variables in the unanesthetized rainbow trout. Compared to vehicle, intracerebroventricular (ICV injection of GRP (1–50 pmol significantly elevated the ventilation rate (ƒV and the ventilation amplitude (VAMP, and consequently the total ventilation (VTOT. The maximum hyperventilatory effect of GRP (VTOT: +225%, observed at a dose of 50 pmol, was mostly due to its stimulatory action on VAMP (+170% rather than ƒV (+20%. In addition, ICV GRP (50 pmol produced a significant increase in mean dorsal aortic blood pressure (PDA (+35% and in heart rate (ƒH (+25%. Intra-arterial injections of GRP (5–100 pmol were without sustained effect on the ventilatory variables but produced sporadic and transient increases in ventilatory movement at doses of 50 and 100 pmol. At these doses, GRP elevated PDA by +20% but only the 50 pmol dose significantly increased HR (+15%. In conclusion, our study suggests that endogenous GRP within the brain of the trout may act as a potent neurotransmitter and/or neuromodulator in the regulation of cardio-ventilatory functions. In the periphery, endogenous GRP may act as locally-acting and/or circulating neurohormone with an involvement in vasoregulatory mechanisms.

Release kinetics of N-terminal pro-B-type natriuretic peptide in a clinical model of acute myocardial infarction.

Science.gov (United States)

Liebetrau, Christoph; Gaede, Luise; Dörr, Oliver; Troidl, Christian; Voss, Sandra; Hoffmann, Jedrzej; Paszko, Agata; Weber, Michael; Rolf, Andreas; Hamm, Christian; Nef, Holger; Möllmann, Helge

2014-02-15

N-terminal segment of B-type natriuretic peptide prohormone (NT-proBNP) is elevated in patients with acute myocardial infarction (AMI) thus providing both diagnostic information and prognostic information. The aim of the present study was to determine the time course of NT-proBNP release in patients undergoing transcoronary ablation of septal hypertrophy (TASH) a procedure mimicking AMI. We analyzed the release kinetics of NT-proBNP in 18 consecutive patients with hypertrophic obstructive cardiomyopathy undergoing TASH. Serum samples were collected prior to and at 15, 30, 45, 60, 75, 90, and 105 min, and 2, 4, 8, and 24h after TASH. NT-proBNP concentrations showed a continuous increase during the first 75 min with a significant percent change compared to baseline value already 15 min after TASH (105.6% [IQR 102.2-112.7]; Pvalue until the 8th h after initiation of myocardial infarction. NT-proBNP concentration increases immediately after induction of myocardial infarction proving early evidence of myocardial injury despite the decrease of the left ventricular wall stress due to the TASH related reduction of the left ventricular outflow gradient. Copyright © 2013 Elsevier B.V. All rights reserved.

The glucagon-like peptide 1 analogue Exendin-4 attenuates the nicotine-induced locomotor stimulation, accumbal dopamine release, conditioned place preference as well as the expression of locomotor sensitization in mice.

Directory of Open Access Journals (Sweden)

Emil Egecioglu

Full Text Available The gastrointestinal peptide glucagon-like peptide 1 (GLP-1 is known to regulate consummatory behavior and is released in response to nutrient ingestion. Analogues of this peptide recently emerged as novel pharmacotherapies for treatment of type II diabetes since they reduce gastric emptying, glucagon secretion as well as enhance glucose-dependent insulin secretion. The findings that GLP-1 targets reward related areas including mesolimbic dopamine areas indicate that the physiological role of GLP-1 extends beyond food intake and glucose homeostasis control to include reward regulation. The present series of experiments was therefore designed to investigate the effects of the GLP-1 receptor agonist, Exendin-4 (Ex4, on established nicotine-induced effects on the mesolimbic dopamine system in mice. Specifically, we show that treatment with Ex4, at a dose with no effect per se, attenuate nicotine-induced locomotor stimulation, accumbal dopamine release as well as the expression of conditioned place preference in mice. In accordance, Ex4 also blocks nicotine-induced expression of locomotor sensitization in mice. Given that development of nicotine addiction largely depends on the effects of nicotine on the mesolimbic dopamine system these findings indicate that the GLP-1 receptor may be a potential target for the development of novel treatment strategies for nicotine cessations in humans.

Augmented postcard

OpenAIRE

Bernik , Aleš

2012-01-01

The aim of this thesis is the examination of augmented reality technology, which allows us mixing real and virtual elements. Augmented reality is a relatively new technology which is becoming more widespread, thanks to a fairly reasonable price of smart phones. Here we presents the types of augmented reality, the necessary technology and their advantages and disadvantages, its current use in applications, and software for building augmented reality applications. The thesis is mainly focuse...

New Milk Protein-Derived Peptides with Potential Antimicrobial Activity: An Approach Based on Bioinformatic Studies

Directory of Open Access Journals (Sweden)

Bartłomiej Dziuba

2014-08-01

Full Text Available New peptides with potential antimicrobial activity, encrypted in milk protein sequences, were searched for with the use of bioinformatic tools. The major milk proteins were hydrolyzed in silico by 28 enzymes. The obtained peptides were characterized by the following parameters: molecular weight, isoelectric point, composition and number of amino acid residues, net charge at pH 7.0, aliphatic index, instability index, Boman index, and GRAVY index, and compared with those calculated for known 416 antimicrobial peptides including 59 antimicrobial peptides (AMPs from milk proteins listed in the BIOPEP database. A simple analysis of physico-chemical properties and the values of biological activity indicators were insufficient to select potentially antimicrobial peptides released in silico from milk proteins by proteolytic enzymes. The final selection was made based on the results of multidimensional statistical analysis such as support vector machines (SVM, random forest (RF, artificial neural networks (ANN and discriminant analysis (DA available in the Collection of Anti-Microbial Peptides (CAMP database. Eleven new peptides with potential antimicrobial activity were selected from all peptides released during in silico proteolysis of milk proteins.

On the blood-brain barrier to peptides: [3H]gonadotropin-releasing hormone accumulation by eighteen regions of the rat brain and by anterior pituitary

International Nuclear Information System (INIS)

Ermisch, A.; Ruehle, H.J.; Klauschenz, E.; Kretzschmar, R.

1984-01-01

After intracarotid injection of [ 3 H]gonadotropin-releasing hormone ([ 3 H]GnRH) the mean accumulation of radioactivity per unit wet weight of 18 brain samples investigated and the anterior pituitary was 0.38 +- 0.11% g -1 of the injected tracer dose. This indicates a low but measurable brain uptake of the peptide. The brain uptake of [ 3 H]GnRH in blood-brain barrier (BBB)-protected regions is 5% of that of separately investigated [ 3 H]OH. In BBB-free regions the accumulation of radioactivity was more than 25-fold higher than in BBB-protected regions. The accumulation of [ 3 H]GnRH among regions with BBB varies less than among regions with leaky endothelia. The data presented for [ 3 H]GnRH are similar to those for other peptides so far investigated. (author)

In Vitro and In Vivo Evaluation of Alexa Fluor 680-Bombesin[7–14]NH2 Peptide Conjugate, a High-Affinity Fluorescent Probe with High Selectivity for the Gastrin-Releasing Peptide Receptor

Directory of Open Access Journals (Sweden)

Lixin Ma

2007-05-01

Full Text Available Gastrin-releasing peptide (GRP receptors are overexpressed on several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. Bombesin (BBN, a 14–amino acid peptide that is an analogue of human GRP, binds to GRP receptors with very high affinity and specificity. The aim of this study was to develop a new fluorescent probe based on BBN having high tumor uptake and optimal pharmacokinetics for specific targeting and optical imaging of human breast cancer tissue. In this study, solid-phase peptide synthesis was used to produce H2N-glycylglycylglycine-BBN[7–14]NH2 peptide with the following general sequence: H2N-G-G-G-Q-W-A-V-G-H-L-M-(NH2. This conjugate was purified by reversed-phase high-performance liquid chromatography and characterized by electrospray-ionization mass spectra. The fluorescent probe Alexa Fluor 680-G-G-G-BBN[7–14]NH2 conjugate was prepared by reaction of Alexa Fluor 680 succinimidyl ester to H2N-G-G-G-BBN[7–14]NH2 in dimethylformamide (DMF. In vitro competitive binding assays, using 125I-Tyr4-BBN as the radiolabeling gold standard, demonstrated an inhibitory concentration 50% value of 7.7 ± 1.4 nM in human T-47D breast cancer cells. Confocal fluorescence microscopy images of Alexa Fluor 680-G-G-G-BBN[7–14]NH2 in human T-47D breast cancer cells indicated specific uptake, internalization, and receptor blocking of the fluorescent bioprobe in vitro. In vivo investigations in SCID mice bearing xenografted T-47D breast cancer lesions demonstrated the ability of this new conjugate to specifically target tumor tissue with high selectivity and affinity.

Postsynaptic Depolarization Enhances GABA Drive to Dorsomedial Hypothalamic Neurons through Somatodendritic Cholecystokinin Release.

Science.gov (United States)

Crosby, Karen M; Baimoukhametova, Dinara V; Bains, Jaideep S; Pittman, Quentin J

2015-09-23

Somatodendritically released peptides alter synaptic function through a variety of mechanisms, including autocrine actions that liberate retrograde transmitters. Cholecystokinin (CCK) is a neuropeptide expressed in neurons in the dorsomedial hypothalamic nucleus (DMH), a region implicated in satiety and stress. There are clear demonstrations that exogenous CCK modulates food intake and neuropeptide expression in the DMH, but there is no information on how endogenous CCK alters synaptic properties. Here, we provide the first report of somatodendritic release of CCK in the brain in male Sprague Dawley rats. CCK is released from DMH neurons in response to repeated postsynaptic depolarizations, and acts in an autocrine fashion on CCK2 receptors to enhance postsynaptic NMDA receptor function and liberate the retrograde transmitter, nitric oxide (NO). NO subsequently acts presynaptically to enhance GABA release through a soluble guanylate cyclase-mediated pathway. These data provide the first demonstration of synaptic actions of somatodendritically released CCK in the hypothalamus and reveal a new form of retrograde plasticity, depolarization-induced potentiation of inhibition. Significance statement: Somatodendritic signaling using endocannabinoids or nitric oxide to alter the efficacy of afferent transmission is well established. Despite early convincing evidence for somatodendritic release of neurohypophysial peptides in the hypothalamus, there is only limited evidence for this mode of release for other peptides. Here, we provide the first evidence for somatodendritic release of the satiety peptide cholecystokinin (CCK) in the brain. We also reveal a new form of synaptic plasticity in which postsynaptic depolarization results in enhancement of inhibition through the somatodendritic release of CCK. Copyright © 2015 the authors 0270-6474/15/3513160-11$15.00/0.

Peptide YY, neuropeptide Y and corticotrophin-releasing factor modulate gastrointestinal motility and food intake during acute stress.

Science.gov (United States)

Forbes, Sarah C; Cox, Helen M

2014-11-01

Peripheral neuropeptide Y (NPY) provides protection against the endocrine, feeding and gastrointestinal (GI) responses to stress; however, it is not yet established how it interacts with corticotrophin-releasing factor (CRF) to mediate these effects. Peptide YY (PYY) also has significant roles in GI motility and food intake but little is known about its role in stress responses. Upper GI transit, fecal pellet output (FPO) and feeding responses, and the role of CRF1 receptors, during restraint or a novel environment stress, were ascertained in PYY-/-, NPY-/- and wild type (WT) mice, with CRF and the CRF1 antagonist, antalarmin, injected intraperitoneally. Upper GI transit and FPO were significantly increased in PYY-/- mice during restraint stress. Exogenous CRF increased defecation during placement in a novel environment in WT mice through CRF1 , while CRF1 blockade reduced defecation in WT and NPY-/- mice but had no effect in PYY-/- mice. In addition, CRF1 blockade had no effect on upper GI transit in WT mice, or on food intake in PYY-/- or NPY-/- mice, but it significantly increased food intake in WT mice. Endogenous NPY appears to inhibit the colonic motor response induced by CRF1 activation, unlike PYY, while both peptides are required for CRF1 modulation of feeding behavior during stress. Overall, these results provide new insights into the mechanism by which PYY and NPY affect stress responses. © 2014 John Wiley & Sons Ltd.

Peptide Assembly-Driven Metal-Organic Framework (MOF) Motors for Micro Electric Generator

Science.gov (United States)

Ikezoe, Yasuhiro; Fang, Justin; Wasik, Tomasz L.; Uemura, Takashi; Zheng, Yongtai; Kitagawa, Susumu

2014-01-01

Peptide-MOF motors, whose motions are driven by anisotropic surface gradients created via peptide self-assembly around nanopores of MOFs, can rotate microscopic rotors and magnet fast enough to generate electric power of 0.1 µW. To make the peptide-MOF generator recyclable, a new MOF is applied as a host motor engine, which has a more rigid framework with higher H2O affinity so that peptide release occurs more efficiently via guest exchange without the destruction of MOF. PMID:25418936

Histidine-lysine peptides as carriers of nucleic acids.

Science.gov (United States)

Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

2007-03-01

With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

Indian red scorpion venom-induced augmentation of cardio-respiratory reflexes and pulmonary edema involve the release of histamine.

Science.gov (United States)

Dutta, Abhaya; Deshpande, Shripad B

2011-02-01

Pulmonary edema is a consistent feature of Mesobuthus tamulus (MBT) envenomation. Kinins, prostaglandins and other inflammatory mediators are implicated in it. Since, histamine also increases capillary permeability, this study was undertaken to evaluate whether MBT venom utilizes histamine to produce pulmonary edema and augmentation of cardio-respiratory reflexes evoked by phenylbiguanide (PBG). Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. Injection of PBG (10 μg/kg) produced apnoea, hypotension and bradycardia and the responses were augmented after exposure to venom (100 μg/kg). There was increased pulmonary water content in these animals. Pretreatment with pheniramine maleate (H₁ antagonist, 3 mg/kg) blocked both venom-induced augmentation of PBG response and pulmonary edema. In another series, compound 48/80 (mast cell depletor) was treated for 4 days then the PBG responses were elicited as before. At the end of the experiments, mast cells were counted from the peritoneal fluid. The venom-induced pulmonary edema and the augmentation of PBG reflex were not observed in compound 48/80 treated animals. Further, mast cells in the peritoneal fluid were absent in this group as compared to vehicle treated group (29 ± 7.9 cells/mm³). These observations indicate that venom-induced pulmonary edema and augmentation of PBG reflexe are mediated through mast cells by involving H₁ receptors. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gastrin-releasing peptide induces monocyte adhesion to vascular endothelium by upregulating endothelial adhesion molecules

International Nuclear Information System (INIS)

Kim, Mi-Kyoung; Park, Hyun-Joo; Kim, Yeon; Kim, Hyung Joon; Bae, Soo-Kyung; Bae, Moon-Kyoung

2017-01-01

Gastrin-releasing peptide (GRP) is a neuropeptide that plays roles in various pathophysiological conditions including inflammatory diseases in peripheral tissues; however, little is known about whether GRP can directly regulate endothelial inflammatory processes. In this study, we showed that GRP promotes the adhesion of leukocytes to human umbilical vein endothelial cells (HUVECs) and the aortic endothelium. GRP increased the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by activating nuclear factor-κB (NF-κB) in endothelial cells. In addition, GRP activated extracellular signal-regulated kinase 1/2 (ERK1/2), p38MAPK, and AKT, and the inhibition of these signaling pathways significantly reduced GRP-induced monocyte adhesion to the endothelium. Overall, our results suggested that GRP may cause endothelial dysfunction, which could be of particular relevance in the development of vascular inflammatory disorders. - Highlights: • GRP induces adhesion of monocytes to vascular endothelium. • GRP increases the expression of endothelial adhesion molecules through the activation of NF-κB. • ERK1/2, p38MAPK, and Akt pathways are involved in the GRP-induced leukocyte adhesiveness to endothelium.

Bio-composites composed of a solid free-form fabricated polycaprolactone and alginate-releasing bone morphogenic protein and bone formation peptide for bone tissue regeneration.

Science.gov (United States)

Kim, MinSung; Jung, Won-Kyo; Kim, GeunHyung

2013-11-01

Biomedical scaffolds should be designed with highly porous three-dimensional (3D) structures that have mechanical properties similar to the replaced tissue, biocompatible properties, and biodegradability. Here, we propose a new composite composed of solid free-form fabricated polycaprolactone (PCL), bone morphogenic protein (BMP-2) or bone formation peptide (BFP-1), and alginate for bone tissue regeneration. In this study, PCL was used as a mechanical supporting component to enhance the mechanical properties of the final biocomposite and alginate was used as the deterring material to control the release of BMP-2 and BFP-1. A release test revealed that alginate can act as a good release control material. The in vitro biocompatibilities of the composites were examined using osteoblast-like cells (MG63) and the alkaline phosphatase (ALP) activity and calcium deposition were assessed. The in vitro test results revealed that PCL/BFP-1/Alginate had significantly higher ALP activity and calcium deposition than the PCL/BMP-2/Alginate composite. Based on these findings, release-controlled BFP-1 could be a good growth factor for enhancement of bone tissue growth and the simple-alginate coating method will be a useful tool for fabrication of highly functional biomaterials through release-control supplementation.

Role of the hypothalamic pituitary adrenal axis in the control of the response to stress and infection

Directory of Open Access Journals (Sweden)

McCann S.M.

2000-01-01

Full Text Available The release of adrenocorticotropin (ACTH from the corticotrophs is controlled principally by vasopressin and corticotropin-releasing hormone (CRH. Oxytocin may augment the release of ACTH under certain conditions, whereas atrial natriuretic peptide acts as a corticotropin release-inhibiting factor to inhibit ACTH release by direct action on the pituitary. Glucocorticoids act on their receptors within the hypothalamus and anterior pituitary gland to suppress the release of vasopressin and CRH and the release of ACTH in response to these neuropeptides. CRH neurons in the paraventricular nucleus also project to the cerebral cortex and subcortical regions and to the locus ceruleus (LC in the brain stem. Cortical influences via the limbic system and possibly the LC augment CRH release during emotional stress, whereas peripheral input by pain and other sensory impulses to the LC causes stimulation of the noradrenergic neurons located there that project their axons to the CRH neurons stimulating them by alpha-adrenergic receptors. A muscarinic cholinergic receptor is interposed between the alpha-receptors and nitric oxidergic interneurons which release nitric oxide that activates CRH release by activation of cyclic guanosine monophosphate, cyclooxygenase, lipoxygenase and epoxygenase. Vasopressin release during stress may be similarly mediated. Vasopressin augments the release of CRH from the hypothalamus and also augments the action of CRH on the pituitary. CRH exerts a positive ultrashort loop feedback to stimulate its own release during stress, possibly by stimulating the LC noradrenergic neurons whose axons project to the paraventricular nucleus to augment the release of CRH.

Evolutionary origin and divergence of GnIH and its homologous peptides.

Science.gov (United States)

Tsutsui, Kazuyoshi; Osugi, Tomohiro

2009-03-01

Probing undiscovered hypothalamic neuropeptides that play important roles in the regulation of pituitary function in vertebrates is essential for the progress of neuroendocrinology. In 2000, we discovered a novel hypothalamic dodecapeptide inhibiting gonadotropin release in quail and termed it gonadotropin-inhibitory hormone (GnIH). GnIH acts on the pituitary and gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus via a novel G protein-coupled receptor for GnIH to inhibit gonadal development and maintenance by decreasing gonadotropin release and synthesis. Similar findings were observed in other avian species. Thus, GnIH is a key factor controlling avian reproduction. To give our findings a broader perspective, we also found GnIH homologous peptides in the hypothalamus of other vertebrates, such as mammals, reptiles, amphibians and teleosts. GnIH and its homologs share a common C-terminal LPXRFamide (X=L or Q) motif. A mammalian GnIH homolog also inhibited gonadotropin release in mammals like the GnIH action in birds. In contrast to higher vertebrates, hypophysiotropic activities of GnIH homologs were different in lower vertebrates. To clarify the evolutionary origin of GnIH and its homologs, we further sought to identify novel LPXRFamide peptides from the brain of sea lamprey and hagfish, two extant groups of the oldest lineage of vertebrates, Agnatha. In these agnathans, LPXRFamide peptide and its cDNA were identified only from the brain of hagfish. Based on these findings over the past decade, this paper summarizes the evolutionary origin and divergence of GnIH and its homologous peptides.

Peptide Hormones in the Gastrointestinal Tract

DEFF Research Database (Denmark)

Rehfeld, Jens F.

2015-01-01

Gastrointestinal hormones are peptides released from endocrine cells and neurons in the digestive tract. More than 30 hormone genes are currently known to be expressed in the gastrointestinal tract, which makes the gut the largest hormone-producing organ in the body. Modern biology makes it feasi...

Estradiol potentiation of gonadotropin-releasing hormone responsiveness in the anterior pituitary is mediated by an increase in gonadotropin-releasing hormone receptors

International Nuclear Information System (INIS)

Menon, M.; Peegel, H.; Katta, V.

1985-01-01

In order to investigate the mechanism by which 17 beta-estradiol potentiates the action of gonadotropin-releasing hormone on the anterior pituitary in vitro, cultured pituitary cells from immature female rats were used as the model system. Cultures exposed to estradiol at concentrations ranging from 10(-10) to 10(-6) mol/L exhibited a significant augmentation of luteinizing hormone release in response to a 4-hour gonadotropin-releasing hormone (10 mumol/L) challenge at a dose of 10(-9) mol/L compared to that of control cultures. The estradiol augmentation of luteinizing hormone release was also dependent on the duration of estradiol exposure. When these cultures were incubated with tritium-labeled L-leucine, an increase in incorporation of radiolabeled amino acid into total proteins greater than that in controls was observed. A parallel stimulatory effect of estradiol on iodine 125-labeled D-Ala6 gonadotropin-releasing hormone binding was observed. Cultures incubated with estradiol at different concentrations and various lengths of time showed a significant increase in gonadotropin-releasing hormone binding capacity and this increase was abrogated by cycloheximide. Analysis of the binding data showed that the increase in gonadotropin-releasing hormone binding activity was due to a change in the number of gonadotropin-releasing hormone binding sites rather than a change in the affinity. These results suggest that (1) estradiol treatment increases the number of pituitary receptors for gonadotropin-releasing hormone, (2) the augmentary effect of estradiol on luteinizing hormone release at the pituitary level might be mediated, at least in part, by the increase in the number of binding sites of gonadotropin-releasing hormone, and (3) new protein synthesis may be involved in estradiol-mediated gonadotropin-releasing hormone receptor induction

De novo design and engineering of non-ribosomal peptide synthetases

Science.gov (United States)

Bozhüyük, Kenan A. J.; Fleischhacker, Florian; Linck, Annabell; Wesche, Frank; Tietze, Andreas; Niesert, Claus-Peter; Bode, Helge B.

2018-03-01

Peptides derived from non-ribosomal peptide synthetases (NRPSs) represent an important class of pharmaceutically relevant drugs. Methods to generate novel non-ribosomal peptides or to modify peptide natural products in an easy and predictable way are therefore of great interest. However, although the overall modular structure of NRPSs suggests the possibility of adjusting domain specificity and selectivity, only a few examples have been reported and these usually show a severe drop in production titre. Here we report a new strategy for the modification of NRPSs that uses defined exchange units (XUs) and not modules as functional units. XUs are fused at specific positions that connect the condensation and adenylation domains and respect the original specificity of the downstream module to enable the production of the desired peptides. We also present the use of internal condensation domains as an alternative to other peptide-chain-releasing domains for the production of cyclic peptides.

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

NARCIS (Netherlands)

W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R. de Boer (Renske); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef (W.)

1997-01-01

textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His- ProNH2) in the middle aminoacid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds most peptides with the

 Pleiotropic action of proinsulin C-peptid

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Michał Usarek

2012-03-01

Full Text Available  Proinsulin C-peptide, released in equimolar amounts with insulin by pancreatic β cells, since its discovery in 1967 has been thought to be devoid of biological functions apart from correct insulin processing and formation of disulfide bonds between A and B chains. However, in the last two decades research has brought a substantial amount of data indicating a crucial role of C-peptide in regulating various processes in different types of cells and organs. C-peptide acts presumably via either G-protein-coupled receptor or directly inside the cell, after being internalized. However, a receptor binding this peptide has not been identified yet. This peptide ameliorates pathological changes induced by type 1 diabetes mellitus, including glomerular hyperfiltration, vessel endothelium inflammation and neuron demyelinization. In diabetic patients and diabetic animal models, C-peptide substitution in physiological doses improves the functional and structural properties of peripheral neurons and protects against hyperglycemia-induced apoptosis, promoting neuronal development, regeneration and cell survival. Moreover, it affects glycogen synthesis in skeletal muscles. In vitro C-peptide promotes disaggregation of insulin oligomers, thus enhancing its bioavailability and effects on metabolism. There are controversies concerning the biological action of C-peptide, particularly with respect to its effect on Na /K -ATPase activity. Surprisingly, the excess of circulating peptide associated with diabetes type 2 contributes to atherosclerosis development. In view of these observations, long-term, large-scale clinical investigations using C-peptide physiological doses need to be conducted in order to determine safety and health outcomes of long-term administration of C-peptide to diabetic patients.

Early events elicited by bombesin and structurally related peptides in quiescent Swiss 3T3 cells. II. Changes in Na+ and Ca2+ fluxes, Na+/K+ pump activity, and intracellular pH

International Nuclear Information System (INIS)

Mendoza, S.A.; Schneider, J.A.; Lopez-Rivas, A.; Sinnett-Smith, J.W.; Rozengurt, E.

1986-01-01

The amphibian tetradecapeptide, bombesin, and structurally related peptides caused a marked increase in ouabain-sensitive 86 Rb + uptake (a measure of Na + /K + pump activity) in quiescent Swiss 3T3 cells. This effect occurred within seconds after the addition of the peptide and appeared to be mediated by an increase in Na + entry into the cells. The effect of bombesin on Na + entry and Na + /K + pump activity was concentration dependent with half-maximal stimulation occurring at 0.3-0.4 nM. The structurally related peptides litorin, gastrin-releasing peptide, and neuromedin B also stimulated ouabain-sensitive 86 Rb + uptake; the relative potencies of these peptides in stimulating the Na + /K + pump were comparable to their potencies in increasing DNA synthesis. Bombesin increased Na + influx, at least in part, through an Na + /H + antiport. The peptide augmented intracellular pH and this effect was abolished in the absence of extracellular Na + . In addition to monovalent ion transport, bombesin and the structurally related peptides rapidly increased the efflux of 45 Ca 2+ from quiescent Swiss 3T3 cells. This Ca 2+ came from an intracellular pool and the efflux was associated with a 50% decrease in total intracellular Ca 2+ . The peptides also caused a rapid increase in cytosolic free calcium concentration. Prolonged pretreatment of Swiss 3T3 cells with phorbol dibutyrate, which causes a loss of protein kinase C activity, greatly decreased the stimulation of 86 Rb + uptake and Na + entry by bombesin implicating this phosphotransferase system in the mediation of part of these responses to bombesin. Since some activation of monovalent ion transport by bombesin was seen in phorbol dibutyrate-pretreated cells, it is likely that the peptide also stimulates monovalent ion transport by a second mechanism

Insulin release by glucagon and secretin

DEFF Research Database (Denmark)

Kofod, Hans; Andreu, D; Thams, P

1988-01-01

Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated...... the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M...... potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different....

The Role of Episodic Postprandial Peptides in Exercise-Induced Compensatory Eating.

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Gibbons, Catherine; Blundell, John E; Caudwell, Phillipa; Webb, Dominic-Luc; Hellström, Per M; Näslund, Erik; Finlayson, Graham

2017-11-01

Prolonged physical activity gives rise to variable degrees of body weight and fat loss, and is associated with variability in appetite control. Whether these effects are modulated by postprandial, peptides is unclear. We examined the role of postprandial peptide response in compensatory eating during 12 weeks of aerobic exercise and in response to high-fat, low-carbohydrate (HFLC) and low-fat, high-carbohydrate (LFHC) meals. Of the 32 overweight/obese individuals, 16 completed 12 weeks of aerobic exercise and 16 nonexercising control subjects were matched for age and body mass index. Exercisers were classified as responders or nonresponders depending on net energy balance from observed compared with expected body composition changes from measured energy expenditure. Plasma samples were collected before and after meals to compare profiles of total and acylated ghrelin, insulin, cholecystokinin, glucagon-like peptide 1 (GLP-1), and total peptide YY (PYY) between HFLC and LFHC meals, pre- and postexercise, and between groups. No differences between pre- and postintervention peptide release. Responders had greater suppression of acylated ghrelin (P exercise. Responders to exercise-induced weight loss showed greater suppression of acylated ghrelin and greater release of GLP-1 and total PYY at baseline. Therefore, episodic postprandial peptide profiles appear to form part of the pre-existing physiology of exercise responders and suggest differences in satiety potential may underlie exercise-induced compensatory eating. Copyright © 2017 Endocrine Society

Immunohistochemical localization of gastrin-releasing peptide, neuronal nitric oxide synthase and neurone-specific enolase in the uterus of the North American opossum, Didelphis virginiana.

Science.gov (United States)

Kumano, A; Sasaki, M; Budipitojo, T; Kitamura, N; Krause, W J; Yamada, J

2005-08-01

The present study has demonstrated the immunohistochemical localization of gastrin-releasing peptide (GRP), neuronal nitric oxide synthase (nNOS) and neurone-specific enolase (NSE) in the uterus of the North American opossum. Although the presence of GRP, nNOS and NSE has been reported recently in the uterus of eutherian species this is the first description of these peptides in a metatherian species. Metatherian mammals are of interest because in these species it is the prolonged lactation phase of development that is the period of primary reproductive investment rather than intrauterine development as is true of eutherian mammals. The opossum, like other marsupial species, has a very abbreviated gestation period which in Didelphis lasts only 12.5 days. GRP was localized in the cytoplasm of cells forming the surface lining epithelium and the glandular epithelium of the opossum endometrium late in pregnancy, at 11.5 days of gestation. Likewise, immunoreactivities of nNOS and NSE were found primarily within the epithelial cells of the endometrium at 11.5 days of gestation. As these peptides and enzymes appear primarily at the time of establishment of the yolk sac placenta (between day 10 and day 12.5 gestation), the present results strongly suggest that these factors may play a fundamental role in the placentation of the opossum.

Augmented Reality in Sports: Today and Tomorrow

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Zafer BOZYER

2015-08-01

Full Text Available The rapid change experienced in the field of Information Technologies makes the informati cs more tangible in daily life. Today, it became possible to encounter with the informatics applications almost all the disciplines. As a matter of course, many informatics applications are put into the practice regarding the sports discipline. Because of the condition that the power of information processing has increased and the studies on wearable technol ogies in addition to the expert system design, augmented reality (AR has become a topic which gains imp ortance in the field of sports. There are many studies that are conducted with the aim of increasing the efficiency of physical activities done in many sports branches, ensuring a more fair management of competitions and providing the opportunity for spectators to watch the competitions in a more comfortable and efficient way. In this study; the information about the current augmented reality practices th at are used in various sports branches has been given and the mobile and interactive augmented reality practices which are possible to be seen in future have been mentioned. In addition, there is an augmented reality practice which is designed with the aim of ensuring that the shoots of sports people who are interested in archery, are more stable and of ensuring that the trainings and exercises are more efficient by stating to the sports people whether he or she is in the right position for shoot which is c alled as T shape seen at the time of releasing the arrow.

Peptidomics and processing of regulatory peptides in the fruit fly Drosophila

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Dennis Pauls

2014-06-01

Full Text Available More than a decade has passed since the release of the Drosophila melanogaster genome and the first predictions of fruit fly regulatory peptides (neuropeptides and peptide hormones. Since then, mass spectrometry-based methods have fuelled the chemical characterisation of regulatory peptides, from 7 Drosophila peptides in the pre-genomic area to more than 60 today. We review the development of fruit fly peptidomics, and present a comprehensive list of the regulatory peptides that have been chemically characterised until today. We also summarise the knowledge on peptide processing in Drosophila, which has strongly profited from a combination of MS-based techniques and the genetic tools available for the fruit fly. This combination has a very high potential to study the functional biology of peptide signalling on all levels, especially with the ongoing developments in quantitative MS in Drosophila.

Plasma levels of gastrointestinal regulatory peptides in patients receiving maintenance hemodialysis

International Nuclear Information System (INIS)

Hegbrant, J.; Thysell, H.; Ekmann, R.

1991-01-01

The fasting plasma levels of nine gastrointestinal regulatory peptides were measured by radioimmunoassay in 13 stable patients with chronic renal failure, receiving hemodialysis treatment regularly and compared with those of ten healthy controls. The plasma concentrations of gastrin-releasing peptide, motilin, neurotensin, pancreatic polypeptide, peptide YY, somatostatin, substance P, and vasoactive intestinal peptide were increased. The plasma level of gastrin was not statistically different from that of the control (p=0.077). It is concluded that patients with chronic renal failure, receiving hemodialysis treatment regularly, have increased concentrations of eight of nine measured gastrointestinal regulatory peptides. The elevated levels of gastrointestinal peptides in patients with chronic renal failure may contribute to uremic gastrointestinal symptoms and dysfunctions. It is necessary to make a renal function evaluation before interpreting measured plasma levels of gastrointestinal regulatory peptides. 62 refs., 2 tabs

Cytosolic antibody delivery by lipid-sensitive endosomolytic peptide

Science.gov (United States)

Akishiba, Misao; Takeuchi, Toshihide; Kawaguchi, Yoshimasa; Sakamoto, Kentarou; Yu, Hao-Hsin; Nakase, Ikuhiko; Takatani-Nakase, Tomoka; Madani, Fatemeh; Gräslund, Astrid; Futaki, Shiroh

2017-08-01

One of the major obstacles in intracellular targeting using antibodies is their limited release from endosomes into the cytosol. Here we report an approach to deliver proteins, which include antibodies, into cells by using endosomolytic peptides derived from the cationic and membrane-lytic spider venom peptide M-lycotoxin. The delivery peptides were developed by introducing one or two glutamic acid residues into the hydrophobic face. One peptide with the substitution of leucine by glutamic acid (L17E) was shown to enable a marked cytosolic liberation of antibodies (immunoglobulins G (IgGs)) from endosomes. The predominant membrane-perturbation mechanism of this peptide is the preferential disruption of negatively charged membranes (endosomal membranes) over neutral membranes (plasma membranes), and the endosomolytic peptide promotes the uptake by inducing macropinocytosis. The fidelity of this approach was confirmed through the intracellular delivery of a ribosome-inactivation protein (saporin), Cre recombinase and IgG delivery, which resulted in a specific labelling of the cytosolic proteins and subsequent suppression of the glucocorticoid receptor-mediated transcription. We also demonstrate the L17E-mediated cytosolic delivery of exosome-encapsulated proteins.

Antioxidant, ACE-Inhibitory and antibacterial activities of Kluyveromyces marxianus protein hydrolysates and their peptide fractions

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Mahta Mirzaeia

2016-07-01

Full Text Available Background: There has been evidence that proteins are potentially excellent source of antioxidants, antihypertensive and antimicrobial peptides, and that enzymatic hydrolysis is an effective method to release these peptides from protein molecules. The functional properties of protein hydrolysates depends on the protein substrate, the specificity of the enzymes, the conditions used during proteolysis, degree of hydrolysis, and the nature of peptides released including molecular weight, amino acid composition, and hydrophobicity. Context and purpose of this study: The biomass of Kluyveromyces marxianus was considered as a source of ACE inhibitory, antioxidant and antimicrobial peptides. Results: Autolysis and enzymatic hydrolysis were completed respectively, after 96 h and 5 h. Overall, trypsin (18.52% DH and chymotrypsin (21.59% DH treatments were successful in releasing antioxidant and ACE inhibitory peptides. Autolysate sample (39.51% DH demonstrated poor antioxidant and ACE inhibitory activity compared to trypsin and chymotrypsin hydrolysates. The chymotrypsin 3-5 kDa (301.6±22.81 μM TE/mg protein and trypsin < 3 kDa (280.16±39.16 μM TE/mg protein permeate peptide fractions showed the highest DPPH radical scavenging activity. The trypsin <3 kDa permeate peptide fraction showed the highest ABTS radical scavenging (1691.1±48.68 μM TE/mg protein and ACE inhibitory (IC50=0.03±0.001 mg/mL activities. The fraction (MW=5-10 kD obtained after autolysis treatment showed antibacterial activity against St. aureus and Lis. monocytogenes in well diffusion screening. The minimum inhibitory concentration (MIC value was 13.3 mg/mLagainst St. aureus and Lis. monocytogenes calculated by turbidimetric assay and it showed bactericidal activity against St. aureus at 21.3 mg/mL protein concentration. Conclusions: Altogether, the results of this study reveal that K. marxianus proteins contain specific peptides in their sequences which can be released by

Sperm-attractant peptide influences the spermatozoa swimming behavior in internal fertilization in Octopus vulgaris.

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De Lisa, Emilia; Salzano, Anna Maria; Moccia, Francesco; Scaloni, Andrea; Di Cosmo, Anna

2013-06-15

Marine invertebrates exhibit both chemokinesis and chemotaxis phenomena, induced in most cases by the release of water-borne peptides or pheromones. In mollusks, several peptides released during egg-laying improve both male attraction and mating. Unlike other cephalopods, Octopus vulgaris adopts an indirect internal fertilization strategy. We here report on the identification and characterization of a chemoattractant peptide isolated from mature eggs of octopus females. Using two-chamber and time-lapse microscopy assays, we demonstrate that this bioactive peptide is able to increase sperm motility and induce chemotaxis by changing the octopus spermatozoa swimming behavior in a dose-dependent manner. We also provide evidence that chemotaxis in the octopus requires the presence of extracellular calcium and membrane protein phophorylation at tyrosine. This study is the first report on a sperm-activating factor in a non-free-spawning marine animal.

Combined Cell Culture-Biosensing Platform Using Vertically Aligned Patterned Peptide Nanofibers for Cellular Studies

DEFF Research Database (Denmark)

Taskin, Mehmet B.; Sasso, Luigi; Dimaki, Maria

2013-01-01

it possible to avoid a loss of sensitivity because of the diffusion of the sample. The obtained results showed that the peptide nanofibers were suitable as a cell culturing substrate for PC12 cells. The peptide nanofibers could be employed as an alternative biological material to increase the adherence......This Article presents the development of a combined cell culture–biosensing platform using vertically aligned self-assembled peptide nanofibers. Peptide nanofibers were patterned on a microchip containing gold microelectrodes to provide the cells with a 3D environment enabling them to grow...... and proliferate. Gold microelectrodes were functionalized with conductive polymers for the electrochemical detection of dopamine released from PC12 cells. The combined cell culture–biosensing platform assured a close proximity of the release site, the cells and the active surface of the sensor, thereby rendering...

B-type natriuretic peptide as prognostic marker in tetralogy of Fallot surgery.

Science.gov (United States)

Kapoor, Poonam Malhotra; Subramanian, Arun; Malik, Vishwas; Kiran, Usha; Velayoudham, Devagourou

2015-02-01

B-type natriuretic peptide has been extensively studied in patients with cardiovascular disease, but its impact on the perioperative outcome of patients with cyanotic congenital heart defects is still unclear. We assessed the perioperative changes in B-type natriuretic peptide levels and their correlation with preoperative factors and clinical outcomes in a large homogenous group of patients with tetralogy of Fallot undergoing definitive repair at a tertiary care center. A prospective study was undertaken in the cardiac operating room and intensive care unit at a single institution; 250 patients with tetralogy of Fallot undergoing intracardiac repair under cardiopulmonary bypass were studied. B-type natriuretic peptide levels were taken at 3 time points and correlated with clinical variables. Baseline B-type natriuretic peptide levels correlated with the degree of cyanosis in all 4 groups. B-type natriuretic peptide levels at 24 h after admission to the intensive care unit correlated with mortality in the adult subset of patients. B-type natriuretic peptide levels > 290 pg mL(-1) in the intensive care unit predicted an increased probability of adverse clinical outcomes. We demonstrated a rise in serum B-type natriuretic peptide levels in patients with tetralogy of Fallot undergoing definitive repair on cardiopulmonary bypass. B-type natriuretic peptide levels may be monitored to identify patients with cyanosis at increased risk of an augmented inflammatory response to cardiopulmonary bypass. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Gastrointestinal Endogenous Proteins as a Source of Bioactive Peptides - An In Silico Study

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Dave, Lakshmi A.; Montoya, Carlos A.; Rutherfurd, Shane M.; Moughan, Paul J.

2014-01-01

Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein. PMID:24901416

Gastrointestinal endogenous proteins as a source of bioactive peptides--an in silico study.

Science.gov (United States)

Dave, Lakshmi A; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

2014-01-01

Dietary proteins are known to contain bioactive peptides that are released during digestion. Endogenous proteins secreted into the gastrointestinal tract represent a quantitatively greater supply of protein to the gut lumen than those of dietary origin. Many of these endogenous proteins are digested in the gastrointestinal tract but the possibility that these are also a source of bioactive peptides has not been considered. An in silico prediction method was used to test if bioactive peptides could be derived from the gastrointestinal digestion of gut endogenous proteins. Twenty six gut endogenous proteins and seven dietary proteins were evaluated. The peptides present after gastric and intestinal digestion were predicted based on the amino acid sequence of the proteins and the known specificities of the major gastrointestinal proteases. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified. After gastrointestinal digestion (based on the in silico simulation), the total number of bioactive peptides predicted to be released ranged from 1 (gliadin) to 55 (myosin) for the selected dietary proteins and from 1 (secretin) to 39 (mucin-5AC) for the selected gut endogenous proteins. Within the intact proteins and after simulated gastrointestinal digestion, angiotensin converting enzyme (ACE)-inhibitory peptide sequences were the most frequently observed in both the dietary and endogenous proteins. Among the dietary proteins, after in silico simulated gastrointestinal digestion, myosin was found to have the highest number of ACE-inhibitory peptide sequences (49 peptides), while for the gut endogenous proteins, mucin-5AC had the greatest number of ACE-inhibitory peptide sequences (38 peptides). Gut endogenous proteins may be an important source of bioactive peptides in the gut particularly since gut endogenous proteins represent a quantitatively large and consistent source of protein.

Regulation of the mesolimbic dopamine circuit by feeding peptides.

Science.gov (United States)

Liu, S; Borgland, S L

2015-03-19

Polypeptides produced in the gastrointestinal tract, stomach, adipocytes, pancreas and brain that influence food intake are referred to as 'feeding-related' peptides. Most peptides that influence feeding exert an inhibitory effect (anorexigenic peptides). In contrast, only a few exert a stimulating effect (orexigenic peptides), such as ghrelin. Homeostatic feeding refers to when food consumed matches energy deficits. However, in western society where access to palatable energy-dense food is nearly unlimited, food is mostly consumed for non-homeostatic reasons. Emerging evidence implicates the mesocorticolimbic circuitry, including dopamine neurons of the ventral tegmental area (VTA), as a key substrate for non-homeostatic feeding. VTA dopamine neurons encode cues that predict rewards and phasic release of dopamine in the ventral striatum motivates animals to forage for food. To elucidate how feeding-related peptides regulate reward pathways is of importance to reveal the mechanisms underlying non-homeostatic or hedonic feeding. Here, we review the current knowledge of how anorexigenic peptides and orexigenic peptides act within the VTA. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Neuroactive peptides as putative mediators of antiepileptic ketogenic diets

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Carmela eGiordano

2014-04-01

Full Text Available Various ketogenic diet (KD therapies, including classic KD, medium chain triglyceride administration, low glycemic index treatment, and a modified Atkins diet, have been suggested as useful in patients affected by pharmacoresistant epilepsy. A common goal of these approaches is to achieve an adequate decrease in the plasma glucose level combined with ketogenesis, in order to mimic the metabolic state of fasting. Although several metabolic hypotheses have been advanced to explain the anticonvulsant effect of KDs, including changes in the plasma levels of ketone bodies, polyunsaturated fatty acids, and brain pH, direct modulation of neurotransmitter release, especially purinergic (i.e., adenosine and γ-aminobutyric acidergic neurotransmission, was also postulated. Neuropeptides and peptide hormones are potent modulators of synaptic activity, and their levels are regulated by metabolic states. This is the case for neuroactive peptides such as neuropeptide Y, galanin, cholecystokinin and peptide hormones such as leptin, adiponectin, and growth hormone-releasing peptides (GHRPs. In particular, the GHRP ghrelin and its related peptide des-acyl ghrelin are well-known controllers of energy homeostasis, food intake, and lipid metabolism. Notably, ghrelin has also been shown to regulate the neuronal excitability and epileptic activation of neuronal networks. Several lines of evidence suggest that GHRPs are upregulated in response to starvation and, particularly, in patients affected by anorexia and cachexia, all conditions in which also ketone bodies are upregulated. Moreover, starvation and anorexia nervosa are accompanied by changes in other peptide hormones such as adiponectin, which has received less attention. Adipocytokines such as adiponectin have also been involved in modulating epileptic activity. Thus, neuroactive peptides whose plasma levels and activity change in the presence of ketogenesis might be potential candidates for elucidating the

Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide.

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Pérez Sirkin, Daniela I; Lafont, Anne-Gaëlle; Kamech, Nédia; Somoza, Gustavo M; Vissio, Paula G; Dufour, Sylvie

2017-01-01

GnRH-associated peptide (GAP) is the C-terminal portion of the gonadotropin-releasing hormone (GnRH) preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D) structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH), despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH) structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.

Conservation of Three-Dimensional Helix-Loop-Helix Structure through the Vertebrate Lineage Reopens the Cold Case of Gonadotropin-Releasing Hormone-Associated Peptide

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Daniela I. Pérez Sirkin

2017-08-01

Full Text Available GnRH-associated peptide (GAP is the C-terminal portion of the gonadotropin-releasing hormone (GnRH preprohormone. Although it was reported in mammals that GAP may act as a prolactin-inhibiting factor and can be co-secreted with GnRH into the hypophyseal portal blood, GAP has been practically out of the research circuit for about 20 years. Comparative studies highlighted the low conservation of GAP primary amino acid sequences among vertebrates, contributing to consider that this peptide only participates in the folding or carrying process of GnRH. Considering that the three-dimensional (3D structure of a protein may define its function, the aim of this study was to evaluate if GAP sequences and 3D structures are conserved in the vertebrate lineage. GAP sequences from various vertebrates were retrieved from databases. Analysis of primary amino acid sequence identity and similarity, molecular phylogeny, and prediction of 3D structures were performed. Amino acid sequence comparison and phylogeny analyses confirmed the large variation of GAP sequences throughout vertebrate radiation. In contrast, prediction of the 3D structure revealed a striking conservation of the 3D structure of GAP1 (GAP associated with the hypophysiotropic type 1 GnRH, despite low amino acid sequence conservation. This GAP1 peptide presented a typical helix-loop-helix (HLH structure in all the vertebrate species analyzed. This HLH structure could also be predicted for GAP2 in some but not all vertebrate species and in none of the GAP3 analyzed. These results allowed us to infer that selective pressures have maintained GAP1 HLH structure throughout the vertebrate lineage. The conservation of the HLH motif, known to confer biological activity to various proteins, suggests that GAP1 peptides may exert some hypophysiotropic biological functions across vertebrate radiation.

Milk-derived angiotensin-I-converting enzymeinhibitory peptides generated by Lactobacillus delbrueckii subsp. lactis CRL 581

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Villegas Josefina M.

2014-01-01

Full Text Available Several strains of Lactobacillus helveticus and Lactobacillus delbrueckii subsp. lactis were evaluated for their ability to release angiotensin-I-converting enzyme (ACE inhibitory peptides from α-casein (α-CN and β-casein (β-CN. Casein peptides resulting from L. delbrueckii subsp. lactis CRL 581-mediated hydrolysis exhibited the highest ACE-inhibitory (ACEI activities, with values of 53 and 40% for α-CN and β-CN, respectively. The casein hydrolysates were fractionated by reversedphase high pressure liquid chromatography and some of the active peptides were identified by mass spectrometry. The fraction with the highest ACEI activity arose from β-CN and contained a mixture of the β-CN f194-206 (QEPVLGPVRGPFP and f198-206 (LGPVRGPFP peptides. Furthermore, the ACEI tripeptide IPP was identified in all β-CN hydrolysates; L. delbrueckii subsp. lactis CRL 581 produced the highest amount of this peptide. The bioactive peptides released by CRL 581 strain may be used in the formulation of functional foods and nutraceuticals, representing a healthier and natural alternative for regulating blood pressure.

Bioactive Properties of Maillard Reaction Products Generated From Food Protein-derived Peptides.

Science.gov (United States)

Arihara, K; Zhou, L; Ohata, M

Food protein-derived peptides are promising food ingredients for developing functional foods, since various bioactive peptides are released from food proteins. The Maillard reaction, which plays an important role in most processed foods, generates various chemical components during processing. Although changes of amino acids or proteins and reduced sugars by the Maillard reaction have been studied extensively, such changes of peptides by the Maillard reaction are still not resolved enough. Since food protein-derived peptides are widely utilized in many processed foods, it deserves concern and research on the changes of peptides by the Maillard reaction in foods during processing or storage. This chapter initially overviewed food protein-derived bioactive peptides. Then, Maillard reaction products generated from peptides are discussed. We focused particularly on their bioactivities. © 2017 Elsevier Inc. All rights reserved.

Release of atrial natriuretic peptide from rat myocardium in vitro: effect of minoxidil-induced hypertrophy.

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Kinnunen, P.; Taskinen, T.; Leppäluoto, J.; Ruskoaho, H.

1990-01-01

1. Ventricular hypertrophy is characterized by stimulation of ventricular synthesis of atrial natriuretic peptide (ANP). To examine the role of ventricular ANP levels in the secretion of ANP into the circulation, atrial and ventricular levels of immunoreactive-ANP (IR-ANP) as well as ANP messenger RNA (mRNA), and the release of IR-ANP from isolated perfused hearts, both before and after atrialectomy, were measured simultaneously in control and minoxidil-treated Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. 2. IR-ANP levels in the ventricles of untreated, 12 month-old SHR with severe ventricular hypertrophy were increased when compared to age-matched WKY rats. Minoxidil treatment for 8 weeks in both strains resulted in a decrease in mean arterial pressure and increases in ventricular weight to body weight ratios, plasma IR-ANP concentrations (in WKY from 133 +/- 20 to 281 +/- 34 pg ml-1, P less than 0.01; in SHR from 184 +/- 38 to 339 +/- 61 pg ml-1, P less than 0.05), and in ventricular IR-ANP contents (in WKY: 53%; in SHR: 41%). A highly significant correlation was found between ventricular IR-ANP content and ventricular weight to body weight ratio (r = 0.59, P less than 0.001, n = 26). 3. When studied in vitro, in isolated perfused heart preparations, the hypertrophied ventricular tissue after atrialectomy secreted more ANP into the perfusate than ventricles of the control hearts; ventricles contributed 28%, 22%, 18% and 15% of the total ANP release to perfusate in the minoxidil-treated SHR, control SHR, minoxidil-treated WKY and control WKY, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2141796

Mechanistic Studies on the Triggered Release of Liposomal Contents by Matrix Metalloproteinase-9

Science.gov (United States)

Elegbede, Adekunle I.; Banerjee, Jayati; Hanson, Andrea J.; Tobwala, Shakila; Ganguli, Bratati; Wang, Rongying; Lu, Xiaoning; Srivastava, D. K.; Mallik, Sanku

2009-01-01

Matrix metalloproteinases (MMPs) are a class of extracellular matrix degrading enzymes over-expressed in many cancers and contribute to the metastatic ability of the cancer cells. We have recently demonstrated that liposomal contents can be released when triggered by the enzyme MMP-9. Herein, we report our results on the mechanistic studies of the MMP-9 triggered release of the liposomal contents. We synthesized peptides containing the cleavage site for MMP-9 and conjugated them with fatty acids to prepare the corresponding lipopeptides. By employing Circular Dichroism spectroscopy, we demonstrate that the lipopeptides, when incorporated in liposomes, are de-mixed in the lipid bilayers and generate triple helical structures. MMP-9 cleaves the triple helical peptides, leading to the release of the liposomal contents. Other MMPs, which cannot hydrolyze triple helical peptides, failed to release the contents from the liposomes. We also observed that the rate and the extent of release of the liposomal contents depend on the mismatch between acyl chains of the synthesized lipopeptide and phospholipid components of the liposomes. Circular Dichroism spectroscopic studies imply that the observed differences in the release reflect the ability of the liposomal membrane to anneal the defects following the enzymatic cleavage of the liposome-incorporated lipopeptides. PMID:18642903

Cathepsin B-sensitive polymers for compartment-specific degradation and nucleic acid release.

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Chu, David S H; Johnson, Russell N; Pun, Suzie H

2012-02-10

Degradable cationic polymers are desirable for in vivo nucleic acid delivery because they offer significantly decreased toxicity over non-degradable counterparts. Peptide linkers provide chemical stability and high specificity for particular endopeptidases but have not been extensively studied for nucleic acid delivery applications. In this work, enzymatically degradable peptide-HPMA copolymers were synthesized by RAFT polymerization of HPMA with methacrylamido-terminated peptide macromonomers, resulting in polymers with low polydispersity and near quantitative incorporation of peptides. Three peptide-HPMA copolymers were evaluated: (i) pHCathK(10), containing peptides composed of the linker phe-lys-phe-leu (FKFL), a substrate of the endosomal/lysosomal endopeptidase cathepsin B, connected to oligo-(L)-lysine for nucleic acid binding, (ii) pHCath(D)K(10), containing the FKFL linker with oligo-(D)-lysine, and (iii) pH(D)Cath(D)K(10), containing all (D) amino acids. Cathepsin B degraded copolymers pHCathK(10) and pHCath(D)K(10) within 1 h while no degradation of pH(D)Cath(D)K(10) was observed. Polyplexes formed with pHCathK(10) copolymers show DNA release by 4 h of treatment with cathepsin B; comparatively, polyplexes formed with pHCath(D)K(10) and pH(D)Cath(D)K(10) show no DNA release within 8 h. Transfection efficiency in HeLa and NIH/3T3 cells were comparable between the copolymers but pHCathK(10) was less toxic. This work demonstrates the successful application of peptide linkers for degradable cationic polymers and DNA release. Copyright © 2011 Elsevier B.V. All rights reserved.

Yak milk casein as potential precursor of angiotensin I-converting enzyme inhibitory peptides based on in silico proteolysis.

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Lin, Kai; Zhang, Lan-Wei; Han, Xue; Xin, Liang; Meng, Zhao-Xu; Gong, Pi-Min; Cheng, Da-You

2018-07-15

Yak milk casein was selected as a potential precursor of bioactive peptides based on in silico analysis. Most notable among these are the angiotensin I-converting enzyme (ACE) inhibitory peptides. First, yak milk casein has high homology with cow milk casein by homologous analysis. The potential of yak milk casein for the releasing bioactive peptides was evaluated by determining the frequency of occurrence of fragments with a given activity. Through the BIOPEP database analysis, there are many bioactive peptides in yak milk casein sequences. Then, an in silico proteolysis using single or combined enzymes to obtained ACE inhibitory peptides was investigated. Cytotoxicity analysis using the online toxic prediction tool ToxinPred revealed that all in silico proteolysis derived ACE inhibitory peptides are non-cytotoxic. Overall, the present study highlights a in silico proteolysis approach to assist the yak milk casein releasing ACE inhibitory peptides and provides a guidance for the actual hydrolysis of proteins for the production of bioactive peptides. Copyright © 2018 Elsevier Ltd. All rights reserved.

Enhancing the Tourism Experience through Mobile Augmented Reality: Challenges and Prospects

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Chris D. Kounavis

2012-07-01

Full Text Available This paper discusses the use of Augmented Reality (AR applications for the needs of tourism. It describes the technology’s evolution from pilot applications into commercial mobile applications. We address the technical aspects of mobile AR application development, emphasizing the technologies that render the delivery of augmented reality content possible and experientially superior. We examine the state of the art, providing an analysis concerning the development and the objectives of each application. Acknowledging the various technological limitations hindering AR’s substantial end‐ user adoption, the paper proposes a model for developing AR mobile applications for the field of tourism, aiming to release AR’s full potential within the field.

Secondary Breast Augmentation.

Science.gov (United States)

Brown, Mitchell H; Somogyi, Ron B; Aggarwal, Shagun

2016-07-01

After studying this article, the participant should be able to: 1. Assess common clinical problems in the secondary breast augmentation patient. 2. Describe a treatment plan to correct the most common complications of breast augmentation. 3. Provide surgical and nonsurgical options for managing complications of breast augmentation. 4. Decrease the incidence of future complications through accurate assessment, preoperative planning, and precise surgical technique. Breast augmentation has been increasing steadily in popularity over the past three decades. Many of these patients present with secondary problems or complications following their primary breast augmentation. Two of the most common complications are capsular contracture and implant malposition. Familiarity and comfort with the assessment and management of these complications is necessary for all plastic surgeons. An up-to-date understanding of current devices and techniques may decrease the need to manage future complications from the current cohort of breast augmentation patients.

Physiological function of gastrin-releasing peptide and neuromedin B receptors in regulating itch scratching behavior in the spinal cord of mice.

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Devki D Sukhtankar

Full Text Available Pruritus (itch is a severe side effect associated with the use of drugs as well as hepatic and hematological disorders. Previous studies in rodents suggest that bombesin receptor subtypes i.e. receptors for gastrin-releasing peptide (GRPr and neuromedin B (NMBr differentially regulate itch scratching. However, to what degree spinal GRPr and NMBr regulate scratching evoked by intrathecally administered bombesin-related peptides is not known. The first aim of this study was to pharmacologically compare the dose-response curves for scratching induced by intrathecally administered bombesin-related peptides versus morphine, which is known to elicit itch in humans. The second aim was to determine if spinal GRPr and NMBr selectively or generally mediate scratching behavior. Mice received intrathecal injection of bombesin (0.01-0.3 nmol, GRP (0.01-0.3 nmol, NMB (0.1-1 nmol or morphine (0.3-3 nmol and were observed for one hour for scratching activity. Bombesin elicited most profound scratching over one hour followed by GRP and NMB, whereas morphine failed to evoke scratching response indicating the insensitivity of mouse models to intrathecal opioid-induced itch. Intrathecal pretreatment with GRPr antagonist RC-3095 (0.03-0.1 nmol produced a parallel rightward shift in the dose response curve of GRP-induced scratching but not NMB-induced scratching. Similarly, PD168368 (1-3 nmol only attenuated NMB but not GRP-induced scratching. Individual or co-administration of RC-3095 and PD168368 failed to alter bombesin-evoked scratching. A higher dose of RC-3095 (0.3 nmol generally suppressed scratching induced by all three peptides but also compromised motor function in the rotarod test. Together, these data indicate that spinal GRPr and NMBr independently drive itch neurotransmission in mice and may not mediate bombesin-induced scratching. GRPr antagonists at functionally receptor-selective doses only block spinal GRP-elicited scratching but the suppression of

Interactive effect of body posture on exercise-induced atrial natriuretic peptide release.

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Ray, C A; Delp, M D; Hartle, D K

1990-05-01

The purpose of this investigation was to test the hypothesis that supine exercise elicits a greater atrial natriuretic peptide (ANP) response than upright exercise because of higher atrial filling pressure attained in the supine posture. Plasma ANP concentration ([ANP]) was measured during continuous graded supine and upright exercise in eight healthy men at rest after 4 min of cycling exercise at 31, 51, and 79% of posture-specific peak oxygen uptake (VO2 peak), after 2 min of cycling at posture-specific VO2 peak, and 5 and 15 min postexercise. [ANP] was significantly increased (P less than 0.05) above rest by 64, 140, and 228% during supine cycling at 51 and 79% and VO2 peak, respectively. During upright cycling, [ANP] was significantly increased (P less than 0.05) at 79% (60%) and VO2 peak (125%). After 15 min of postexercise rest, [ANP] remained elevated (P less than 0.05) only in the supine subjects. [ANP] was 63, 79, and 75% higher (P less than 0.05) in the supine than in the upright position during cycling at 51 and 79% and VO2 peak. Systolic, diastolic, and mean blood pressures were not significantly (P greater than 0.05) different between positions in all measurement periods. Heart rates were lower (P less than 0.05) in the supine position compared with the upright position. In conclusion, these results suggest that supine exercise elicits greater ANP release independent of blood pressure and heart rate but presumably caused by greater venous return, central blood volume, and concomitant atrial filling pressure and stretch.

A Review of the Latest Advances in Encrypted Bioactive Peptides from Protein-Rich Waste

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Ailton Cesar Lemes

2016-06-01

Full Text Available Bioactive peptides are considered the new generation of biologically active regulators that not only prevent the mechanism of oxidation and microbial degradation in foods but also enhanced the treatment of various diseases and disorders, thus increasing quality of life. This review article emphasizes recent advances in bioactive peptide technology, such as: (i new strategies for transforming bioactive peptides from residual waste into added-value products; (ii nanotechnology for the encapsulation, protection and release of controlled peptides; and (iii use of techniques of large-scale recovery and purification of peptides aiming at future applications to pharmaceutical and food industries.

Peptides for Specific Intracellular Delivery and Targeting of Nanoparticles: Implications for Developing Nanoparticle-Mediated Drug Delivery

Science.gov (United States)

2010-01-01

less in size and span an array of compositions including met- als, semiconductor quantum dots (QDs), oxides, polymers , vesicles (e.g., micelles...93,98] Polymers Poly(lactic-co-glycolic acid), poly(amido amine) and dendrimers Biocompatibility, biodegradability and controlled release High drug...Secondary interactions Covalent atachment to surface ligand Thiolated peptide Biotinylated peptide Aminated peptide Sulfo-NHS Tetravalent streptavidin

The protective effect of platelet released growth factors and bone augmentation (Bio-Oss®) on ethanol impaired osteoblasts.

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Sönmez, Tolga Taha; Bayer, Andreas; Cremer, Tillman; Hock, Jennifer Vanessa Phi; Lethaus, Bernd; Kweider, Nisreen; Wruck, Christoph Jan; Drescher, Wolf; Jahr, Holger; Lippross, Sebastian; Pufe, Thomas; Tohidnezhad, Mersedeh

2017-11-01

Chronic alcohol consumption is a known limiting factor for bone healing. One promising strategy to improve bone augmentation techniques with Bio-Oss ® in oral and maxillofacial surgery might be the supportive application of platelet-concentrated biomaterials as platelet-released growth factor (PRGF). To address this matter, we performed an in vitro study investigating the protective effects of PRGF and Bio-Oss ® in ethanol (EtOH) treated osteoblasts. The SAOS-2 osteosarcoma cell line, with and without EtOH pretreatment was used. The cell viability, proliferation and alkali phosphatase activity (ALP) after application of 0%, 5% and 10% PRGF and Bio-Oss ® were assessed. The application of PRGF and Bio-Oss ® in EtOH impaired osteoblasts showed a significant beneficial influence increasing the viability of the osteoblasts in cell culture. The synergistic effect of Bio-Oss ® and 5% PRGF on the proliferation of osteoblasts was also demonstrated. Bio-Oss ® only in combination with PRGF increases the alkaline phosphatase (ALP) activity in EtOH pretreated cells. These results indicate that the simultaneous application of PRGF and Bio-Oss ® inhibits EtOH induced bone healing impairment. Furthermore, in the cells, PRGF induced a protective mechanism which might promote bone regeneration. Copyright © 2017 Elsevier GmbH. All rights reserved.

Photosystem Inspired Peptide Hybrid Catalysts

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2017-06-07

materials defined at the molecular level. We propose a novel way to make hybrid catalyst composed of inorganic nanomaterials and peptides. The...Distribution approved for public release. AF Office Of Scientific Research (AFOSR)/ IOA Arlington, Virginia 22203 Air Force Research Laboratory Air...ORGANIZATION NAME(S) AND ADDRESS(ES) SEOUL NATIONAL UNIVERSITY SNUR&DB FOUNDATION RESEARCH PARK CENTER SEOUL, 151742 KR 8. PERFORMING ORGANIZATION REPORT

Release of peptides from Fibrinogen in vitro and in vivo

International Nuclear Information System (INIS)

Weibel, S.

1986-01-01

The dissertation deals experimentally with the following problem fields: The attempt was made to obtain extremely pure, native peptides from fibrinogen with micropreparation with the help of high-pressure liquid chromatography (HPLC); a HPLC-pure antigen which could be labelled (DAT-FPA) was also to be produced and a HPLC-purified, labelled antigen (J 125 DAT-FPA) for the radioimmunoassay was to be prepared. By applying HPLC-purified FPA-material to immunise rabbits, a highly specific antibody against FPA was obtained, and the radioimmunoassay was decisively improved. Furthermore, a method with a high recovery rate specific for the A-peptides could be found. A procedure was developed which is able to separate the modifications from the plasma from one another and to prove them specifically in ng-quantities. This is the first time that the sensitive method of high-pressure liquid chromatography is used to observe the effects of the snake venom enzymes on fibrinogen over a period of 20 hrs. The kinetics of intravenously administered J 123 DAT-FPA and, in comparison, J 123 FPB β 15-42 in vivo in rabbits with the help of a scintiscanning method, was investigated and the distribution in the organism and the ways of elimination were determined. (orig./MG) [de

Augmented reality assisted surgery: a urologic training tool

Science.gov (United States)

Dickey, Ryan M; Srikishen, Neel; Lipshultz, Larry I; Spiess, Philippe E; Carrion, Rafael E; Hakky, Tariq S

2016-01-01

Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass® optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a 10-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training. PMID:26620455

Augmented reality assisted surgery: a urologic training tool.

Science.gov (United States)

Dickey, Ryan M; Srikishen, Neel; Lipshultz, Larry I; Spiess, Philippe E; Carrion, Rafael E; Hakky, Tariq S

2016-01-01

Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass ® optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a 10-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training.

Augmented reality assisted surgery: a urologic training tool

Directory of Open Access Journals (Sweden)

Ryan M Dickey

2016-01-01

Full Text Available Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass ® optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a 10-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training.

Augmented Virtual Reality Laboratory

Science.gov (United States)

Tully-Hanson, Benjamin

2015-01-01

Real time motion tracking hardware has for the most part been cost prohibitive for research to regularly take place until recently. With the release of the Microsoft Kinect in November 2010, researchers now have access to a device that for a few hundred dollars is capable of providing redgreenblue (RGB), depth, and skeleton data. It is also capable of tracking multiple people in real time. For its original intended purposes, i.e. gaming, being used with the Xbox 360 and eventually Xbox One, it performs quite well. However, researchers soon found that although the sensor is versatile, it has limitations in real world applications. I was brought aboard this summer by William Little in the Augmented Virtual Reality (AVR) Lab at Kennedy Space Center to find solutions to these limitations.

Augmented reality

Directory of Open Access Journals (Sweden)

Patrik Pucer

2011-08-01

Full Text Available Today we can obtain in a simple and rapid way most of the information that we need. Devices, such as personal computers and mobile phones, enable access to information in different formats (written, pictorial, audio or video whenever and wherever. Daily we use and encounter information that can be seen as virtual objects or objects that are part of the virtual world of computers. Everyone, at least once, wanted to bring these virtual objects from the virtual world of computers into real environments and thus mix virtual and real worlds. In such a mixed reality, real and virtual objects coexist in the same environment. The reality, where users watch and use the real environment upgraded with virtual objects is called augmented reality. In this article we describe the main properties of augmented reality. In addition to the basic properties that define a reality as augmented reality, we present the various building elements (possible hardware and software that provide an insight into such a reality and practical applications of augmented reality. The applications are divided into three groups depending on the information and functions that augmented reality offers, such as help, guide and simulator.

Gastrin-releasing peptide receptor-targeted gadolinium oxide-based multifunctional nanoparticles for dual magnetic resonance/fluorescent molecular imaging of prostate cancer

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Cui DT

2017-09-01

Full Text Available Danting Cui,1 Xiaodan Lu,1 Chenggong Yan,1 Xiang Liu,1 Meirong Hou,1 Qi Xia,2 Yikai Xu,1 Ruiyuan Liu2,3 1Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 2School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, People’s Republic of China; 3School of Biomedical Engineering, Southern Medical University, Guangzhou, People’s Republic of China Abstract: Bombesin (BBN, an analog of gastrin-releasing peptide (GRP, specifically binds to GRP receptors, which are overexpressed in human prostate cancer (PC. Here, we synthesized a BBN-modified gadolinium oxide (Gd2O3 nanoprobe containing fluorescein (Gd2O3-5(6-carboxyfluorescein [FI]-polyethylene glycol [PEG]-BBN for targeted magnetic resonance (MR/optical dual-modality imaging of PC. The Gd2O3-FI-PEG-BBN nanoparticles exhibited a relatively uniform particle size with an average diameter of 52.3 nm and spherical morphology as depicted by transmission electron microscopy. The longitudinal relaxivity (r1 of Gd2O3-FI-PEG-BBN (r1 =4.23 mM–1s–1 is comparable to that of clinically used Magnevist (Gd-DTPA. Fluorescence microscopy and in vitro cellular MRI demonstrated GRP receptor-specific and enhanced cellular uptake of the Gd2O3-FI-PEG-BBN in PC-3 tumor cells. Moreover, Gd2O3-FI-PEG-BBN showed more remarkable contrast enhancement than the corresponding nontargeted Gd2O3-FI-PEG according to in vivo MRI and fluorescent imaging. Tumor immunohistochemical analysis further demonstrated improved accumulation of the targeted nanoprobe in tumors. BBN-conjugated Gd2O3 may be a promising nanoplatform for simultaneous GRP receptor-targeted molecular cancer diagnosis and antitumor drug delivery in future clinical applications. Keywords: magnetic resonance imaging, gadolinium oxide, bombesin, gastrin-releasing peptide receptor, molecular imaging

ChemPreview: an augmented reality-based molecular interface.

Science.gov (United States)

Zheng, Min; Waller, Mark P

2017-05-01

Human computer interfaces make computational science more comprehensible and impactful. Complex 3D structures such as proteins or DNA are magnified by digital representations and displayed on two-dimensional monitors. Augmented reality has recently opened another door to access the virtual three-dimensional world. Herein, we present an augmented reality application called ChemPreview with the potential to manipulate bio-molecular structures at an atomistic level. ChemPreview is available at https://github.com/wallerlab/chem-preview/releases, and is built on top of the Meta 1 platform https://www.metavision.com/. ChemPreview can be used to interact with a protein in an intuitive way using natural hand gestures, thereby making it appealing to computational chemists or structural biologists. The ability to manipulate atoms in real world could eventually provide new and more efficient ways of extracting structural knowledge, or designing new molecules in silico. Copyright © 2017 Elsevier Inc. All rights reserved.

[The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery].

Science.gov (United States)

Baysal, Ayse; Saşmazel, Ahmet; Yildirim, Ayse; Ozyaprak, Buket; Gundogus, Narin; Kocak, Tuncer

2014-01-01

In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48h after operation. The patients enrolled into the study were divided into two groups depending on: (1) Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2) Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1) duration of mechanical ventilation ≥72h, (2) intensive care unit stay >7days, and (3) mortality. The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n=35, n=16, respectively) showed significant differences in repeated measurement time points (p=0.0001). The preoperative brain natriuretic peptide cut-off value of 125.5pgmL-1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r=0.67, p=0.0001). In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5pgmL-1 are at risk of developing low cardiac output syndrome which is an important postoperative outcome. Copyright © 2013 Sociedade

The predictive value of plasma B-type natriuretic peptide levels on outcome in children with pulmonary hypertension undergoing congenital heart surgery

Directory of Open Access Journals (Sweden)

Ayse Baysal

2014-09-01

Full Text Available Background and objectives: In children undergoing congenital heart surgery, plasma brain natriuretic peptide levels may have a role in development of low cardiac output syndrome that is defined as a combination of clinical findings and interventions to augment cardiac output in children with pulmonary hypertension. Methods: In a prospective observational study, fifty-one children undergoing congenital heart surgery with preoperative echocardiographic study showing pulmonary hypertension were enrolled. The plasma brain natriuretic peptide levels were collected before operation, 12, 24 and 48 h after operation. The patients enrolled into the study were divided into two groups depending on: (1 Development of LCOS which is defined as a combination of clinical findings or interventions to augment cardiac output postoperatively; (2 Determination of preoperative brain natriuretic peptide cut-off value by receiver operating curve analysis for low cardiac output syndrome. The secondary end points were: (1 duration of mechanical ventilation ≥72 h, (2 intensive care unit stay >7days, and (3 mortality. Results: The differences in preoperative and postoperative brain natriuretic peptide levels of patients with or without low cardiac output syndrome (n = 35, n = 16, respectively showed significant differences in repeated measurement time points (p = 0.0001. The preoperative brain natriuretic peptide cut-off value of 125.5 pg mL−1 was found to have the highest sensitivity of 88.9% and specificity of 96.9% in predicting low cardiac output syndrome in patients with pulmonary hypertension. A good correlation was found between preoperative plasma brain natriuretic peptide level and duration of mechanical ventilation (r = 0.67, p = 0.0001. Conclusions: In patients with pulmonary hypertension undergoing congenital heart surgery, 91% of patients with preoperative plasma brain natriuretic peptide levels above 125.5 pg mL−1 are at risk of developing low cardiac

Does bombesin-like peptide mediate radiation-induced anorexia and satiety?

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Aalto, Y.; Franzen, L.; Henriksson, R. [Umeaa Univ. (Sweden). Dept. of Oncology; Forsgren, S.; Kjoerell, U. [Umeaa Univ. (Sweden). Dept. of Anatomy; Funegaard, U. [Umeaa Univ. (Sweden). Dept. of Cardiology

1999-07-01

Bombesin (BN) and its mammalian counterpart gastrin-releasing peptide (GRP) act as neuroregulatory hormones and peripheral and central satiety-inducing agents. Previously, we demonstrated that irradiation induces an increase in the expression of BN/GRP in the innervation of the salivary glands in rats. We therefore carried out a study using radioimmunoassay (RIA) analysis and immunohistochemistry to examine whether saliva contains BN and whether irradiation affects the BN release to saliva in rats. Immunoreactivity for BN was detected not only in the innervation of the parenchyma but also in the duct cells and in the lumina of the ducts, suggesting entrance of BN into saliva. The RIA analysis confirmed that rat saliva contains a BN-like peptide. The observation shows that saliva contains this peptide but that there is no significant increase following the radiation schedule used. Nevertheless, the occurrence of an enhanced expression of BN in different peripheral tissues such as the salivary and laryngeal glands should be taken into consideration when discussing the clinically important problem of reduced food intake and anorexia in cancer patients. (orig.)

Does bombesin-like peptide mediate radiation-induced anorexia and satiety?

International Nuclear Information System (INIS)

Aalto, Y.; Franzen, L.; Henriksson, R.; Forsgren, S.; Kjoerell, U.; Funegaard, U.

1999-01-01

Bombesin (BN) and its mammalian counterpart gastrin-releasing peptide (GRP) act as neuroregulatory hormones and peripheral and central satiety-inducing agents. Previously, we demonstrated that irradiation induces an increase in the expression of BN/GRP in the innervation of the salivary glands in rats. We therefore carried out a study using radioimmunoassay (RIA) analysis and immunohistochemistry to examine whether saliva contains BN and whether irradiation affects the BN release to saliva in rats. Immunoreactivity for BN was detected not only in the innervation of the parenchyma but also in the duct cells and in the lumina of the ducts, suggesting entrance of BN into saliva. The RIA analysis confirmed that rat saliva contains a BN-like peptide. The observation shows that saliva contains this peptide but that there is no significant increase following the radiation schedule used. Nevertheless, the occurrence of an enhanced expression of BN in different peripheral tissues such as the salivary and laryngeal glands should be taken into consideration when discussing the clinically important problem of reduced food intake and anorexia in cancer patients. (orig.)

Preservation of peptide moieties in three Spanish sulfur-rich Tertiary kerogens

Energy Technology Data Exchange (ETDEWEB)

Rio, J.C. del [Consejo Superior de Investigaciones Cientificas, Seville (Spain). Inst. de Recursos Naturales y Agrobiologia; Olivella, M.A.; Heras, F.X.D. de las [Escola Universitaria Politecnica de Manresa, Catalonia (Spain); Knicker, H. [Technische Universitaet Muenchen (Germany). Lehrstuhl fuer Bodenkunde

2004-09-01

Thermochemolysis with tetramethylammonium hydroxide (TMAH) and solid-state {sup 15}N NMR were utilized for the characterization of refractory organic nitrogen in Tertiary Spanish kerogens. The samples included sulfur-rich oil shales from the Ribesalbes (Serravallian), Libros (Tortonian) and Cerdanya (Tortonian) basins. Analysis using solid state {sup 15}N NMR showed that part of the refractory nitrogen in the kerogens corresponds to amide groups. Moreover, the release of amino acid derivatives after pyrolysis in the presence of TMAH indicated that this amide-N arose from peptide moieties. The amino acids released from the kerogens were dominated by high amounts of glycine and alanine. Minor amounts of aspartic acid, serine, {alpha}-aminobutyric acid and other unidentified amino acids were also detected. Because proteinaceous structures, including small peptides, are generally considered as being highly sensitive to diagenetic degradation, encapsulation of labile peptide material into aliphatic structures in S-rich kerogens (probably via lipid sulfurization) has been proposed to explain the survival of these moieties. Substantial amounts of fatty acids (as methyl esters) were also released from all the kerogens after pyrolysis/TMAH, indicating their highly aliphatic character. The production of both fatty acids and amino acids from the kerogens supports the encapsulation process. (author)

Stabilization and delivery approaches for protein and peptide pharmaceuticals: an extensive review of patents.

Science.gov (United States)

Swain, Suryakanta; Mondal, Debanik; Beg, Sarwar; Patra, Chinam Niranjan; Dinda, Subas Chandra; Sruti, Jammula; Rao, Muddana Eswara Bhanoji

2013-04-01

Proteins and peptides are the building blocks of human body and act as the arsenal to combat against the invading pathogenic organisms for treatment and management of diseases. Majority of such biomacromolecules are synthesized by the human body itself. However, entry of disease causing pathogens causes misleading in the synthesis of desired proteins for antibody formation. In such alarming situations, the delivery of requisite protein and peptide from external source helps in augmenting the body's immunity. The major drawbacks underlying poor biopharmaceutical performance of high molecular weight protein and peptide drugs are due to poor oral absorption, formulation stability, degradation in the gastric milieu, susceptible to presystemic metabolism. Numerous literature recounts the application of myriad drug delivery strategies for the effective delivery of protein and peptides viz. parentral, oral, transdermal, nasal, pulmonary, rectal, buccal and ocular drug delivery systems. There are many reviews on various delivery strategies for protein and peptide pharmaceuticals, but the present review article provides a bird's eye view on various novel drug delivery systems used for enhanced delivery of protein and peptide pharmaceuticals in the light of patent literature. Apart from this, the present manuscript endeavor provides idea on possible causes and major degradation pathways responsible for poor stability of protein and peptide drugs along with recent market instances on them utilizing novel drug delivery systems.

[Ala12]MCD peptide: a lead peptide to inhibitors of immunoglobulin E binding to mast cell receptors.

Science.gov (United States)

Buku, A; Condie, B A; Price, J A; Mezei, M

2005-09-01

An effort was made to discover mast cell degranulating (MCD) peptide analogs that bind with high affinity to mast cell receptors without triggering secretion of histamine or other mediators of the allergic reaction initiated by immunoglobulin E (IgE) after mast cell activation. Such compounds could serve as inhibitors of IgE binding to mast cell receptors. An alanine scan of MCD peptide reported previously showed that the analog [Ala12]MCD was 120-fold less potent in histamine-releasing activity and fivefold more potent in binding affinity to mast cell receptors than the parent MCD peptide. Because this analog showed marginal intrinsic activity and good binding affinity it was subsequently tested in the present study as an IgE inhibitor. In contrast to MCD peptide, [Ala12]MCD showed a 50% inhibition of IgE binding to the Fc epsilon RI alpha mast cell receptor by using rat basophilic leukemia (RBL-2H3) mast cells and fluorescence polarization. Furthermore, in a beta-hexosaminidase secretory assay, the peptide also showed a 50% inhibition of the secretion of this enzyme caused by IgE. An attempt was made to relate structural changes and biologic differences between the [Ala12]MCD analog and the parent MCD peptide. The present results show that [Ala12]MCD may provide a base for designing agents to prevent IgE/Fc epsilon RI alpha interactions and, consequently, allergic conditions.

Generation of L cells in mouse and human small intestine organoids

DEFF Research Database (Denmark)

Petersen, Natalia; Reimann, Frank; Bartfeld, Sina

2014-01-01

Upon a nutrient challenge, L cells produce glucagon-like peptide 1 (GLP-1), a powerful stimulant of insulin release. Strategies to augment endogenous GLP-1 production include promoting L-cell differentiation and increasing L-cell number. Here we present a novel in vitro platform to generate funct...

Examining the Effectiveness of Augmented Reality Applications in Education: A Meta-Analysis

Science.gov (United States)

Tekedere, Hakan; Göke, Hanife

2016-01-01

In this study, the purpose is examining the reviews released on augmented reality applications in education, merging the results obtained in the studies that are independent from each other, and providing a new viewpoint for the studies that will be conducted in the future. The meta-analysis method has been used in the study. 15 out of 171…

DAMPD: A manually curated antimicrobial peptide database

KAUST Repository

Seshadri Sundararajan, Vijayaraghava

2011-11-21

The demand for antimicrobial peptides (AMPs) is rising because of the increased occurrence of pathogens that are tolerant or resistant to conventional antibiotics. Since naturally occurring AMPs could serve as templates for the development of new anti-infectious agents to which pathogens are not resistant, a resource that contains relevant information on AMP is of great interest. To that extent, we developed the Dragon Antimicrobial Peptide Database (DAMPD, http://apps.sanbi.ac.za/dampd) that contains 1232 manually curated AMPs. DAMPD is an update and a replacement of the ANTIMIC database. In DAMPD an integrated interface allows in a simple fashion querying based on taxonomy, species, AMP family, citation, keywords and a combination of search terms and fields (Advanced Search). A number of tools such as Blast, ClustalW, HMMER, Hydrocalculator, SignalP, AMP predictor, as well as a number of other resources that provide additional information about the results are also provided and integrated into DAMPD to augment biological analysis of AMPs. The Author(s) 2011. Published by Oxford University Press.

DAMPD: A manually curated antimicrobial peptide database

KAUST Repository

Seshadri Sundararajan, Vijayaraghava; Gabere, Musa Nur; Pretorius, Ashley; Adam, Saleem; Christoffels, Alan; Lehvaslaiho, Minna; Archer, John A.C.; Bajic, Vladimir B.

2011-01-01

The demand for antimicrobial peptides (AMPs) is rising because of the increased occurrence of pathogens that are tolerant or resistant to conventional antibiotics. Since naturally occurring AMPs could serve as templates for the development of new anti-infectious agents to which pathogens are not resistant, a resource that contains relevant information on AMP is of great interest. To that extent, we developed the Dragon Antimicrobial Peptide Database (DAMPD, http://apps.sanbi.ac.za/dampd) that contains 1232 manually curated AMPs. DAMPD is an update and a replacement of the ANTIMIC database. In DAMPD an integrated interface allows in a simple fashion querying based on taxonomy, species, AMP family, citation, keywords and a combination of search terms and fields (Advanced Search). A number of tools such as Blast, ClustalW, HMMER, Hydrocalculator, SignalP, AMP predictor, as well as a number of other resources that provide additional information about the results are also provided and integrated into DAMPD to augment biological analysis of AMPs. The Author(s) 2011. Published by Oxford University Press.

Nano-galvanic coupling for enhanced Ag+ release in ZrCN-Ag films : Antibacterial application

NARCIS (Netherlands)

Calderon, S.; Ferreri, I.; Henriques, M.; De Hosson, J. T. M.; Cavaleiro, A.; Carvalho, S.

2016-01-01

The antibacterial properties of materials developed for medical devices with embedded silver nanoparticles are enhanced by controlling the release of silver ions. In this study, a simple experimental procedure for the augmentation of the silver ion release from ZrCN-Ag coatings is described. The

Enzyme-Assisted Discovery of Antioxidant Peptides from Edible Marine Invertebrates: A Review.

Science.gov (United States)

Chai, Tsun-Thai; Law, Yew-Chye; Wong, Fai-Chu; Kim, Se-Kwon

2017-02-16

Marine invertebrates, such as oysters, mussels, clams, scallop, jellyfishes, squids, prawns, sea cucumbers and sea squirts, are consumed as foods. These edible marine invertebrates are sources of potent bioactive peptides. The last two decades have seen a surge of interest in the discovery of antioxidant peptides from edible marine invertebrates. Enzymatic hydrolysis is an efficient strategy commonly used for releasing antioxidant peptides from food proteins. A growing number of antioxidant peptide sequences have been identified from the enzymatic hydrolysates of edible marine invertebrates. Antioxidant peptides have potential applications in food, pharmaceuticals and cosmetics. In this review, we first give a brief overview of the current state of progress of antioxidant peptide research, with special attention to marine antioxidant peptides. We then focus on 22 investigations which identified 32 antioxidant peptides from enzymatic hydrolysates of edible marine invertebrates. Strategies adopted by various research groups in the purification and identification of the antioxidant peptides will be summarized. Structural characteristic of the peptide sequences in relation to their antioxidant activities will be reviewed. Potential applications of the peptide sequences and future research prospects will also be discussed.

Amphiphilic cationic peptides mediate cell adhesion to plastic surfaces.

Science.gov (United States)

Rideout, D C; Lambert, M; Kendall, D A; Moe, G R; Osterman, D G; Tao, H P; Weinstein, I B; Kaiser, E T

1985-09-01

Four amphiphilic peptides, each with net charges of +2 or more at neutrality and molecular weights under 4 kilodaltons, were found to mediate the adhesion of normal rat kidney fibroblasts to polystyrene surfaces. Two of these peptides, a model for calcitonin (peptide 1, MCT) and melittin (peptide 2, MEL), form amphiphilic alpha-helical structures at aqueous/nonpolar interfaces. The other two, a luteinizing hormone-releasing hormone model (peptide 3, LHM) and a platelet factor model (peptide 4, MPF) form beta-strand structures in amphiphilic environments. Although it contains only 10 residues, LHM mediated adhesion to surfaces coated with solutions containing as little as 10 pmoles/ml of peptide. All four of these peptides were capable of forming monolayers at air-buffer interfaces with collapse pressures greater than 20 dynes/cm. None of these four peptides contains the tetrapeptide sequence Arg-Gly-Asp-Ser, which has been associated with fibronectin-mediated cell adhesion. Ten polypeptides that also lacked the sequence Arg-Gly-Asp-Ser but were nonamphiphilic and/or had net charges less than +2 at neutrality were all incapable of mediating cell adhesion (Pierschbacher and Ruoslahti, 1984). The morphologies of NRK cells spread on polystyrene coated with peptide LHM resemble the morphologies on fibronectin-coated surfaces, whereas cells spread on surfaces coated with MCT or MEL exhibit strikingly different morphologies. The adhesiveness of MCT, MEL, LHM, and MPF implies that many amphiphilic cationic peptides could prove useful as well defined adhesive substrata for cell culture and for studies of the mechanism of cell adhesion.

The role of antimicrobial peptides in animal defenses

Science.gov (United States)

Hancock, Robert E. W.; Scott, Monisha G.

2000-08-01

It is becoming clear that the cationic antimicrobial peptides are an important component of the innate defenses of all species of life. Such peptides can be constitutively expressed or induced by bacteria or their products. The best peptides have good activities vs. a broad range of bacterial strains, including antibiotic-resistant isolates. They kill very rapidly, do not easily select resistant mutants, are synergistic with conventional antibiotics, other peptides, and lysozyme, and are able to kill bacteria in animal models. It is known that bacterial infections, especially when treated with antibiotics, can lead to the release of bacterial products such as lipopolysaccharide (LPS) and lipoteichoic acid, resulting in potentially lethal sepsis. In contrast to antibiotics, the peptides actually prevent cytokine induction by bacterial products in tissue culture and human blood, and they block the onset of sepsis in mouse models of endotoxemia. Consistent with this, transcriptional gene array experiments using a macrophage cell line demonstrated that a model peptide, CEMA, blocks the expression of many genes whose transcription was induced by LPS. The peptides do this in part by blocking LPS interaction with the serum protein LBP. In addition, CEMA itself has a direct effect on macrophage gene expression. Because cationic antimicrobial peptides are induced by LPS and are able to dampen the septic response of animal cells to LPS, we propose that, in addition to their role in direct and lysozyme-assisted killing of microbes, they have a role in feedback regulation of cytokine responses. We are currently developing variant peptides as therapeutics against antibiotic-resistant infections.

One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer.

Science.gov (United States)

Luginbuhl, Kelli M; Schaal, Jeffrey L; Umstead, Bret; Mastria, Eric M; Li, Xinghai; Banskota, Samagya; Arnold, Susan; Feinglos, Mark; D'Alessio, David; Chilkoti, Ashutosh

2017-01-01

Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 receptor has a short half-live owing to enzymatic inactivation and rapid clearance. Here, we show that a subcutaneous depot formed after a single injection of GLP1 recombinantly fused to a thermosensitive elastin-like polypeptide results in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics leads to 10 days of glycemic control in three different mouse models of diabetes, as well as to the reduction of glycosylated hemoglobin levels and weight gain in ob/ob mice treated once weekly for 8 weeks. Our results suggest that the optimized GLP1 formulation could enhance therapeutic outcomes by eliminating peak-and-valley pharmacokinetics and improving overall safety and tolerability. The design principles that we established should be broadly applicable for improving the pharmacological performance of other peptide and protein therapeutics.

Dual-coating of liposomes as encapsulating matrix of antimicrobial peptides: Development and characterization

Science.gov (United States)

Gomaa, Ahmed I.; Martinent, Cynthia; Hammami, Riadh; Fliss, Ismail; Subirade, Muriel

2017-11-01

Abstract Antimicrobial peptides have been proposed as a potential biopreservatives in pharmaceutical research and agribusiness. However, many limitations hinder their utilization, such as their vulnerability to proteolytic digestion and their potential interaction with other food ingredients in complex food systems. One approach to overcome such problems is developing formulations entrapping and thereby protecting the antimicrobial peptides. Liposome encapsulation is a strategy that could be implemented to combine protection of the antimicrobial activity of the peptides from proteolytic enzymes and the controlled release of the encapsulated active ingredients. The objective of this study was to develop dual-coated food grade liposome formulations for oral administration of bacteriocins. The formulations were developed from anionic and cationic phospholipids as models of negatively and positively charged liposomes, respectively. Liposomes were prepared by the hydration of lipid films. Subsequently, the liposomes were coated with two layers comprising a biopolymer network (pectin) and whey proteins (WPI) in order to further improve their stability and enable the gradual release of the developed liposomes. Liposomes were characterized for their size, charge, molecular structure, morphology, encapsulation efficiency and release. The results of FTIR, zeta potential, size distribution and transmission electron microscopy confirmed that the liposomes were efficiently coated. Ionic interactions were involved in the stabilization of the positively charged liposome formulations. Negatively charge liposome formulations were stabilized through weak interactions. The release study proved the efficiency of dual coating on the protection of liposomes against gastrointestinal digestion. This work is the first to study the encapsulation of antimicrobial peptides in dual-coated liposomes. Furthermore, the work successfully encapsulated MccJ25 in both negative and positive liposome

Membrane interactions and biological activity of antimicrobial peptides from Australian scorpion.

Science.gov (United States)

Luna-Ramírez, Karen; Sani, Marc-Antoine; Silva-Sanchez, Jesus; Jiménez-Vargas, Juana María; Reyna-Flores, Fernando; Winkel, Kenneth D; Wright, Christine E; Possani, Lourival D; Separovic, Frances

2014-09-01

UyCT peptides are antimicrobial peptides isolated from the venom of the Australian scorpion. The activity of the UyCT peptides against Gram positive and Gram negative bacteria and red blood cells was determined. The membrane interactions of these peptides were evaluated by dye release (DR) of the fluorophore calcein from liposomes and isothermal titration calorimetry (ITC); and their secondary structure was determined by circular dichroism (CD). Three different lipid systems were used to mimic red blood cells, Escherichia coli and Staphylococcus aureus membranes. UyCT peptides exhibited broad spectrum antimicrobial activity with low MIC for S. aureus and multi-drug resistant Gram negative strains. Peptide combinations showed some synergy enhancing their potency but not hemolytic activity. The UyCT peptides adopted a helical structure in lipid environments and DR results confirmed that the mechanism of action is by disrupting the membrane. ITC data indicated that UyCT peptides preferred prokaryotic rather than eukaryotic membranes. The overall results suggest that UyCT peptides could be pharmaceutical leads for the treatment of Gram negative multiresistant bacterial infections, especially against Acinetobacter baumanni, and candidates for peptidomimetics to enhance their potency and minimize hemolysis. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova. © 2013.

The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation.

Science.gov (United States)

Wong, Chun Y; Al-Salami, Hani; Dass, Crispin R

2017-12-01

Therapeutic peptides are conventionally administered via subcutaneous injection. Chitosan-based nanoparticles are gaining increased attention for their ability to serve as a carrier for oral delivery of peptides and vaccination. They offered superior biocompatibiltiy, controlled drug release profile and facilitated gastrointestinal (GI) absorption. The encapsulated peptides can withstand enzymatic degradation and various pH. Chitosan-based nanoparticles can also be modified by ligand conjugation to the surface of nanoparticle for transcellular absorption and specific-targeted delivery of macromolecules to the tissue of interest. Current research suggests that chitosan-based nanoparticles can deliver therapeutic peptide for the treatment of several medical conditions such as diabetes, bacterial infection and cancer. This review summarises the role of chitosan in oral nanoparticle delivery and identifies the clinical application of peptide-loaded chitosan-based nanoparticles.

Beta-amyloid peptides undergo regulated co-secretion with neuropeptide and catecholamine neurotransmitters.

Science.gov (United States)

Toneff, Thomas; Funkelstein, Lydiane; Mosier, Charles; Abagyan, Armen; Ziegler, Michael; Hook, Vivian

2013-08-01

Beta-amyloid (Aβ) peptides are secreted from neurons, resulting in extracellular accumulation of Aβ and neurodegeneration of Alzheimer's disease. Because neuronal secretion is fundamental for the release of neurotransmitters, this study assessed the hypothesis that Aβ undergoes co-release with neurotransmitters. Model neuronal-like chromaffin cells were investigated, and results illustrate regulated, co-secretion of Aβ(1-40) and Aβ(1-42) with peptide neurotransmitters (galanin, enkephalin, and NPY) and catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). Regulated secretion from chromaffin cells was stimulated by KCl depolarization and nicotine. Forskolin, stimulating cAMP, also induced co-secretion of Aβ peptides with peptide and catecholamine neurotransmitters. These data suggested the co-localization of Aβ with neurotransmitters in dense core secretory vesicles (DCSV) that store and secrete such chemical messengers. Indeed, Aβ was demonstrated to be present in DCSV with neuropeptide and catecholamine transmitters. Furthermore, the DCSV organelle contains APP and its processing proteases, β- and γ-secretases, that are necessary for production of Aβ. Thus, Aβ can be generated in neurotransmitter-containing DCSV. Human IMR32 neuroblastoma cells also displayed regulated secretion of Aβ(1-40) and Aβ(1-42) with the galanin neurotransmitter. These findings illustrate that Aβ peptides are present in neurotransmitter-containing DCSV, and undergo co-secretion with neuropeptide and catecholamine neurotransmitters that regulate brain functions. Copyright © 2013 Elsevier Inc. All rights reserved.

B-type natriuretic peptides. A diagnostic breakthrough in heart failure.

Science.gov (United States)

McCullough, P A

2003-04-01

B-type natriuretic peptide (BNP) is a neurohormone synthesized in the cardiac ventricles, which is released as N-terminal pro-brain natriuretic peptide (NT-proBNP) and then enzymatically cleaved in to the NT fragment and the immunoreactive BNP. Both tests have been used to identify patients with congestive heart failure (CHF). Important considerations for these tests include their half-lives in plasma, dependence on renal function for clearance, and the interpretation of their units of measure. In general, a BNP level below 100 pg/mL has strong negative predictive value in the assessment of patients with dyspnea caused by a disorder other than CHF. In addition, BNP levels can be used to gauge the effect of short-term treatment of acutely decompensated heart failure, and the peptide has been shown to be a reliable independent predictor of sudden cardiac death. In the absence of renal dysfunction NT-proBNP has also been shown to be an independent predictor of sudden death in CHF patients. Because both a large area of myonecrosis or concomitant left ventricular failure are related to prognosis in acute coronary syndromes, B-type natriuretic peptides have also been linked to outcomes in this condition. This article describes the physiology and timing of release of B-type natriuretic peptides and the rationale for their use in the following settings: 1) evaluation of decompensated CHF, 2) screening for chronic CHF, 3) prognosis of CHF and sudden death, and 4) prognosis in acute coronary syndromes with inferred left ventricular dysfunction.

Presence of chromogranin-derived antimicrobial peptides in plasma during coronary artery bypass surgery and evidence of an immune origin of these peptides.

Science.gov (United States)

Tasiemski, Aurélie; Hammad, Hamida; Vandenbulcke, Franck; Breton, Christophe; Bilfinger, Thomas J; Pestel, Joel; Salzet, Michel

2002-07-15

Chromogranin A (CGA) and chromogranin B (CGB) are acidic proteins stored in secretory organelles of endocrine cells and neurons. In addition to their roles as helper proteins in the packaging of peptides, they may serve as prohormones to generate biologically active peptides such as vasostatin-1 and secretolytin. These molecules derived from CGA and CGB, respectively, possess antimicrobial properties. The present study demonstrates that plasmatic levels of both vasostatin-1 and secretolytin increase during surgery in patients undergoing cardiopulmonary bypass (CPB). Vasostatin-1 and secretolytin, initially present in plasma at low levels, are released just after skin incision. Consequently, they can be added to enkelytin, an antibacterial peptide derived from proenkephalin A, for the panoply of components acting as a first protective barrier against hypothetical invasion of pathogens, which may occur during surgery. CGA and CGB, more commonly viewed as markers for endocrine and neuronal cells, were also found to have an immune origin. RNA messengers coding for CGB were amplified by reverse transcription-polymerase chain reaction in human monocytes, and immunocytochemical analysis by confocal microscopy revealed the presence of CGA or CGB or both in monocytes and neutrophils. A combination of techniques including confocal microscopic analysis, mass spectrometry measurement, and antibacterial tests allowed for the identification of the positive role of interleukin 6 (IL-6) in the secretolytin release from monocytes in vitro. Because IL-6 release is known to be strongly enhanced during CPB, we suggest a possible relationship between IL-6 and the increased level of secretolytin in patients undergoing CPB.

Glucagon and glucagon-like peptides 1 and 2

DEFF Research Database (Denmark)

Holst, Jens Juul

2010-01-01

amino acid precursor, proglucagon, leaving behind proglucagon fragments (PG 1-30 and PG 72-158, the so-called major proglucagon fragment (MPGF)) that are probably inactive, the intestinal processing leads to the formation of glicentin (PG 1-69; action uncertain) and glucagon-like peptides 1 (PG 78....... After their release, the hormones are eliminated mainly in the kidneys, but both GLP-2 and in particular GLP-1, but not glucagon, are metabolized both locally and in the circulation and liver by dipeptidyl peptidase 4 (DPP-4) which inactivates the peptides, suggesting that GLP-1 acts locally rather than...

AUGMENTED REALITY

DEFF Research Database (Denmark)

Skov, Kirsten; Bahn, Anne Louise

2017-01-01

Projektets grundlæggende idé er udvikling af visuel, æstetisk læring med Augmented Reality, hvor intentionen er at bidrage med konkrete undersøgelser og udforskning af begrebet Augmented Reality – herunder koblingen mellem det analoge og digitale i forhold til læring, multimodalitet og it...

Intelligent "Peptide-Gathering Mechanical Arm" Tames Wild "Trojan-Horse" Peptides for the Controlled Delivery of Cancer Nanotherapeutics.

Science.gov (United States)

Shi, Nian-Qiu; Li, Yan; Zhang, Yong; Shen, Nan; Qi, Ling; Wang, Shu-Ran; Qi, Xian-Rong

2017-12-06

Cell-penetrating peptides (CPPs), also called "Trojan-Horse" peptides, have been used for facilitating intracellular delivery of numerous diverse cargoes and even nanocarriers. However, the lack of targeting specificity ("wildness" or nonselectivity) of CPP-nanocarriers remains an intractable challenge for many in vivo applications. In this work, we used an intelligent "peptide-gathering mechanical arm" (Int PMA) to curb CPPs' wildness and enhance the selectivity of R 9 -liposome-based cargo delivery for tumor targeting. The peptide NGR, serving as a cell-targeting peptide for anchoring, and peptide PLGLAG, serving as a substrate peptide for deanchoring, were embedded in the Int PMA motif. The Int PMA construct was designed to be sensitive to tumor microenvironmental stimuli, including aminopeptidase N (CD13) and matrix metalloproteinases (MMP-2/9). Moreover, Int PMA could be specifically recognized by tumor tissues via CD13-mediated anchoring and released for cell entry by MMP-2/9-mediated deanchoring. To test the Int PMA design, a series of experiments were conducted in vitro and in vivo. Functional conjugates Int PMA-R 9 -poly(ethylene glycol) (PEG) 2000 -distearoylphosphatidyl-ethanolamine (DSPE) and R 9 -PEG 2000 -DSPE were synthesized by Michael addition reaction and were characterized by thin-layer chromatography and matrix-assisted laser desorption ionization-time-of-flight mass spectrometry. The Int PMA-R 9 -modified doxorubicin-loaded liposomes (Int PMA-R 9 -Lip-DOX) exhibited a proper particle diameter (approximately 155 nm) with in vitro sustained release characteristics. Cleavage assay showed that Int PMA-R 9 peptide molecules could be cleaved by MMP-2/9 for completion of deanchoring. Flow cytometry and confocal microscopy studies indicated that Int PMA-R 9 -Lip-DOX can respond to both endogenous and exogenous stimuli in the presence/absence of excess MMP-2/9 and MMP-2/9 inhibitor (GM6001) and effectively function under competitive receptor

Tracking for Outdoor Mobile Augmented Reality: Further development of the Zion Augmented Reality Application

OpenAIRE

Strand, Tor Egil Riegels

2008-01-01

This report deals with providing tracking to an outdoor mobile augmented reality system and the Zion Augmented Reality Application. ZionARA is meant to display a virtual recreation of a 13th century castle on the site it once stood through an augmented reality Head Mounted Display. Mobile outdoor augmented/mixed reality puts special demands on what kind of equipment is practical. After briefly evaluating the different existing tracking methods, a solution based on GPS and an augmented inertia...

The membranotropic activity of N-terminal peptides from the pore ...

Indian Academy of Sciences (India)

how these water-soluble proteins bind, oligomerize and eventually disrupt target .... Creek, CA, USA), using UV detection at 220 nm. The identity of the peptides ... leakage of dye was negligible under these conditions. Maximum release was ...

Cathelicidin host defence peptide augments clearance of pulmonary Pseudomonas aeruginosa infection by its influence on neutrophil function in vivo.

Directory of Open Access Journals (Sweden)

Paula E Beaumont

Full Text Available Cathelicidins are multifunctional cationic host-defence peptides (CHDP; also known as antimicrobial peptides and an important component of innate host defence against infection. In addition to microbicidal potential, these peptides have properties with the capacity to modulate inflammation and immunity. However, the extent to which such properties play a significant role during infection in vivo has remained unclear. A murine model of acute P. aeruginosa lung infection was utilised, demonstrating cathelicidin-mediated enhancement of bacterial clearance in vivo. The delivery of exogenous synthetic human cathelicidin LL-37 was found to enhance a protective pro-inflammatory response to infection, effectively promoting bacterial clearance from the lung in the absence of direct microbicidal activity, with an enhanced early neutrophil response that required both infection and peptide exposure and was independent of native cathelicidin production. Furthermore, although cathelicidin-deficient mice had an intact early cellular inflammatory response, later phase neutrophil response to infection was absent in these animals, with significantly impaired clearance of P. aeruginosa. These findings demonstrate the importance of the modulatory properties of cathelicidins in pulmonary infection in vivo and highlight a key role for cathelicidins in the induction of protective pulmonary neutrophil responses, specific to the infectious milieu. In additional to their physiological roles, CHDP have been proposed as future antimicrobial therapeutics. Elucidating and utilising the modulatory properties of cathelicidins has the potential to inform the development of synthetic peptide analogues and novel therapeutic approaches based on enhancing innate host defence against infection with or without direct microbicidal targeting of pathogens.

Understanding augmented reality concepts and applications

CERN Document Server

Craig, Alan B

2013-01-01

Augmented reality is not a technology. Augmented reality is a medium. Likewise, a book on augmented reality that only addresses the technology that is required to support the medium of augmented reality falls far short of providing the background that is needed to produce, or critically consume augmented reality applications. One reads a book. One watches a movie. One experiences augmented reality. Understanding Augmented Reality addresses the elements that are required to create compelling augmented reality experiences. The technology that supports

Updates in weight loss surgery and gastrointestinal peptides

DEFF Research Database (Denmark)

Svane, Maria Saur; Bojsen-Møller, Kirstine N; Madsbad, Sten

2015-01-01

PURPOSE OF REVIEW: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy are referred to as 'metabolic surgery' due to hormonal shifts with impacts on diabetes remission and weight loss. The purpose of this review is to summarize recent findings in mechanisms underlying beneficial effects...... of weight loss surgery. RECENT FINDINGS: Importantly, gut hormone secretion is altered after RYGB and sleeve gastrectomy due to accelerated transit of nutrients to distal parts of the small intestine, leading to excessive release of L-cell peptide hormones [e.g. glucagon-like peptide-1 (GLP-1), peptide YY......; as demonstrated by relapse of impaired glucose tolerance in studies blocking the GLP-1 receptor by exendin 9-39, and later after major weight loss increased peripheral insulin sensitivity. Gut hormone secretion changes towards a more anorectic profile and is likely important for less caloric intake and weight...

Substance P release from rat hypothalamus and spinal cord

International Nuclear Information System (INIS)

Kronheim, S.; Sheppard, M.C.; Pimstone, B.L.

1980-01-01

A specific and sensitive radioimmunoassay for substance P has been developed to study the release of immunoreactive substance P from incubated rat hypothalamus and rat spinal cord in vitro. Release was significantly increased in the presence of two depolarizing stimuli (56 mM KCl and 75 μM veratrine) and was calcium-dependent. The released immunoreactive material diluted in parallel with synthetic substance P and showed close identity on Sephadex chromatography. A neuromodulator role for the peptide in the central nervous system is suggested

Growth hormone-releasing peptide-biotin conjugate stimulates myocytes differentiation through insulin-like growth factor-1 and collagen type I.

Science.gov (United States)

Lim, Chae Jin; Jeon, Jung Eun; Jeong, Se Kyoo; Yoon, Seok Jeong; Kwon, Seon Deok; Lim, Jina; Park, Keedon; Kim, Dae Yong; Ahn, Jeong Keun; Kim, Bong-Woo

2015-09-01

Based on the potential beneficial effects of growth hormone releasing peptide (GHRP)-6 on muscle functions, a newly synthesized GHRP-6-biotin conjugate was tested on cultured myoblast cells. Increased expression of myogenic marker proteins was observed in GHRP-6-biotin conjugate-treated cells. Additionally, increased expression levels of insulin-like growth factor-1 and collagen type I were observed. Furthermore, GHRP-6-biotin conjugate-treated cells showed increased metabolic activity, as indicated by increased concentrations of energy metabolites, such as ATP and lactate, and increased enzymatic activity of lactate dehydrogenase and creatine kinase. Finally, binding protein analysis suggested few candidate proteins, including desmin, actin, and zinc finger protein 691 as potential targets for GHRP6-biotin conjugate action. These results suggest that the newly synthesized GHRP-6-biotin conjugate has myogenic stimulating activity through, at least in part, by stimulating collagen type I synthesis and several key proteins. Practical applications of the GHRP-6-biotin conjugate could include improving muscle condition.

Modeling the Effects of Augmentation Strategies on the Control of Dengue Fever With an Impulsive Differential Equation.

Science.gov (United States)

Zhang, Xianghong; Tang, Sanyi; Cheke, Robert A; Zhu, Huaiping

2016-10-01

Dengue fever has rapidly become the world's most common vector-borne viral disease. Use of endosymbiotic Wolbachia is an innovative technology to prevent vector mosquitoes from reproducing and so break the cycle of dengue transmission. However, strategies such as population eradication and replacement will only succeed if appropriate augmentations with Wolbachia-infected mosquitoes that take account of a variety of factors are carried out. Here, we describe the spread of Wolbachia in mosquito populations using an impulsive differential system with four state variables, incorporating the effects of cytoplasmic incompatibility and the augmentation of Wolbachia-infected mosquitoes with different sex ratios. We then evaluated (a) how each parameter value contributes to the success of population replacement; (b) how different release quantities of infected mosquitoes with different sex ratios affect the success of population suppression or replacement; and (c) how the success of these two strategies can be realized to block the transmission of dengue fever. Analysis of the system's stability, bifurcations and sensitivity reveals the existence of forward and backward bifurcations, multiple attractors and the contribution of each parameter to the success of the strategies. The results indicate that the initial density of mosquitoes, the quantities of mosquitoes released in augmentations and their sex ratios have impacts on whether or not the strategies of population suppression or replacement can be achieved. Therefore, successful strategies rely on selecting suitable strains of Wolbachia and carefully designing the mosquito augmentation program.

Prediction of Impending Type 1 Diabetes through Automated Dual-Label Measurement of Proinsulin:C-Peptide Ratio.

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Annelien Van Dalem

Full Text Available The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C. The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA, and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release.Between-day imprecision (n = 20 and split-sample analysis (n = 95 were used to compare TT-TRFIA (AutoDelfia, Perkin-Elmer with separate methods for proinsulin (in-house TRFIA and C-peptide (Elecsys, Roche. High-risk multiple autoantibody-positive first-degree relatives (n = 49; age 5-39 were tested for fasting PI:C, HOMA2-IR and hyperglycemic clamp and followed for 20-57 months (interquartile range.TT-TRFIA values for proinsulin, C-peptide and PI:C correlated significantly (r2 = 0.96-0.99; P<0.001 with results obtained with separate methods. TT-TRFIA achieved better between-day %CV for PI:C at three different levels (4.5-7.1 vs 6.7-9.5 for separate methods. In high-risk relatives fasting PI:C was significantly and inversely correlated (rs = -0.596; P<0.001 with first-phase C-peptide release during clamp (also with second phase release, only available for age 12-39 years; n = 31, but only after normalization for HOMA2-IR. In ROC- and Cox regression analysis, HOMA2-IR-corrected PI:C predicted 2-year progression to diabetes equally well as clamp-derived C-peptide release.The reproducibility of PI:C benefits from the automated simultaneous determination of both hormones. HOMA2-IR-corrected PI:C may serve as a minimally invasive alternative to the more tedious hyperglycemic clamp test.

The Role Of Milk Peptide As Antimicrobial Agent In Supporting Health Status

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Eni Kusumaningtyas

2013-06-01

Full Text Available Antimicrobial peptide is commonly present in all species as a component of their innate immune defense against infection. Antimicrobial peptides derived from milk such as isracidin, casocidin, casecidin and other fragments with variety of amino acid sequence are released upon enzymatic hydrolysis from milk protein К-casein, α-casein, β-casein, α-lactalbumin and β- lactoglobulin. These peptides were produced by the activity of digestive or microbial protease such as trypsin, pepsin, chymosin or alcalase. The mode of action of these peptides is by interaction of their positive with negative charge of target cell membrane leading to disruption of membrane associated with physiological event such as cell division or translocation of peptide across the membrane to interact with cytoplasmic target. Modification of charged or nonpolar aliphatic residues within peptides can enhance or reduce the activities of the peptides against a number of microbial strains and it seems to be strain dependent. Several peptides act not only as an antimicrobial but also as an angiotensin-converting enzyme inhibitor, antioxidant, immunomodulator, antiinflamation, food and feed preservative. Although the commercial production of these peptides is still limited due to lack of suitable large-scale technologies, fast development of some methods for peptide production will hopefully increase the possibility for mass production.

Neurotensin releases norepinephrine differentially from perfused hypothalamus of sated and fasted rat

International Nuclear Information System (INIS)

Lee, T.F.; Rezvani, A.H.; Hepler, J.R.; Myers, R.D.

1987-01-01

The central injection of neurotensin (NT) has been reported to attenuate the intake of food in the fasted animal. To determine whether endogenous norepinephrine (NE) is involved in the satiating effect of NT, the in vivo activity of NE in circumscribed sites in the hypothalamus of the unanesthetized rat was examined. Bilateral guide tubes for push-pull perfusion were implanted stereotaxically to rest permanently above one of several intended sites of perfusion, which included the paraventricular nucleus (PVN), ventromedial nucleus (VMN), and the lateral hypothalamic (LH) area. After endogenous stores of NE at a specific hypothalamic locus were radiolabeled by microinjection of 0.02-0.5 μCi of [ 3 H]NE, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 μl/min over successive intervals of 5.0 min. When 0.05 or 0.1 μg/μl NT was added to the perfusate, the peptide served either to enhance or educe the local release of NE at 50% of the sites of perfusion. In these experiments, the circumscribed effect of NT on the characteristics of catecholamine efflux depended entirely on the state of hunger or satiety of the rat. That is, when NT was perfused in the fully satiated rat, NE release was augmented within the PVn or VMN; conversely, NE release was inhibited in the LH. in the animal fasted for 18-22 h, NT exerted an opposite effect on the activity of NE within the same anatomical loci in that the efflux of NE was enhanced in the LH but attenuated or unaffected in the PVN or VMN. Taken together, these observations provide experimental support for the view-point that NT could act as a neuromodulator of the activity of hypothalamic noradrenergic neurons that are thought to play a functional role in the regulation of food intake

An in vitro study of peptide-loaded alginate nanospheres for antagonizing the inhibitory effect of Nogo-A protein on axonal growth

International Nuclear Information System (INIS)

Zhai, Peng; Chen, X B; Schreyer, David J

2015-01-01

The adult mammalian central nervous system has limited ability to regenerate after injury. This is due, in part, to the presence of myelin-associated axon growth inhibitory proteins such as Nogo-A that bind and activate the Nogo receptor, leading to profound inhibition of actin-based motility within the growing axon tip. This paper presents an in vitro study of the use of a Nogo receptor-blocking peptide to antagonize the inhibitory effect of Nogo-A on axon growth. Alginate nanospheres were fabricated using an emulsion technique and loaded with Nogo receptor-blocking peptide, or with other model proteins. Protein release profiles were studied, and retention of the bioactivity of released proteins was verified. Primary dorsal root ganglion neurons were cultured and their ability to grow neurites was challenged with Nogo-A chimeric protein in the absence or presence of Nogo receptor antagonist peptide-loaded alginate nanospheres. Our results demonstrate that peptide released from alginate nanospheres could overcome the growth inhibitory effect of Nogo-A, suggesting that a similar peptide delivery strategy using alginate nanospheres might be used to improve axon regeneration within the injured central nervous system. (paper)

Review: evolution of GnIH and related peptides structure and function in the chordates.

Science.gov (United States)

Osugi, Tomohiro; Ubuka, Takayoshi; Tsutsui, Kazuyoshi

2014-01-01

Discovery of gonadotropin-inhibitory hormone (GnIH) in the Japanese quail in 2000 was the first to demonstrate the existence of a hypothalamic neuropeptide inhibiting gonadotropin release. We now know that GnIH regulates reproduction by inhibiting gonadotropin synthesis and release via action on the gonadotropin-releasing hormone (GnRH) system and the gonadotrope in various vertebrates. GnIH peptides identified in birds and mammals have a common LPXRF-amide (X = L or Q) motif at the C-terminus and inhibit pituitary gonadotropin secretion. However, the function and structure of GnIH peptides are diverse in fish. Goldfish GnIHs possessing a C-terminal LPXRF-amide motif have both stimulatory and inhibitory effects on gonadotropin synthesis or release. The C-terminal sequence of grass puffer and medaka GnIHs are MPQRF-amide. To investigate the evolutionary origin of GnIH and its ancestral structure and function, we searched for GnIH in agnathans, the most ancient lineage of vertebrates. We identified GnIH precursor gene and mature GnIH peptides with C-terminal QPQRF-amide or RPQRF-amide from the brain of sea lamprey. Lamprey GnIH fibers were in close proximity to GnRH-III neurons. Further, one of lamprey GnIHs stimulated the expression of lamprey GnRH-III peptide in the hypothalamus and gonadotropic hormone β mRNA expression in the pituitary. We further identified the ancestral form of GnIH, which had a C-terminal RPQRF-amide, and its receptors in amphioxus, the most basal chordate species. The amphioxus GnIH inhibited cAMP signaling in vitro. In sum, the original forms of GnIH may date back to the time of the emergence of early chordates. GnIH peptides may have had various C-terminal structures slightly different from LPXRF-amide in basal chordates, which had stimulatory and/or inhibitory functions on reproduction. The C-terminal LPXRF-amide structure and its inhibitory function on reproduction may be selected in later-evolved vertebrates, such as birds and mammals.

Impact of exogenous hyperglucagonemia on postprandial concentrations of gastric inhibitory polypeptide and glucagon-like peptide-1 in humans

DEFF Research Database (Denmark)

Meier, Juris J; Ritter, Peter R; Jacob, Alexandra

2010-01-01

Postprandial secretion of glucagon-like peptide 1 (GLP-1) has been found diminished in some patients with type 2 diabetes mellitus (T2DM) and high glucagon concentrations. We examined the effects of exogenous glucagon on the release of incretin hormones.......Postprandial secretion of glucagon-like peptide 1 (GLP-1) has been found diminished in some patients with type 2 diabetes mellitus (T2DM) and high glucagon concentrations. We examined the effects of exogenous glucagon on the release of incretin hormones....

Jointly Optimize Data Augmentation and Network Training: Adversarial Data Augmentation in Human Pose Estimation

OpenAIRE

Peng, Xi; Tang, Zhiqiang; Yang, Fei; Feris, Rogerio; Metaxas, Dimitris

2018-01-01

Random data augmentation is a critical technique to avoid overfitting in training deep neural network models. However, data augmentation and network training are usually treated as two isolated processes, limiting the effectiveness of network training. Why not jointly optimize the two? We propose adversarial data augmentation to address this limitation. The main idea is to design an augmentation network (generator) that competes against a target network (discriminator) by generating `hard' au...

Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target

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Rafael eRoesler

2012-12-01

Full Text Available Neuropeptides acting on specific cell membrane receptors of the G protein-coupled receptor (GPCR superfamily regulate a range of important aspects of nervous and neuroendocrine function. Gastrin-releasing peptide (GRP is a mammalian neuropeptide that binds to the GRP receptor (GRPR, BB2. Increasing evidence indicates that GRPR-mediated signaling in the central nervous system (CNS plays an important role in regulating brain function, including aspects related to emotional responses, social interaction, memory, and feeding behavior. In addition, some alterations in GRP or GRPR expression or function have been described in patients with neurodegenerative, neurodevelopmental, and psychiatric disorders, as well as in brain tumors. Findings from preclinical models are consistent with the view that the GRPR might play a role in brain disorders, and raise the possibility that GRPR agonists might ameliorate cognitive and social deficits associated with neurological diseases, while antagonists may reduce anxiety and inhibit the growth of some types of brain cancer. Further preclinical and translational studies evaluating the potential therapeutic effects of GRPR ligands are warranted.

Confronting an augmented reality

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John Hedberg

2012-08-01

Full Text Available How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself? In this article, we seek to initiate a discussion that focuses on these questions, and suggest that they be used as drivers for research into effective educational applications of augmented reality. We discuss how multi-modal, sensorial augmentation of reality links to existing theories of education and learning, focusing on ideas of cognitive dissonance and the confrontation of new realities implied by exposure to new and varied perspectives. We also discuss connections with broader debates brought on by the social and cultural changes wrought by the increased digitalisation of our lives, especially the concept of the extended mind. Rather than offer a prescription for augmentation, our intention is to throw open debate and to provoke deep thinking about what interacting with and creating an augmented reality might mean for both teacher and learner.

Penetration of polymeric nanoparticles loaded with an HIV-1 inhibitor peptide derived from GB virus C in a vaginal mucosa model.

Science.gov (United States)

Ariza-Sáenz, Martha; Espina, Marta; Bolaños, Nuria; Calpena, Ana Cristina; Gomara, María José; Haro, Isabel; García, María Luisa

2017-11-01

Despite the great effort to decrease the HIV infectivity rate, current antiretroviral therapy has several weaknesses; poor bioavailability, development of drug resistance and poor ability to access tissues. However, molecules such as peptides have emerged asa new expectative to HIV eradication. The vaginal mucosa is the main spreading point of HIV. There are natural barriers such as the vaginal fluid which protects the vaginal epithelium from any foreign agents reaching it. This work has developed and characterized Nanoparticles (NPs) coated with glycol chitosan (GC), loaded with an HIV-1 inhibitor peptide (E2). In vitro release and ex vivo studies were carried out using the vaginal mucosa of swine and the peptide was determined by HPLC MS/MS validated method. Moreover, the peptide was labeled with 5(6)-carboxyfluoresceine and entrapped into the NPs to carried out in vivo studies and to evaluate the NPs penetration and toxicity in the vaginal mucosa of the swine. The mean size of the NPs, ξ and the loading percentage were fundamental features for to reach the vaginal tissue and to release the peptide within intercellular space. The obtained results suggesting that the fusion inhibitor peptides loaded into the NPs coated with GC might be a new way to fight the HIV-1, due to the formulation might reach the human epithelial mucosa and release peptide without any side effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Secretion of [Met]enkephalyl-Arg6-Phe7-related peptides and catecholamines from bovine adrenal chromaffin cells: modification by changes in cyclic AMP and by treatment with reserpine.

Science.gov (United States)

Adams, M; Boarder, M R

1987-07-01

Investigations into the effects of culturing bovine adrenal chromaffin cells in the presence (72 h) of dibutyryl cyclic AMP, forskolin, and reserpine on the level and release of [Met]enkephalyl-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline are reported. The assay for [Met]enkephalyl-Arg6-Phe7 immunoreactivity recognises both peptide B, the 31-amino acid carboxy-terminal segment of proenkephalin, and its heptapeptide fragment, [Met]enkephalyl-Arg6-Phe7. Treatments that elevate cyclic AMP increase the amount of peptide immunoreactivity in these cells; this is predominantly peptide B-like immunoreactivity in both control cells and cyclic AMP-elevated cells. Treatment with reserpine gives no change in total immunoreactivity levels, but does not result in increased accumulation of the heptapeptide [Met]enkephalyl-Arg6-Phe7 at the expense of immunoreactivity that elutes with its immediate precursor, peptide B. Cyclic AMP treatment causes either no change or a decrease in levels of accumulated noradrenaline and adrenaline. However, the release of [Met]enkephalin-Arg6-Phe7 immunoreactivity, noradrenaline, and adrenaline is increased by 72-h pretreatment with forskolin or dibutyryl cyclic AMP, whether release is stimulated by nicotine or elevated potassium. In each case the molecular form of [Met]enkephalyl-Arg6-Phe7 immunoreactivity that is released approximately reflects the cell content. Pretreatment with reserpine has no effect on the total [Met]enkephalyl-Arg6-Phe7 immunoreactivity released, but does result in an increased release of the heptapeptide and a decrease in release of peptide B-like immunoreactivity. The studies suggest that the levels of [Met]enkephalyl-Arg6-Phe7 and peptide B available for release are controlled both at the level of proenkephalin synthesis and at the level of double-basic residue proteolysis.

Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease

DEFF Research Database (Denmark)

Weiner, H L; Lemere, C A; Maron, R

2000-01-01

Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated ......Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease...... cerebral Abeta deposition, suggesting a novel mucosal immunological approach for the treatment and prevention of AD....

Toxicity of Biologically Active Peptides and Future Safety Aspects: An Update.

Science.gov (United States)

Khan, Fazlullah; Niaz, Kamal; Abdollahi, Mohammad

2018-02-18

Peptides are fragments of proteins with significant biological activities. These peptides are encoded in the protein sequence. Initially, such peptides are inactive in their parental form, unless proteolytic enzymes are released. These peptides then exhibit various functions and play a therapeutic role in the body. Besides the therapeutic and physiological activities of peptides, the main purpose of this study was to highlight the safety aspects of peptides. We performed an organized search of available literature using PubMed, Google Scholar, Medline, EMBASE, Reaxys and Scopus databases. All the relevant citations including research and review articles about the toxicity of biologically active peptides were evaluated and gathered in this study. Biological peptides are widely used in the daily routine ranging from food production to the cosmetics industry and also they have a beneficial role in the treatment and prevention of different diseases. These peptides are manufactured by both chemical and biotechnological techniques, which show negligible toxicity, however, some naturally occurring peptides and enzymes may induce high toxicity. Depending upon the demand and expected use in the food or pharmaceutical industry, we need different approaches to acertain the safety of these peptides preferentially through in silico methods. Intestinal wall disruption, erythrocytes and lymphocytes toxicity, free radical production, enzymopathic and immunopathic tissue damage and cytotoxicity due to the consumption of peptides are the main problems in the biological system that lead to various complicated disorders. Therefore, before considering biologically active peptides for food production and for therapeutic purpose, it is first necessary to evaluate the immunogenicity and toxicities of peptides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Activity of Genital Tract Secretions and Synthetic Antimicrobial Peptides against Group B Streptococcus.

Science.gov (United States)

Agarwal, Nidhi; Buckley, Niall; Nakra, Natasha; Gialanella, Philip; Yuan, Weirong; Ghartey, Jeny P

2015-12-01

Genital tract secretions inhibit Escherichia coli (E. coli) through antimicrobial peptides (AMP) secreted by the host and vaginal microbiota. However, there are limited data against group B Streptococcus (GBS). Group B Streptococcus were incubated with cervico-vaginal lavage (CVL) samples from healthy non-pregnant women (n = 12) or synthetic AMP and monitored for bacterial growth using a turbidimetric approach. E. coli inhibitory activity was determined by a colony-forming unit assay. None of the CVL samples inhibited GBS. The human neutrophil peptide-1 and human defensin 5 inhibited GBS growth by ≥80% at concentrations ≥20 μg/mL and ≥50 μg/mL, respectively, while human beta-defensin 2 and LL-37 did not inhibit at highest concentration tested (100 μg/mL). In contrast, all AMP inhibited E. coli. Antimicrobial peptides may protect against E. coli colonization but have more limited activity against GBS. Future studies will focus on augmenting host defense with specific AMP to prevent genitourinary infection with these pathogenic organisms. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biological evaluation of 177Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting

International Nuclear Information System (INIS)

Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

2015-01-01

Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO 3 H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH 2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with 177 Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10 6 cells. The radio-peptide slowly internalized, and 24.4 ± 0.5% of the total binding was internalized in 4 hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02 ± 9.36 at 1.5 hr p.i., and was increased to 216.33 ± 61.58 at 24 hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this 177 Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors

A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers.

Science.gov (United States)

Raza, Faisal; Zafar, Hajra; Zhu, Ying; Ren, Yuan; -Ullah, Aftab; Khan, Asif Ullah; He, Xinyi; Han, Han; Aquib, Md; Boakye-Yiadom, Kofi Oti; Ge, Liang

2018-01-18

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today's world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, "release mechanisms" their physical and chemical characteristics and diverse applications.

Release of PYY from pig intestinal mucosa; luminal and neural regulation

DEFF Research Database (Denmark)

Sheikh, S P; Holst, J J; Orskov, C

1989-01-01

in release of PYY into the circulation. Stimulation of the splanchnic nerves did not affect the basal release of PYY. PYY-immunoreactivity extracted from ileal tissue or released to plasma or perfusate from the ileum was indistinguishable from synthetic porcine PYY by gel filtration and reverse phase HPLC...... of PYY was observed in isolated perfused pig ileum in response to luminal stimulation with glucose and vascular administration of the neuropeptide gastrin-releasing peptide (GRP). Electrical stimulation of the vagus nerve supply to the distal small intestine in intact anaesthetized pigs resulted...

Annexin 1 and Melanocortin Peptide Therapy for Protection Against Ischaemic-Reperfusion Damage in the Heart

Directory of Open Access Journals (Sweden)

F.N.E. Gavins

2006-01-01

Full Text Available Cardiovascular disease is a major cause of mortality within the western world affecting 2.7 million British people. This review highlights the beneficial effects of naturally occurring hormones and their peptides, in myocardial ischaemic-injury (MI models, a disease pathology in which cytokines and neutrophils play a causal role. Here we discuss two distinct classes of endogenous peptides: the steroid inducible annexin 1 and the melanocortin peptides. Annexin 1 and the melanocortins counteract the most important part of the host inflammatory response, namely, the process of leukocyte extravasation, as well as release of proinflammatory mediators. Their biological effects are mediated via the seven transmembrane G-protein-coupled receptors, the fMLP receptor family (or FPR, and the melanocortin receptors, respectively. Pharmacological analysis has demonstrated that the first 24 amino acids of the N-terminus (termed Ac2-26 are the most active region. Both exogenous annexin 1 and its peptides demonstrate cardioprotectiveness and continuing work is required to understand this annexin 1/FPR relationship fully. The melanocortin peptides are derived from a precursor molecule called the POMC protein. These peptides display potent anti-inflammatory effects in human and animal models of disease. In MI, the MC3R has been demonstrated to play an important role in mediating the protective effects of these peptides. The potential anti-inflammatory role for endogenous peptides in cardiac disease is in its infancy. The inhibition of cell migration and release of cytokines and other soluble mediators appears to play an important role in affording protection in ischaemic injury and thus may lead to potential therapeutic targets.

The use of thiolated polymers as carrier matrix in oral peptide delivery--proof of concept.

Science.gov (United States)

Bernkop-Schnürch, Andreas; Pinter, Yvonne; Guggi, Davide; Kahlbacher, Hermann; Schöffmann, Gudrun; Schuh, Maximilian; Schmerold, Ivo; Del Curto, Maria Dorly; D'Antonio, Mauro; Esposito, Pierandrea; Huck, Christian

2005-08-18

It was the aim of this study to develop an oral delivery system for the peptide drug antide. The stability of the therapeutic peptide towards gastrointestinal peptidases was evaluated. The therapeutic agent and the permeation mediator glutathione were embedded in the thiolated polymer chitosan-4-thio-butylamidine conjugate (chitosan-TBA conjugate) and compressed to tablets. Drug release studies were performed in the dissolution test apparatus according to the Pharmacopoeia Europea using the paddle method and demineralized water as release medium. In order to avoid mucoadhesion of these delivery systems already in the oral cavity and oesophagus tablets were coated with a triglyceride. These tablets were orally given to pigs (weight: 50+/-2 kg; Edelschwein Pietrain). Moreover, antide was administered intravenously, subcutaneously and orally in solution. Results showed stability of antide towards pepsin, trypsin and chymotrypsin. In contrast, antide was rapidly degraded by elastase. Consequently a stomach-targeted delivery system was designed. Drug release studies demonstrated an almost zero-order controlled release of antide over 8 h. In vivo studies demonstrated a relative bioavailability of 34.4% for the subcutaneous administration. Oral administration of antide in solution led to no detectable concentrations of the drug in plasma at all. In contrast, administering antide being incorporated in the thiolated polymer resulted in a significant uptake of the peptide. The absolute and relative bioavailability was determined to be 1.1% and 3.2%, respectively.

Involvement of arachidonate metabolism in neurotensin-induced prolactin release in vitro

International Nuclear Information System (INIS)

Canonico, P.L.; Speciale, C.; Sortino, M.A.; Scapagnini, U.

1985-01-01

Neurotensin increased in a concentration-dependent manner the level of hypophyseal [ 3 H]arachidonic acid in vitro as well as prolactin release from hemipituitary glands. The effect of 1 microM neurotensin on arachidonate release was already present at 2.5 min, maximal at 5, and disappeared after a 10-min incubation. Neurotensin analogues produced an enhancement of hypophyseal arachidonate similar to their relative potencies in other cellular systems, whereas other peptides (somatostatin and vasoactive intestinal peptide) were devoid of any effect on the concentration of the fatty acid in the pituitary. Seventy micromoles RHC 80267, a rather selective inhibitor of diacylglycerol lipase, completely prevented the neurotensin-stimulated prolactin release and decreased arachidonate release both in basal or in neurotensin-induced conditions. Similar results were obtained with 50 microM quinacrine, a phospholipase A2 inhibitor. To clarify whether arachidonate released by neurotensin requires a further metabolism through specific pathways to stimulate prolactin release, the authors used indomethacin and BW 755c, two blockers of cyclooxygenase and lipoxygenase pathways. Thirty micromoles indomethacin, a dose active to inhibit cyclooxygenase, did not affect unesterified arachidonate levels either in basal or in neurotensin-induced conditions; moreover, the drug did not modify basal prolactin release but slightly potentiated the stimulatory effect of neurotensin on the release of the hormone. On the other hand, 250 microM BW 755c, an inhibitor of both cyclooxygenase and lipoxygenase pathways, significantly inhibited both basal and neurotensin-stimulated prolactin release and further potentiated the increase of the fatty acid concentrations produced by 1 microM neurotensin

The role of brain peptides in the reproduction of blue gourami males (Trichogaster trichopterus).

Science.gov (United States)

Levy, Gal; Degani, Gad

2013-10-01

In all vertebrates, reproduction and growth are closely linked and both are controlled by complex hormonal interactions at the brain-pituitary level. In this study, we focused on the reciprocal interactions between brain peptides that regulate growth and reproductive functions in a teleostei fish (blue gourami Trichogaster trichopterus). An increase in gonadotropin-releasing hormone 1 (GnRH1) gene expression was detected during ontogeny, and this peptide increased growth hormone (GH) and β follicle-stimulating hormone (βFSH) gene expression in pituitary cell culture. However, although no change in gonadotropin-releasing hormone 2 (GnRH2) gene expression during the reproductive cycle or sexual behavior was detected, a stimulatory effect of this peptide on β gonadotropins (βGtH) gene expression was observed. In addition, pituitary adenylate cyclase-activating polypeptide 38 (PACAP-38) inhibited GnRH-analog-induced βFSH gene expression, and co-treatment of cells with GnRH-analog and PACAP-38 inhibited GnRH-analog-stimulatory and PACAP-38-inhibitory effects on GH gene expression. These findings together with previous studies were used to create a model summarizing the mechanism of brain peptides (GnRH, PACAP and its related peptide) and the relationship to reproduction and growth through pituitary hormone gene expression during ontogenesis and reproductive stages in blue gourami. © 2013 Wiley Periodicals, Inc.

Biological control of fruit flies (Diptera: Tephritidae) through parasitoid augmentative releases: Current status

International Nuclear Information System (INIS)

Montoya, Pablo; Liedo, Pablo

2000-01-01

Fruit flies are among the main pests affecting the world fruit industry (Aluja 1993). Bait sprays have traditionally been used successfully to control them; however, the side effects on the environment and health hazards commonly associated with pesticides, have resulted in strong public opposition to the use of bait sprays. This is particularly so when sprays are applied in urban areas or in coffee plantations where, although Medflies are present, they do not pose a danger to crops. Alternative methods that are effective and environmental friendly to suppress fruit fly populations are highly desirable. Biological control, the use of natural enemies to suppress pest populations, represents such an alternative. Some of the most successful cases of biological control are the control of Iceria purchasi Maskell (Homoptera: Margarodidae) by Rodolia cardinalis Mulsant (Coleoptera: Coccinellidae) in California (De Bach 1968, van den Bosch et al. 1982), and the control of Aleurocanthus woglumi Ashby (Homoptera: Aleyrodidae) mainly by Encarsia (=Prospaltella) opulenta Silv. (Hymenoptera: Aphelinidae) in Mexico (Jimenez 1961, 1971), both using the classical approach. However, this approach has been limited to certain conditions of environmental stability and biodiversity which are only found in a few ecosystems. Other factors, such as types of pests, the economic threshold and product quality requirements represent additional limitations. The best option in many cases could be augmentative biological control, which could overcome some of the deficiencies of the classical approach (Sivinski 1996). According to Knipling (1992) and Barclay (1987), augmentative biological control can be considered as a formal alternative for suppressing pest populations and even for use in eradication programmes, after integration with the sterile insect technique (SIT). In this approach, mass production of natural enemies is required and this production has to be cost effective

Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by “Silencing” Central Glucagon-Like Peptide 1 Signaling in Rats

OpenAIRE

Maniscalco, James W.; Zheng, Huiyuan; Gordon, Patrick J.; Rinaman, Linda

2015-01-01

Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stre...

Atrial natriuretic peptide down-regulates LPS/ATP-mediated IL-1β release by inhibiting NF-kB, NLRP3 inflammasome and caspase-1 activation in THP-1 cells.

Science.gov (United States)

Mezzasoma, Letizia; Antognelli, Cinzia; Talesa, Vincenzo Nicola

2016-02-01

Atrial natriuretic peptide (ANP) is an hormone/paracrine/autocrine factor regulating cardiovascular homeostasis by guanylyl cyclase natriuretic peptide receptor (NPR-1). ANP plays an important role also in regulating inflammatory and immune systems by altering macrophages functions and cytokines secretion. Interleukin-1β (IL-1β) is a potent pro-inflammatory cytokine involved in a wide range of biological responses, including the immunological one. Unlike other cytokines, IL-1β production is rigorously controlled. Primarily, NF-kB activation is required to produce pro-IL-1β; subsequently, NALP3 inflammasome/caspase-1 activation is required to cleave pro-IL-1β into the active secreted protein. NALP3 is a molecular platform capable of sensing a large variety of signals and a major player in innate immune defense. Due to their pleiotropism, IL-1β and NALP3 dysregulation is a common feature of a wide range of diseases. Therefore, identifying molecules regulating IL-1β/NALP3/caspase-1 expression is an important step in the development of new potential therapeutic agents. The aim of our study was to evaluate the effect of ANP on IL-1β/NALP3/caspase-1 expression in LPS/ATP-stimulated human THP1 monocytes. We provided new evidence of the direct involvement of ANP/NPR-1/cGMP axis on NF-kB/NALP3/caspase-1-mediated IL-1β release and NF-kB-mediated pro-IL-1β production. In particular, ANP inhibited both NF-kB and NALP3/caspase-1 activation leading to pro- and mature IL-1β down-regulation. Our data, pointing out a modulatory role of this endogenous peptide on IL-1β release and on NF-kB/NALP3/caspase-1 activation, indicate an important anti-inflammatory and immunomodulatory effect of ANP via these mechanisms. We suggest a possible employment of ANP for the treatment of inflammatory/immune-related diseases and IL-1β/NALP3-associated disorders, affecting millions of people worldwide.

Mobile Augmented Reality Applications

OpenAIRE

Prochazka, David; Stencl, Michael; Popelka, Ondrej; Stastny, Jiri

2011-01-01

Augmented reality have undergone considerable improvement in past years. Many special techniques and hardware devices were developed, but the crucial breakthrough came with the spread of intelligent mobile phones. This enabled mass spread of augmented reality applications. However mobile devices have limited hardware capabilities, which narrows down the methods usable for scene analysis. In this article we propose an augmented reality application which is using cloud computing to enable using...

Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes

DEFF Research Database (Denmark)

Herman, Gary A; Bergman, Arthur; Stevens, Catherine

2006-01-01

CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral antihyperglyce......CONTEXT: In response to a meal, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and modulate glycemic control. Normally these incretins are rapidly degraded by dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors are a novel class of oral...... antihyperglycemic agents in development for the treatment of type 2 diabetes. The degree of DPP-4 inhibition and the level of active incretin augmentation required for glucose lowering efficacy after an oral glucose tolerance test (OGTT) were evaluated. OBJECTIVE: The objective of the study was to examine...... concentrations; and sitagliptin pharmacokinetics. RESULTS: Sitagliptin dose-dependently inhibited plasma DPP-4 activity over 24 h, enhanced active GLP-1 and GIP levels, increased insulin/C-peptide, decreased glucagon, and reduced glycemic excursion after OGTTs administered at 2 and 24 h after single oral 25...

CAR T Cells Releasing IL-18 Convert to T-Bethigh FoxO1low Effectors that Exhibit Augmented Activity against Advanced Solid Tumors

Directory of Open Access Journals (Sweden)

Markus Chmielewski

2017-12-01

Full Text Available Adoptive therapy with chimeric antigen receptor (CAR-redirected T cells has achieved remarkable efficacy in the treatment of hematopoietic malignancies. However, eradicating large solid tumors in advanced stages of the disease remains challenging. We explored augmentation of the anti-tumor immune reaction by establishing an acute inflammatory reaction. Systematic screening indicates that IL-18 polarizes CAR T cells toward T-bethigh FoxO1low effectors with an acute inflammatory response. CAR T cells engineered with inducible IL-18 release exhibited superior activity against large pancreatic and lung tumors that were refractory to CAR T cells without cytokines. IL-18 CAR T cell treatment was accompanied by an overall change in the immune cell landscape associated with the tumor. More specifically, CD206− M1 macrophages and NKG2D+ NK cells increased in number, whereas Tregs, suppressive CD103+ DCs, and M2 macrophages decreased, suggesting that “iIL18 TRUCKs” can be used to sensitize large solid tumor lesions for successful immune destruction.

Cell-Penetrating Ability of Peptide Hormones: Key Role of Glycosaminoglycans Clustering

Directory of Open Access Journals (Sweden)

Armelle Tchoumi Neree

2015-11-01

Full Text Available Over the last two decades, the potential usage of cell-penetrating peptides (CPPs for the intracellular delivery of various molecules has prompted the identification of novel peptidic identities. However, cytotoxic effects and unpredicted immunological responses have often limited the use of various CPP sequences in the clinic. To overcome these issues, the usage of endogenous peptides appears as an appropriate alternative approach. The hormone pituitary adenylate-cyclase-activating polypeptide (PACAP38 has been recently identified as a novel and very efficient CPP. This 38-residue polycationic peptide is a member of the secretin/glucagon/growth hormone-releasing hormone (GHRH superfamily, with which PACAP38 shares high structural and conformational homologies. In this study, we evaluated the cell-penetrating ability of cationic peptide hormones in the context of the expression of cell surface glycosaminoglycans (GAGs. Our results indicated that among all peptides evaluated, PACAP38 was unique for its potent efficiency of cellular uptake. Interestingly, the abilities of the peptides to reach the intracellular space did not correlate with their binding affinities to sulfated GAGs, but rather to their capacity to clustered heparin in vitro. This study demonstrates that the uptake efficiency of a given cationic CPP does not necessarily correlate with its affinity to sulfated GAGs and that its ability to cluster GAGs should be considered for the identification of novel peptidic sequences with potent cellular penetrating properties.

Augmenting Clozapine With Sertindole

DEFF Research Database (Denmark)

Nielsen, Jimmi; Emborg, Charlotte; Gydesen, Susanne

2012-01-01

Clozapine augmentation with antipsychotic drugs is widely used despite sparse evidence supporting this strategy. Sertindole is a nonsedating atypical antipsychotic drug with low affinity for cholinergic receptors, which makes it potentially suitable for augmentation of clozapine. The study design...... glucose, lipids, and electrocardiogram. Clozapine augmentation with sertindole was not superior to placebo regarding total score or subscale score of the Positive and Negative Syndrome Scale, Clinical Global Impression, World Health Organization Quality of Life Brief, or Drug Attitude Inventory....... No increased adverse effects compared with placebo were found. Four patients randomized to sertindole experienced a significant worsening of psychosis, and 2 of them required psychiatric admission. Metabolic parameters were unchanged during the study, but augmentation of clozapine with sertindole...

[Augmentation technique on the proximal humerus].

Science.gov (United States)

Scola, A; Gebhard, F; Röderer, G

2015-09-01

The treatment of osteoporotic fractures is still a challenge. The advantages of augmentation with respect to primary in vitro stability and the clinical use for the proximal humerus are presented in this article. In this study six paired human humeri were randomized into an augmented and a non-augmented group. Osteosynthesis was performed with a PHILOS plate (Synthes®). In the augmented group the two screws finding purchase in the weakest cancellous bone were augmented. The specimens were tested in a 3-part fracture model in a varus bending test. The augmented PHILOS plates withstood significantly more load cycles until failure. The correlation to bone mineral density (BMD) showed that augmentation could partially compensate for low BMD. The augmentation of the screws in locked plating in a proximal humerus fracture model is effective in improving the primary stability in a cyclic varus bending test. The targeted augmentation of two particular screws in a region of low bone quality within the humeral head was almost as effective as four screws with twice the amount of bone cement. Screw augmentation combined with a knowledge of the local bone quality could be more effective in enhancing the primary stability of a proximal humerus locking plate because the effect of augmentation can be exploited more effectively limiting it to the degree required. The technique of augmentation is simple and can be applied in open and minimally invasive procedures. When the correct procedure is used, complications (cement leakage into the joint) can be avoided.

Augmented reality and ubiquitous computing : The hidden potentialities of augmented reality

NARCIS (Netherlands)

Liberati, Nicola

2016-01-01

The aim of this paper was to highlight the augmented reality’s potentialities, depicting its main characteristics and focusing attention on what its goal should be in order to have a new technology completely different from those that already exist. From a technological point of view, augmented

Capillary Refill using Augmented Reality

OpenAIRE

Clausen, Christoffer

2017-01-01

Master's thesis in Computer science The opportunities within augmented reality is growing. Augmented reality is a combination of the real and the virtual world in real time, and large companies like Microsoft and Google is now investing heavily in the technology. This thesis presents a solution for simulating a medical test called capillary refill, by using augmented reality. The simulation is performed with an augmented reality headset called HoloLens. The HoloLens will recognise a mark...

Mast cells, peptides and cardioprotection - an unlikely marriage?

LENUS (Irish Health Repository)

Walsh, S K

2012-01-31

1 Mast cells have classically been regarded as the \\'bad guys\\' in the setting of acute myocardial ischaemia, where their released contents are believed to contribute both to tissue injury and electrical disturbances resulting from ischaemia. Recent evidence suggests, however, that if mast cell degranulation occurs in advance of ischaemia onset, this may be cardioprotective by virtue of the depletion of mast cell contents that can no longer act as instruments of injury when the tissue becomes ischaemic. 2 Many peptides, such as ET-1, adrenomedullin, relaxin and atrial natriuretic peptide, have been demonstrated to be cardioprotective when given prior to the onset of myocardial ischaemia, although their physiological functions are varied and the mechanisms of their cardioprotective actions appear to be diverse and often ill defined. However, one common denominator that is emerging is the ability of these peptides to modulate mast cell degranulation, raising the possibility that peptide-induced mast cell degranulation or stabilization may hold the key to a common mechanism of their cardioprotection. 3 The aim of this review was to consolidate the evidence implying that mast cell degranulation could play both a detrimental and protective role in myocardial ischaemia, depending upon when it occurs, and that this may underlie the cardioprotective effects of a range of diverse peptides that exerts physiological effects within the cardiovascular system.

Regulation of somatostatin release in the nervous system of the rat

International Nuclear Information System (INIS)

Sheppard, M.

1979-08-01

This thesis represents the work done to study the release of somatostatin from the rat central nervous system in vitro, providing some evidence for a physiological role for somatostatin. Somatostatin was measured by a sensitive and specific radioimmunoassay devoloped in the laboratory. Chapter 2 reviews the literature on hypothalamic peptides and control of an anterior pituitary function, somatostatin, other central nervous system peptides and neurosecretion. Chapter 3 describes the central nervous system tissue dissection technique, the radioimmunoassay for somatostatin and the tissue levels of somatostatin immunoreactivity in different areas of the central nervous system. Chapter 4 deals with the release of immunoreactive somatostatin from incubated rat hypothalamus in vitro and the influence of other hormones and neuropeptides on this release. Chapter 5 describes the preparation of isolated nerve endings (synaptosomes) from four different areas of rat brain, the localisation of somatostatin to the synaptosome fraction of brain homogenates and the release of somatostatin from these synaptosomes. Chapter 6 deals with the release of somatostatin from incubated rat spinal cord in vitro. Chapter 7 presents the results of the characterisation of released immunoreactive material, the technique utilised being serial dilution of immunoreactive material and comparison to the standard curve, Sephadex gel chromatography, affinity chromatography, and the effect of released immunoreactive somatostatin on growth hormone release from perifused hemipituitaries in vitro, i.e. biological activity. Chapter 8 provides a summary of the main conclusions reached in this study and is followed by the Appendix describing chemical and biochemical methods, histological techniques, and statistical methods

Synthesis of human pancreatic growth hormone-releasing factor and two omission analogs by segment-coupling method in aqueous solution

Energy Technology Data Exchange (ETDEWEB)

Blake, J.; Westphal, M.; Li, C.H. (Laboratory of Molecular Endocrinology, University of California, San Francisco, USA)

1984-01-01

The human growth hormone-releasing factor (GRF) peptides (GlyS/sup 15/)-GRF-(1-15) (IV), trifluoroacetyl-GRF-(20-44) (VI), trifluoroacetyl-GRF-(18-44) (VIII), and trifluoroacetyl-GRF-(16-44) (X) were synthesized by the solidphase method. Each of the peptides was reacted with citraconic anhydride and the trifluoroacetyl group was removed by reaction with 10% hydrazine in water. The citraconylated GRF-(1-15) peptide was coupled to the (20-44), (18-44) or (16-44) peptides by reaction with silver nitrate/N-hydroxysuccinimide to give GRF-(1-15)-(20-44) (XII), GRF-(1-15)-(18-44) (XIII), or GRF-(1-44), respectively. GRF-(1-44) was shown to stimulate the release of rat growth hormone from rat pituitary cells with an ED/sub 50/=8.8 x 10/sup -11/M. Peptides XII and XIII were inactive, either as agonists or as antagonists of the action of GRF-(1-44).

Infusion of exogenous cholecystokinin-8, gastrin releasing peptide-29 and their combination reduce body weight in diet-induced obese male rats.

Science.gov (United States)

Mhalhal, Thaer R; Washington, Martha C; Newman, Kayla; Heath, John C; Sayegh, Ayman I

2017-02-01

We hypothesized that exogenous gastrin releasing peptide-29 (GRP-29), cholecystokinin-8 (CCK-8) and their combination reduce body weight (BW). To test this hypothesis, BW was measured in four groups of diet-induced obese (DIO) male rats infused in the aorta (close to the junctions of the celiac and cranial mesenteric arteries) with saline, CCK-8 (0.5 nmol/kg), GRP-29 (0.5 nmol/kg) and CCK-8+GRP-29 (0.5 nmol/kg each) once daily for a total of 23 days. We found that CCK-8, GRP-29 and CCK-8+GRP-29 reduce BW relative to saline control. In conclusion, CCK-8, GRP-29 and their combination reduce BW in the DIO rat model. If infused near their gastrointestinal sites of action CCK-8, GRP-29 and their combination may have a role in regulating BW. Published by Elsevier Ltd.

A Trojan-Horse Peptide-Carboxymethyl-Cytidine Antibiotic from Bacillus amyloliquefaciens.

Science.gov (United States)

Serebryakova, Marina; Tsibulskaya, Darya; Mokina, Olga; Kulikovsky, Alexey; Nautiyal, Manesh; Van Aerschot, Arthur; Severinov, Konstantin; Dubiley, Svetlana

2016-12-07

Microcin C and related antibiotics are Trojan-horse peptide-adenylates. The peptide part is responsible for facilitated transport inside the sensitive cell, where it gets processed to release a toxic warhead-a nonhydrolyzable aspartyl-adenylate, which inhibits aspartyl-tRNA synthetase. Adenylation of peptide precursors is carried out by MccB THIF-type NAD/FAD adenylyltransferases. Here, we describe a novel microcin C-like compound from Bacillus amyloliquefaciens. The B. amyloliquefaciens MccB demonstrates an unprecedented ability to attach a terminal cytidine monophosphate to cognate precursor peptide in cellular and cell free systems. The cytosine moiety undergoes an additional modification-carboxymethylation-that is carried out by the C-terminal domain of MccB and the MccS enzyme that produces carboxy-SAM, which serves as a donor of the carboxymethyl group. We show that microcin C-like compounds carrying terminal cytosines are biologically active and target aspartyl-tRNA synthetase, and that the carboxymethyl group prevents resistance that can occur due to modification of the warhead. The results expand the repertoire of known enzymatic modifications of peptides that can be used to obtain new biological activities while avoiding or limiting bacterial resistance.

A Review on Recent Advances in Stabilizing Peptides/Proteins upon Fabrication in Hydrogels from Biodegradable Polymers

Directory of Open Access Journals (Sweden)

Faisal Raza

2018-01-01

Full Text Available Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to overcome the shortcomings of old conventional dosage forms for small drugs (NSAIDS and large peptides and proteins. The aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. Peptide and proteins are remarkable therapeutic agents in today’s world that allow the treatment of severe, chronic and life-threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. Novels drug delivery systems composed of smart peptides and molecules have the ability to drive self-assembly and form hydrogels at physiological pH. These hydrogels are significantly important for biological and medical fields. The primary objective of this article is to review current issues concerned with the therapeutic peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. Recent advances based on various approaches like self-assembly of peptides and small molecules to form novel hydrogels are also discussed. The article will also review the literature concerning the classification of hydrogels on a different basis, polymers used, “release mechanisms” their physical and chemical characteristics and diverse applications.

Estimating ionospheric delay using kriging: 2. Impact on satellite-based augmentation system availability

Science.gov (United States)

Sparks, Lawrence; Blanch, Juan; Pandya, Nitin

2011-12-01

An augmentation of the Global Positioning System, the Wide Area Augmentation System (WAAS) broadcasts, at each node of an ionospheric grid, an estimate of the vertical ionospheric delay and an integrity bound on the vertical delay error. To date, these quantities have been determined from a planar fit of slant delay measurements, projected to vertical using an obliquity factor specified by the standard thin shell model of the ionosphere. In a future WAAS upgrade (WAAS Follow-On Release 3), however, they will be calculated using an established, geo-statistical estimation technique known as kriging that generally provides higher estimate accuracy than planar fit estimation. This paper analyzes the impact of kriging on system availability. In a preliminary assessment, kriging is found to produce improvements in availability of up to 15%.

Determination of Disulfide Bond Connectivity of Cysteine-rich Peptide IpTx{sub a}

Energy Technology Data Exchange (ETDEWEB)

Lee, Chul Won; Kim, Jim Il [Chonnam National Univ., Gwangju (Korea, Republic of); Sato, Kazuki [Fukuoka Women' s Univ., Fukuoka (Japan)

2013-06-15

Cysteine-rich peptides stabilized by intramolecular disulfide bonds have often been isolated from venoms of microbes, animals and plants. These peptides typically have much higher stability and improved biopharmaceutical properties compared to their linear counterparts. Therefore the correct disulfide bond formation of small proteins and peptides has been extensively studied for a better understanding of their folding mechanism and achieving efficient generation of the naturally occurring biologically active product. Imperatoxin A (IpTx{sub a}), a peptide toxin containing 6 cysteine residues, was isolated from the venom of scorpion Pandinus imperator, selectively binds the ryanodine receptors and activates Ca{sup 2+} release from sarcoplasmic reticulum (SR). IpTx{sub a} increases the binding of ryanodine to ryanodine receptors (RyRs) and encourages reconstituted single channel to induce subconductance states.

Incretin physiology beyond glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide: cholecystokinin and gastrin peptides

DEFF Research Database (Denmark)

Rehfeld, J F

2011-01-01

and neonatal islets express significant amounts of gastrin, and human as well as porcine islet cells express the gastrin/CCK-B receptor abundantly. Therefore, exogenous gastrin and CCK peptides stimulate insulin and glucagon secretion in man. Accordingly, endogenous hypergastrinaemia is accompanied by islet...... cell hyperplasia and increased insulin secretion. Conventionally, the effect of gastrointestinal hormones on insulin secretion (the incretin effect) has been defined and quantified in relation to oral versus intravenous glucose loadings. Under these unphysiological conditions, the release of gastrin...

Augmented Mirror: Interactive Augmented Reality System Based on Kinect

OpenAIRE

Vera , Lucía; Gimeno , Jesús; Coma , Inmaculada; Fernández , Marcos

2011-01-01

Part 1: Long and Short Papers; International audience; In this paper we present a virtual character controlled by an actor in real time, who talks with an audience through an augmented mirror. The application, which integrates video images, the avatar and other virtual objects within an Augmented Reality system, has been implemented using a mixture of technologies: two kinect systems for motion capture, depth map and real images, a gyroscope to detect head movements, and control algorithms to...

Augmented reality in neurosurgery.

Science.gov (United States)

Tagaytayan, Raniel; Kelemen, Arpad; Sik-Lanyi, Cecilia

2018-04-01

Neurosurgery is a medical specialty that relies heavily on imaging. The use of computed tomography and magnetic resonance images during preoperative planning and intraoperative surgical navigation is vital to the success of the surgery and positive patient outcome. Augmented reality application in neurosurgery has the potential to revolutionize and change the way neurosurgeons plan and perform surgical procedures in the future. Augmented reality technology is currently commercially available for neurosurgery for simulation and training. However, the use of augmented reality in the clinical setting is still in its infancy. Researchers are now testing augmented reality system prototypes to determine and address the barriers and limitations of the technology before it can be widely accepted and used in the clinical setting.

The exaggerated glucagon-like peptide-1 response is important for the improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes

DEFF Research Database (Denmark)

Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N

2013-01-01

β-cell function is improved in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to an exaggerated glucagon-like peptide 1 (GLP-1) secretion, but causality has not been established. The aim of this study...... consisted of two experimental days, allowing a meal test with infusion of saline or Ex-9 in random order. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased and glucagon secretion was augmented. GLP-1R blockade did not affect β......-cell function and meal-induced glucagon release before the operation, but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance...

Growth hormone-releasing factor stimulates proliferation of somatotrophs in vitro

DEFF Research Database (Denmark)

Billestrup, Nils; Swanson, L W; Vale, W

1986-01-01

The mitogenic effect of the hypothalamic peptides growth hormone-releasing factor (GRF) and somatostatin on cultured growth hormone (GH)-producing cells (somatotrophs) was studied. Using autoradiographic detection of [3H]thymidine uptake and immunocytochemical identification of GH-producing cells...

AR DOC: Augmented reality documentaries

DEFF Research Database (Denmark)

Vistisen, Peter

2014-01-01

Augmented Reality Documentaries (AR DOC) er et ’lille’ Shareplay projekt (ansøgte midler augmented reality cross media løsninger, til at skabe engagerende publikumsformidling...... indenfor oplevelsesindustrien. Projektet har genereret ny viden omkring, hvordan fysisk og digital formidling kan understøttes via Augmented Reality som formidlingsformat....

Production of an antimicrobial peptide derived from slaughterhouse by-product and its potential application on meat as preservative.

Science.gov (United States)

Przybylski, Rémi; Firdaous, Loubna; Châtaigné, Gabrielle; Dhulster, Pascal; Nedjar, Naïma

2016-11-15

Bovine cruor, a slaughterhouse by-product, contains mainly hemoglobin, broadly described as a rich source of antimicrobial peptides. In the current context of food safety, bioactive peptides could be of interest as preservatives in the distribution of food products. The aim of this work was to study the α137-141 fragment of hemoglobin (Thr-Ser-Lys-Tyr-Arg), a small (653Da) and hydrophilic antimicrobial peptide. Its production was fast, with more 65% finally produced at 24h already produced after 30min of hydrolysis with pepsin. Moreover, increasing substrate concentration (from 1 to 8% (w/v)) resulted in a proportional augmentation of α137-141 production (to 807.95±41.03mgL(-1)). The α137-141 application on meat as preservative (0.5%, w/w) reduced the lipid oxidation about 60% to delay meat rancidity. The α137-141 peptide also inhibited the microbial growths under refrigeration during 14days. These antimicrobial effects were close to those of the butylated hydroxytoluene (BHT). Copyright © 2016 Elsevier Ltd. All rights reserved.

Crystal structure of a TAPBPR–MHC I complex reveals the mechanism of peptide editing in antigen presentation

Energy Technology Data Exchange (ETDEWEB)

Jiang, Jiansheng; Natarajan, Kannan; Boyd, Lisa F.; Morozov, Giora I.; Mage, Michael G.; Margulies, David H. (NIH); (Hebrew)

2017-10-12

Central to CD8+ T cell–mediated immunity is the recognition of peptide–major histocompatibility complex class I (p–MHC I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC I is a key step in the MHC I antigen presentation pathway. However, the structure of MHC I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC I in complex with the peptide editor TAPBPR (TAP-binding protein–related), a tapasin homolog. TAPBPR remodels the peptide-binding groove of MHC I, resulting in the release of low-affinity peptide. Changes include groove relaxation, modifications of key binding pockets, and domain adjustments. This structure captures a peptide-receptive state of MHC I and provides insights into the mechanism of peptide editing by TAPBPR and, by analogy, tapasin.

Problems Inherent to Augmentation of Natural Enemies in Open Agriculture.

Science.gov (United States)

Michaud, J P

2018-04-01

Augmentation biological control has successfully replaced a lot of insecticide use in 'closed system' agriculture (e.g., greenhouses). The profitable commercialization of biocontrol agents in greenhouses has created an incentive to expand markets for mass-reared beneficial insects into open agricultural systems, often without sufficient scientific justification. However, the semi-contained nature of greenhouse culture is often critical to the success of augmentation and can serve to mask potential pitfalls and intrinsic limitations of this approach in open systems. Factors contributing to greenhouse successes include the reduced biological diversity of contained agroecosystems, the prevention of agent dispersal, the ability to maintain environmental conditions within a range favorable for the agent, the exclusion of competitors and natural enemies of the agent that might otherwise diminish its efficacy, and the absence of alternative prey/hosts that could divert predation/parasitism from the target pest. There are also problems arising from collection of source material from locally adapted populations, and the inadvertent imposition of artificial selection in the course of laboratory rearing. Besides highlighting these pitfalls, this paper aims to encourage more consideration of conservation approaches prior to investment in augmentation programs which entice farmers into perpetual cycles of 'rear and release.' I argue that although augmentation can benefit agriculture whenever it replaces pesticide applications, it does not constitute an ecologically sustainable solution because it requires continued inputs, and it can distract research attention away from more sustainable objectives. Sustainable biological control is best achieved through modifications to cultural practices that increasingly 'naturalize' agroecosystems, thus facilitating the natural recruitment and persistence of beneficial arthropod fauna, combined with habitat management geared to increasing

Characterization and identification of novel antidiabetic and anti-obesity peptides from camel milk protein hydrolysates.

Science.gov (United States)

Mudgil, Priti; Kamal, Hina; Yuen, Gan Chee; Maqsood, Sajid

2018-09-01

In-vitro inhibitory properties of peptides released from camel milk proteins against dipeptidyl peptidase-IV (DPP-IV), porcine pancreatic α-amylase (PPA), and porcine pancreatic lipase (PPL) were studied. Results revealed that upon hydrolysis by different enzymes, camel milk proteins displayed dramatic increase in inhibition of DPP-IV and PPL, but slight improvement in PPA inhibition was noticed. Peptide sequencing revealed a total of 20 and 3 peptides for A9 and B9 hydrolysates respectively, obtained the score of 0.8 or more on peptide ranker and were categorized as potential DPP-IV inhibitory peptides. KDLWDDFKGL in A9 and MPSKPPLL in B9 were identified as most potent PPA inhibitory peptide. For PPL inhibition only 7 and 2 peptides qualified as PPL inhibitory peptides from hydrolysates A9 and B9, respectively. The present study report for the first time PPA and PPL inhibitory and only second for DPP-IV inhibitory potential of protein hydrolysates from camel milk. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

Directory of Open Access Journals (Sweden)

Andreas Bayer

2017-01-01

Full Text Available Platelet-released growth factors (PRGF and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF® contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3 is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR. In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds.

The Antimicrobial Peptide Human Beta-Defensin-3 Is Induced by Platelet-Released Growth Factors in Primary Keratinocytes

Science.gov (United States)

Lammel, Justus; Tohidnezhad, Mersedeh; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Cremer, Jochen; Jahr, Holger; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Platelet-released growth factors (PRGF) and its related clinically used formulations (e.g., Vivostat Platelet-Rich Fibrin (PRF®)) contain a variety of chemokines, cytokines, and growth factors and are therefore used to support healing of chronic, hard-to-heal, or infected wounds. Human beta-defensin-3 (hBD-3) is an antimicrobial peptide inducibly expressed in human keratinocytes especially upon wounding. The potent antimicrobial activity of hBD-3 together with its wound closure-promoting activities suggests that hBD-3 may play a crucial role in wound healing. Therefore, we analyzed the influence of PRGF on hBD-3 expression in human primary keratinocytes in vitro. In addition, we investigated the influence of Vivostat PRF on hBD-3 expression in artificially generated human skin wounds in vivo. PRGF treatment of primary keratinocytes induced a significant, concentration- and time-dependent increase in hBD-3 gene expression which was partially mediated by the epidermal growth factor receptor (EGFR). In line with these cell culture data, in vivo experiments revealed an enhanced hBD-3 expression in experimentally produced human wounds after the treatment with Vivostat PRF. Thus, the induction of hBD-3 may contribute to the beneficial effects of thrombocyte concentrate lysates in the treatment of chronic or infected wounds. PMID:28811680

The effects of weekly augmentation therapy in patients with PiZZ α1-antitrypsin deficiency

Directory of Open Access Journals (Sweden)

Schmid ST

2012-09-01

-6, tumor necrosis factor- α, and vascular endothelial growth factor within a week of augmentation therapy. In general, augmented individuals had higher AAT and lower serum levels of IL-8 than nonaugmented subjects. Prolastin added for 3 hours to neutrophils from protease inhibitor phenotype ZZ individuals in vitro reduced IL-8 release but showed no effect on cytokine/chemokine release from human bronchial epithelial cells.Conclusion: Within a week, augmentation with Prolastin induced fluctuations in serum levels of AAT polymers and cytokine/chemokines but specifically lowered IL-8 levels. It remains to be determined whether these effects are related to the Prolastin preparation per se or to the therapeutic efficacy of augmentation with AAT.Keywords: Prolastin, augmentation therapy, cytokines, IL-8, exhaled breath condensate, neutrophils

Crime Scenes as Augmented Reality

DEFF Research Database (Denmark)

Sandvik, Kjetil

2010-01-01

Using the concept of augmented reality, this article will investigate how places in various ways have become augmented by means of different mediatization strategies. Augmentation of reality implies an enhancement of the places' emotional character: a certain mood, atmosphere or narrative surplus......, physical damage: they are all readable and interpretable signs. As augmented reality the crime scene carries a narrative which at first is hidden and must be revealed. Due to the process of investigation and the detective's ability to reason and deduce, the crime scene as place is reconstructed as virtual...

Synergistic gene and drug tumor therapy using a chimeric peptide.

Science.gov (United States)

Han, Kai; Chen, Si; Chen, Wei-Hai; Lei, Qi; Liu, Yun; Zhuo, Ren-Xi; Zhang, Xian-Zheng

2013-06-01

Co-delivery of gene and drug for synergistic therapy has provided a promising strategy to cure devastating diseases. Here, an amphiphilic chimeric peptide (Fmoc)2KH7-TAT with pH-responsibility for gene and drug delivery was designed and fabricated. As a drug carrier, the micelles self-assembled from the peptide exhibited a much faster doxorubicin (DOX) release rate at pH 5.0 than that at pH 7.4. As a non-viral gene vector, (Fmoc)(2)KH(7)-TAT peptide could satisfactorily mediate transfection of pGL-3 reporter plasmid with or without the existence of serum in both 293T and HeLa cell-lines. Besides, the endosome escape capability of peptide/DNA complexes was investigated by confocal laser scanning microscopy (CLSM). To evaluate the co-delivery efficiency and the synergistic anti-tumor effect of gene and drug, p53 plasmid and DOX were simultaneously loaded in the peptide micelles to form micelleplexes during the self-assembly of the peptide. Cellular uptake and intracellular delivery of gene and drug were studied by CLSM and flow cytometry respectively. And p53 protein expression was determined via Western blot analysis. The in vitro cytotoxicity and in vivo tumor inhibition effect were also studied. Results suggest that the co-delivery of gene and drug from peptide micelles resulted in effective cell growth inhibition in vitro and significant tumor growth restraining in vivo. The chimeric peptide-based gene and drug co-delivery system will find great potential for tumor therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Oxidative stress augments toll-like receptor 8 mediated neutrophilic responses in healthy subjects

Directory of Open Access Journals (Sweden)

Matsunaga Kazuto

2009-06-01

Full Text Available Abstract Background Excessive oxidative stress has been reported to be generated in inflamed tissues and contribute to the pathogenesis of inflammatory lung diseases, exacerbations of which induced by viral infections are associated with toll-like receptor (TLR activation. Among these receptors, TLR8 has been reported as a key receptor that recognizes single-strand RNA virus. However, it remains unknown whether TLR8 signaling is potentiated by oxidative stress. The aim of this study is to examine whether oxidative stress modulates TLR8 signaling in vitro. Methods Human peripheral blood neutrophils were obtained from healthy non-smokers and stimulated with TLR 7/8 agonist imidazoquinoline resiquimod (R848 in the presence or absence of hydrogen peroxide (H2O2. Neutrophilic responses including cytokine release, superoxide production and chemotaxis were examined, and the signal transduction was also analyzed. Results Activation of TLR8, but not TLR7, augmented IL-8 release. The R848-augmented IL-8 release was significantly potentiated by pretreatment with H2O2 (p L-cysteine reversed this potentiation. The combination of H2O2 and R848 significantly potentiated NF-kB phosphorylation and IkBα degradation. The H2O2-potentiated IL-8 release was suppressed by MG-132, a proteosome inhibitor, and by dexamethasone. The expressions of TLR8, myeloid differentiation primary response gene 88 (MyD88, and tumor necrosis factor receptor-associated factor 6 (TRAF6 were not affected by H2O2. Conclusion TLR8-mediated neutrophilic responses were markedly potentiated by oxidative stress, and the potentiation was mediated by enhanced NF-kB activation. These results suggest that oxidative stress might potentiate the neutrophilic inflammation during viral infection.

Determination of growth hormone releasing peptides (GHRP) and their major metabolites in human urine for doping controls by means of liquid chromatography mass spectrometry.

Science.gov (United States)

Thomas, Andreas; Höppner, Sebastian; Geyer, Hans; Schänzer, Wilhelm; Petrou, Michael; Kwiatkowska, Dorota; Pokrywka, Andrzej; Thevis, Mario

2011-08-01

A family of small peptides has reached the focus of doping controls representing a comparably new strategy for cheating sportsmen. These growth hormone releasing peptides (GHRP) are orally active and induce an increased production of endogenous growth hormone (GH). While the established test for exogenous GH fails, the misuse of these prohibited substances remains unrecognized. The present study provides data for the efficient extraction of a variety of known drug candidates (GHRP-1, GHRP-2, GHRP-4, GHRP-5, GHRP-6, alexamorelin, ipamorelin, and hexarelin) from human urine with subsequent mass spectrometric detection after liquid chromatographic separation. The used method potentially enables the retrospective evaluation of the acquired data for unknown metabolites by means of a non-targeted approach with high-resolution/high-accuracy full-scan mass spectrometry with additional higher collision energy dissociation experiments. This is of great importance due to the currently unknown metabolism of most of the targets and, thus, the method is focused on the intact peptidic drugs. Only the already characterised major metabolite of GHRP-2 (D-Ala-D-2-naphthylAla-L-Ala, as well as its stable isotope-labelled analogue) was synthesised and implemented in the detection assay. Method validation for qualitative purpose was performed with respect to specificity, precision (<20%), intermediate precision (<20%), recovery (47-95%), limit of detection (0.2-1 ng/mL), linearity, ion suppression and stability. Two stable isotope-labelled internal standards were used (deuterium-labelled GHRP-4 and GHRP-2 metabolite). The proof-of-principle was obtained by the analysis of excretion study urine samples obtained from a single oral administration of 10 mg of GHRP-2. Here, the known metabolite was detectable over 20 h after administration while the intact drug was not observed.

Localization of receptors for bombesin-like peptides in the rat brain

International Nuclear Information System (INIS)

Moody, T.W.; Getz, R.; O'Donohue, T.L.; Rosenstein, J.M.

1988-01-01

BN-like peptides and receptors are present in discrete areas of the mammalian brain. By radioimmunoassay, endogenous BN/GRP, neuromedin B, and ranatensin-like peptides are present in the rat brain. High-to-moderate concentrations of BN/GRP are present in the rat hypothalamus and thalamus, whereas moderate-to-high densities of neuromedin B and ranatensin-like peptides are present in the olfactory bulb and hippocampus, as well as in the hypothalamus and thalamus. While the distribution of neuromedin B and ranatensin-like peptides appears similar, it is distinct from that of BN/GRP. When released from CNS neurons, these peptides may interact with receptors for BN-like peptides. BN, GRP, ranatensin, and neuromedin B inhibit specific [ 125 I-Tyr4]BN binding with high affinity. By use of in vitro autoradiographic techniques to detect binding of [ 125 I-Tyr4]BN to receptors for BN-like peptides, high grain densities were found in the olfactory bulb and tubercle, the nucleus accumbens, the suprachiasmatic and paraventricular nucleus of the hypothalamus, the central medial and paraventricular thalamic nuclei, the hippocampus, the dentate gyrus, and the amygdala of the rat brain. Some of these receptors may be biologically active and mediate the biological effects of BN-like peptides. For example, when BN is directly injected into the nucleus accumbens, pronounced grooming results and the effects caused by BN are reversed by spantide and [D-Phe12]BN. Thus, the putative BN receptor antagonists may serve as useful agents to investigate the biological significance of BN-like peptides in the CNS

Unprecedented high insulin secretion in a healthy human subject after intravenous glucagon-like peptide-1

DEFF Research Database (Denmark)

Knop, Filip K; Lund, Asger; Madsbad, Sten

2014-01-01

BACKGROUND: The gut-derived incretin hormones, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are released in response to ingestion of nutrients. Both hormones are highly insulinotropic in strictly glucose-dependent fashions and glucagon-like peptide-1 is often referred...... to as one of the most insulinotropic substances known. CASE PRESENTATION: Plasma insulin and C-peptide concentrations were measured in a healthy Caucasian male (age: 53 years; body mass index: 28.6 kg/m2; fasting plasma glucose: 5.7 mM; 2 h plasma glucose value following 75 g-oral glucose tolerance test: 3...

Mitochondrial N-formyl peptides induce cardiovascular collapse and sepsis-like syndrome

Science.gov (United States)

McCarthy, Cameron G.; Szasz, Theodora; Goulopoulou, Styliani; Webb, R. Clinton

2015-01-01

Fifty percent of trauma patients who present sepsis-like syndrome do not have bacterial infections. This condition is known as systemic inflammatory response syndrome (SIRS). A unifying factor of SIRS and sepsis is cardiovascular collapse. Trauma and severe blood loss cause the release of endogenous molecules known as damage-associated molecular patterns. Mitochondrial N-formyl peptides (F-MIT) are damage-associated molecular patterns that share similarities with bacterial N-formylated peptides and are potent immune system activators. The goal of this study was to investigate whether F-MIT trigger SIRS, including hypotension and vascular collapse via formyl peptide receptor (FPR) activation. We evaluated cardiovascular parameters in Wistar rats treated with FPR or histamine receptor antagonists and inhibitors of the nitric oxide pathway before and after F-MIT infusion. F-MIT, but not nonformylated peptides or mitochondrial DNA, induced severe hypotension via FPR activation and nitric oxide and histamine release. Moreover, F-MIT infusion induced hyperthermia, blood clotting, and increased vascular permeability. To evaluate the role of leukocytes in F-MIT-induced hypotension, neutrophil, basophil, or mast cells were depleted. Depletion of basophils, but not neutrophils or mast cells, abolished F-MIT-induced hypotension. Rats that underwent hemorrhagic shock increased plasma levels of mitochondrial formylated proteins associated with lung damage and antagonism of FPR ameliorated hemorrhagic shock-induced lung injury. Finally, F-MIT induced vasodilatation in isolated resistance arteries via FPR activation; however, F-MIT impaired endothelium-dependent relaxation in the presence of blood. These data suggest that F-MIT may be the link among trauma, SIRS, and cardiovascular collapse. PMID:25637548

Augmented reality: a review.

Science.gov (United States)

Berryman, Donna R

2012-01-01

Augmented reality is a technology that overlays digital information on objects or places in the real world for the purpose of enhancing the user experience. It is not virtual reality, that is, the technology that creates a totally digital or computer created environment. Augmented reality, with its ability to combine reality and digital information, is being studied and implemented in medicine, marketing, museums, fashion, and numerous other areas. This article presents an overview of augmented reality, discussing what it is, how it works, its current implementations, and its potential impact on libraries.

Peptides and Anti-peptide Antibodies for Small and Medium Scale Peptide and Anti-peptide Affinity Microarrays: Antigenic Peptide Selection, Immobilization, and Processing.

Science.gov (United States)

Zhang, Fan; Briones, Andrea; Soloviev, Mikhail

2016-01-01

This chapter describes the principles of selection of antigenic peptides for the development of anti-peptide antibodies for use in microarray-based multiplex affinity assays and also with mass-spectrometry detection. The methods described here are mostly applicable to small to medium scale arrays. Although the same principles of peptide selection would be suitable for larger scale arrays (with 100+ features) the actual informatics software and printing methods may well be different. Because of the sheer number of proteins/peptides to be processed and analyzed dedicated software capable of processing all the proteins and an enterprise level array robotics may be necessary for larger scale efforts. This report aims to provide practical advice to those who develop or use arrays with up to ~100 different peptide or protein features.

Vegetable foods: a cheap source of proteins and peptides with antihypertensive, antioxidant, and other less occurrence bioactivities.

Science.gov (United States)

García, M C; Puchalska, P; Esteve, C; Marina, M L

2013-03-15

Despite less explored than foods from animal origin, plant derived foods also contain biologically active proteins and peptides. Bioactive peptides can be present as an independent entity in the food or, more frequently, can be in a latent state as part of the sequence of a protein. Release from that protein requires protein hydrolysis by enzymatic digestion, fermentation or autolysis. Different methodologies have been used to test proteins and peptides bioactivities. Fractionation, separation, and identification techniques have also been employed for the isolation and identification of bioactive proteins or peptides. In this work, proteins and peptides from plant derived foods exerting antihypertensive, antioxidant, hypocholesterolemic, antithrombotic, and immunostimulating capacities or ability to reduce food intake have been reviewed. Copyright © 2013 Elsevier B.V. All rights reserved.

Peptide-laden mesoporous silica nanoparticles with promoted bioactivity and osteo-differentiation ability for bone tissue engineering.

Science.gov (United States)

Luo, Zuyuan; Deng, Yi; Zhang, Ranran; Wang, Mengke; Bai, Yanjie; Zhao, Qiang; Lyu, Yalin; Wei, Jie; Wei, Shicheng

2015-07-01

Combination of mesoporous silica materials and bioactive factors is a promising niche-mimetic solution as a hybrid bone substitution for bone tissue engineering. In this work, we have synthesized biocompatible silica-based nanoparticles with abundant mesoporous structure, and incorporated bone-forming peptide (BFP) derived from bone morphogenetic protein-7 (BMP-7) into the mesoporous silica nanoparticles (MSNs) to obtain a slow-release system for osteogenic factor delivery. The chemical characterization demonstrates that the small osteogenic peptide is encapsulated in the mesoporous successfully, and the nitrogen adsorption-desorption isotherms suggest that the peptide encapsulation has no influence on mesoporous structure of MSNs. In the cell experiment, the peptide-laden MSNs (p-MSNs) show higher MG-63 cell proliferation, spreading and alkaline phosphatase (ALP) activity than the bare MSNs, indicating good in vitro cytocompatibility. Simultaneously, the osteogenesis-related proteins expression and calcium mineral deposition disclose enhanced osteo-differentiation of human mesenchymal stem cells (hMSCs) under the stimulation of the p-MSNs, confirming that BFP released from MSNs could significantly promote the osteogenic differentiation of hMSCs, especially at 500μg/mL of p-MSNs concentration. The peptide-modified MSNs with better bioactivity and osteogenic differentiation make it a potential candidate as bioactive material for bone repairing, bone regeneration, and bio-implant coating applications. Copyright © 2015 Elsevier B.V. All rights reserved.

Generation in vivo of peptide-specific cytotoxic T cells and presence of regulatory T cells during vaccination with hTERT (class I and II peptide-pulsed DCs

Directory of Open Access Journals (Sweden)

Satthaporn Sukchai

2009-03-01

Full Text Available Abstract Background Optimal techniques for DC generation for immunotherapy in cancer are yet to be established. Study aims were to evaluate: (i DC activation/maturation milieu (TNF-α +/- IFN-α and its effects on CD8+ hTERT-specific T cell responses to class I epitopes (p540 or p865, (ii CD8+ hTERT-specific T cell responses elicited by vaccination with class I alone or both class I and II epitope (p766 and p672-pulsed DCs, prepared without IFN-α, (iii association between circulating T regulatory cells (Tregs and clinical responses. Methods Autologous DCs were generated from 10 patients (HLA-0201 with advanced cancer by culturing CD14+ blood monocytes in the presence of GM-CSF and IL-4 supplemented with TNF-α [DCT] or TNF-α and IFN-α [DCTI]. The capacity of the DCs to induce functional CD8+ T cell responses to hTERT HLA-0201 restricted nonapeptides was assessed by MHC tetramer binding and peptide-specific cytotoxicity. Each DC preparation (DCT or DCTI was pulsed with only one type of hTERT peptide (p540 or p865 and both preparations were injected into separate lymph node draining regions every 2–3 weeks. This vaccination design enabled comparison of efficacy between DCT and DCTI in generating hTERT peptide specific CD8+ T cells and comparison of class I hTERT peptide (p540 or p865-loaded DCT with or without class II cognate help (p766 and p672 in 6 patients. T regulatory cells were evaluated in 8 patients. Results (i DCTIs and DCTs, pulsed with hTERT peptides, were comparable (p = 0.45, t-test in inducing peptide-specific CD8+ T cell responses. (ii Class II cognate help, significantly enhanced (p (iii Clinical responders had significantly lower (p Conclusion Addition of IFN-α to ex vivo monocyte-derived DCs, did not significantly enhance peptide-specific T cell responses in vivo, compared with TNF-α alone. Class II cognate help significantly augments peptide-specific T cell responses. Clinically favourable responses were seen in patients

Therapeutic peptides for cancer therapy. Part II - cell cycle inhibitory peptides and apoptosis-inducing peptides.

Science.gov (United States)

Raucher, Drazen; Moktan, Shama; Massodi, Iqbal; Bidwell, Gene L

2009-10-01

Therapeutic peptides have great potential as anticancer agents owing to their ease of rational design and target specificity. However, their utility in vivo is limited by low stability and poor tumor penetration. The authors review the development of peptide inhibitors with potential for cancer therapy. Peptides that arrest the cell cycle by mimicking CDK inhibitors or induce apoptosis directly are discussed. The authors searched Medline for articles concerning the development of therapeutic peptides and their delivery. Inhibition of cancer cell proliferation directly using peptides that arrest the cell cycle or induce apoptosis is a promising strategy. Peptides can be designed that interact very specifically with cyclins and/or cyclin-dependent kinases and with members of apoptotic cascades. Use of these peptides is not limited by their design, as a rational approach to peptide design is much less challenging than the design of small molecule inhibitors of specific protein-protein interactions. However, the limitations of peptide therapy lie in the poor pharmacokinetic properties of these large, often charged molecules. Therefore, overcoming the drug delivery hurdles could open the door for effective peptide therapy, thus making an entirely new class of molecules useful as anticancer drugs.

Structure of the superantigen staphylococcal enterotoxin B in complex with TCR and peptide-MHC demonstrates absence of TCR-peptide contacts.

Science.gov (United States)

Rödström, Karin E J; Elbing, Karin; Lindkvist-Petersson, Karin

2014-08-15

Superantigens are immune-stimulatory toxins produced by Staphylococcus aureus, which are able to interact with host immune receptors to induce a massive release of cytokines, causing toxic shock syndrome and possibly death. In this article, we present the x-ray structure of staphylococcal enterotoxin B (SEB) in complex with its receptors, the TCR and MHC class II, forming a ternary complex. The structure, in combination with functional analyses, clearly shows how SEB adopts a wedge-like position when binding to the β-chain of TCR, allowing for an interaction between the α-chain of TCR and MHC. Furthermore, the binding mode also circumvents contact between TCR and the peptide presented by MHC, which enables SEB to initiate a peptide-independent activation of T cells. Copyright © 2014 by The American Association of Immunologists, Inc.

Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity

Science.gov (United States)

Lim, Seng Koon; Sandén, Camilla; Selegård, Robert; Liedberg, Bo; Aili, Daniel

2016-02-01

Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore-formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo.

The physiology of glucagon-like peptide 1

DEFF Research Database (Denmark)

Holst, Jens Juul

2007-01-01

Glucagon-like peptide 1 (GLP-1) is a 30-amino acid peptide hormone produced in the intestinal epithelial endocrine L-cells by differential processing of proglucagon, the gene which is expressed in these cells. The current knowledge regarding regulation of proglucagon gene expression in the gut...... and in the brain and mechanisms responsible for the posttranslational processing are reviewed. GLP-1 is released in response to meal intake, and the stimuli and molecular mechanisms involved are discussed. GLP-1 is extremely rapidly metabolized and inactivated by the enzyme dipeptidyl peptidase IV even before...... postprandial glucose excursions. It also inhibits gastrointestinal motility and secretion and thus acts as an enterogastrone and part of the "ileal brake" mechanism. GLP-1 also appears to be a physiological regulator of appetite and food intake. Because of these actions, GLP-1 or GLP-1 receptor agonists...

Characterization of trypsin-derived peptides acrylamide-adducted hemoglobin

International Nuclear Information System (INIS)

Springer, D.L.; Goheen, S.C.; Edmonds, C.G.; McCulloch, M.; Sylvester, D.M.; Sander, C.; Bull, R.J.

1991-01-01

Even though there are a number of sources for human exposure to acrylamide, reliable biomarkers of exposure are not available. In an effort to develop such a biomarker, the authors are characterizing peptides derived from trypsin digests of acrylamide-adducted hemoglobin. For this, radiolabeled acrylamide was incubated with this, radiolabeled acrylamide was incubated with purified human hemoglobin (Ao) and decomposition products removed by dialysis. When the adducted hemoglobin was separated by reverse-phase HPLC, radioactivity eluted with the α and β subunits, suggesting covalent binding. Digestion of individual subunits with trypsin followed by reverse phase HPLC, indicated that most of the radioactivity associated with the α subunit co-eluted with a single peptide. Similar results were observed for the β subunit except that significant amounts of radioactivity eluted with the solvent front, suggesting that radioactivity was released by trypsin digestion. Currently, these preparation are under further characterization by electrospray ionization mass spectrometry. This approach will aid in the identification of the adducted will aid in the identification of the adducted peptide and subsequent preparation of an acrylamide-specific antibody

Use of Augmented Reality in Education

OpenAIRE

Jeřábek, Tomáš

2014-01-01

This thesis deals with phenomena of augmented reality in context of didactics. The thesis aims to define augmented reality in conceptual and content area and focuses on augmented reality in the structure of educational tools and identification of its functions and use from the didactical standpoint. The thesis characterizes augmented reality as a specific technological-perceptual concept and establishes a system of perceptual, technological and resulting aspects that reflect important paramet...

Peptides, polypeptides and peptide-polymer hybrids as nucleic acid carriers.

Science.gov (United States)

Ahmed, Marya

2017-10-24

Cell penetrating peptides (CPPs), and protein transduction domains (PTDs) of viruses and other natural proteins serve as a template for the development of efficient peptide based gene delivery vectors. PTDs are sequences of acidic or basic amphipathic amino acids, with superior membrane trespassing efficacies. Gene delivery vectors derived from these natural, cationic and cationic amphipathic peptides, however, offer little flexibility in tailoring the physicochemical properties of single chain peptide based systems. Owing to significant advances in the field of peptide chemistry, synthetic mimics of natural peptides are often prepared and have been evaluated for their gene expression, as a function of amino acid functionalities, architecture and net cationic content of peptide chains. Moreover, chimeric single polypeptide chains are prepared by a combination of multiple small natural or synthetic peptides, which imparts distinct physiological properties to peptide based gene delivery therapeutics. In order to obtain multivalency and improve the gene delivery efficacies of low molecular weight cationic peptides, bioactive peptides are often incorporated into a polymeric architecture to obtain novel 'polymer-peptide hybrids' with improved gene delivery efficacies. Peptide modified polymers prepared by physical or chemical modifications exhibit enhanced endosomal escape, stimuli responsive degradation and targeting efficacies, as a function of physicochemical and biological activities of peptides attached onto a polymeric scaffold. The focus of this review is to provide comprehensive and step-wise progress in major natural and synthetic peptides, chimeric polypeptides, and peptide-polymer hybrids for nucleic acid delivery applications.

Bayesian Alternation During Tactile Augmentation

Directory of Open Access Journals (Sweden)

Caspar Mathias Goeke

2016-10-01

Full Text Available A large number of studies suggest that the integration of multisensory signals by humans is well described by Bayesian principles. However, there are very few reports about cue combination between a native and an augmented sense. In particular, we asked the question whether adult participants are able to integrate an augmented sensory cue with existing native sensory information. Hence for the purpose of this study we build a tactile augmentation device. Consequently, we compared different hypotheses of how untrained adult participants combine information from a native and an augmented sense. In a two-interval forced choice (2 IFC task, while subjects were blindfolded and seated on a rotating platform, our sensory augmentation device translated information on whole body yaw rotation to tactile stimulation. Three conditions were realized: tactile stimulation only (augmented condition, rotation only (native condition, and both augmented and native information (bimodal condition. Participants had to choose one out of two consecutive rotations with higher angular rotation. For the analysis, we fitted the participants’ responses with a probit model and calculated the just notable difference (JND. Then we compared several models for predicting bimodal from unimodal responses. An objective Bayesian alternation model yielded a better prediction (χred2 = 1.67 than the Bayesian integration model (χred2= 4.34. Slightly higher accuracy showed a non-Bayesian winner takes all model (χred2= 1.64, which either used only native or only augmented values per subject for prediction. However the performance of the Bayesian alternation model could be substantially improved (χred2= 1.09 utilizing subjective weights obtained by a questionnaire. As a result, the subjective Bayesian alternation model predicted bimodal performance most accurately among all tested models. These results suggest that information from augmented and existing sensory modalities in

Augmented Performance Environment for Enhancing Interagency Coordination in Stability, Security, Transition, and Reconstruction (SSTR) Operations: Phase 2

Science.gov (United States)

2010-12-01

motivating participation, and smoothing interactions. The recollections of these subject matter experts suggested that prosocial orientation (i.e...U.S. Army Research Institute for the Behavioral and Social Sciences Research Report 1934 Augmented performance...release; distribution is unlimited. U.S. Army Research Institute for the Behavioral and Social Sciences Department of the Army Deputy

Augmented Reality

DEFF Research Database (Denmark)

Kjærgaard, Hanne Wacher; Kjeldsen, Lars Peter Bech; Rahn, Annette

2015-01-01

This chapter describes the use of iPad-facilitated application of augmented reality in the teaching of highly complex anatomical and physiological subjects in the training of nurses at undergraduate level. The general aim of the project is to investigate the potentials of this application in terms...... of making the complex content and context of these subjects more approachable to the students through the visualization made possible through the use of this technology. A case study is described in this chapter. Issues and factors required for the sustainable use of the mobile-facilitated application...... of augmented reality are discussed....

Affordances in Mobile Augmented Reality Applications

OpenAIRE

Gjøsæter, Tor

2014-01-01

This paper explores the affordances of augmented reality content in a mobile augmented reality application. A user study was conducted by performing a multi-camera video recording of seven think aloud sessions. The think aloud sessions consisted of individual users performing tasks, exploring and experiencing a mobile augmented reality (MAR) application we developed for the iOS platform named ARad. We discuss the instrumental affordances we observed when users interacted with augmented realit...

Dynamic augmentation restores anterior tibial translation in ACL suture repair: a biomechanical comparison of non-, static and dynamic augmentation techniques.

Science.gov (United States)

Hoogeslag, Roy A G; Brouwer, Reinoud W; Huis In 't Veld, Rianne; Stephen, Joanna M; Amis, Andrew A

2018-02-03

There is a lack of objective evidence investigating how previous non-augmented ACL suture repair techniques and contemporary augmentation techniques in ACL suture repair restrain anterior tibial translation (ATT) across the arc of flexion, and after cyclic loading of the knee. The purpose of this work was to test the null hypotheses that there would be no statistically significant difference in ATT after non-, static- and dynamic-augmented ACL suture repair, and they will not restore ATT to normal values across the arc of flexion of the knee after cyclic loading. Eleven human cadaveric knees were mounted in a test rig, and knee kinematics from 0° to 90° of flexion were recorded by use of an optical tracking system. Measurements were recorded without load and with 89-N tibial anterior force. The knees were tested in the following states: ACL-intact, ACL-deficient, non-augmented suture repair, static tape augmentation and dynamic augmentation after 10 and 300 loading cycles. Only static tape augmentation and dynamic augmentation restored ATT to values similar to the ACL-intact state directly postoperation, and maintained this after cyclic loading. However, contrary to dynamic augmentation, the ATT after static tape augmentation failed to remain statistically less than for the ACL-deficient state after cyclic loading. Moreover, after cyclic loading, ATT was significantly less with dynamic augmentation when compared to static tape augmentation. In contrast to non-augmented ACL suture repair and static tape augmentation, only dynamic augmentation resulted in restoration of ATT values similar to the ACL-intact knee and decreased ATT values when compared to the ACL-deficient knee immediately post-operation and also after cyclic loading, across the arc of flexion, thus allowing the null hypotheses to be rejected. This may assist healing of the ruptured ACL. Therefore, this study would support further clinical evaluation of dynamic augmentation of ACL repair.

Preparation and evaluation of 99mTc-EDDA/HYNIC-[Lys 3]-bombesin for imaging gastrin-releasing peptide receptor-positive tumours.

Science.gov (United States)

Ferro-Flores, Guillermina; Arteaga de Murphy, Consuelo; Rodriguez-Cortés, Jeanette; Pedraza-López, Martha; Ramírez-Iglesias, María Teresa

2006-04-01

Bombesin is a peptide that was initially isolated from frog skin and which belongs to a large group of neuropeptides with many biological functions. The human equivalent is gastrin-releasing peptide (GRP), whose receptors are over-expressed in a variety of malignant tumours. To prepare a HYNIC-[Lys 3]-bombesin analogue that could be easily labelled with 99mTc from lyophilized kit formulations and to evaluate its potential as an imaging agent for GRP receptor-positive tumours. HYNIC was conjugated to the epsilon-amino group of Lys 3 residue at the N-terminal region of bombesin via succinimidyl-N-Boc-HYNIC at pH 9.0. 99mTc labelling was performed by addition of sodium pertechnetate solution and 0.2 M phosphate buffer pH 7.0 to a lyophilized formulation. Stability studies were carried out by reversed phase HPLC and ITLC-SG analyses in serum and cysteine solutions. In-vitro internalization was tested using human prostate cancer PC-3 cells with blocked and non-blocked receptors. Biodistribution and tumour uptake were determined in PC-3 tumour-bearing nude mice. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin was obtained with radiochemical purities >93% and high specific activity ( approximately 0.1 GBq.nmol). Results of in-vitro studies demonstrated a high stability in serum and cysteine solutions, specific cell receptor binding and rapid internalization. Biodistribution data showed a rapid blood clearance, with predominantly renal excretion and specific binding towards GRP receptor-positive tissues such as pancreas and PC-3 tumours. 99mTc-EDDA/HYNIC-[Lys 3]-bombesin obtained from lyophilized kit formulations has promising characteristics for the diagnosis of malignant tumours that over-express the GRP receptor.

Protective Effect of Wheat Peptides against Indomethacin-Induced Oxidative Stress in IEC-6 Cells

Directory of Open Access Journals (Sweden)

Hong Yin

2014-01-01

Full Text Available Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-κB(NF-κB-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-κB in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.

Conjugation of cell-penetrating peptides with poly(lactic-co-glycolic acid-polyethylene glycol nanoparticles improves ocular drug delivery

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Vasconcelos A

2015-01-01

Full Text Available Aimee Vasconcelos,1 Estefania Vega,2 Yolanda Pérez,3 María J Gómara,1 María Luisa García,2 Isabel Haro1 1Unit of Synthesis and Biomedical Applications of Peptides, Department of Biomedical Chemistry, Institute for Advanced Chemistry of Catalonia, Consejo Superior de Investigaciones Científicas (IQAC-CSIC, 2Department of Physical Chemistry, Institute of Nanoscience and Nanotechnology, Faculty of Pharmacy, University of Barcelona, 3Nuclear Magnetic Resonance Unit, IQAC-CSIC, Barcelona, Spain Abstract: In this work, a peptide for ocular delivery (POD and human immunodeficiency virus transactivator were conjugated with biodegradable poly(lactic-co-glycolic acid (PGLA–polyethylene glycol (PEG-nanoparticles (NPs in an attempt to improve ocular drug bioavailability. The NPs were prepared by the solvent displacement method following two different pathways. One involved preparation of PLGA NPs followed by PEG and peptide conjugation (PLGA-NPs-PEG-peptide; the other involved self-assembly of PLGA-PEG and the PLGA-PEG-peptide copolymer followed by NP formulation. The conjugation of the PEG and the peptide was confirmed by a colorimetric test and proton nuclear magnetic resonance spectroscopy. Flurbiprofen was used as an example of an anti-inflammatory drug. The physicochemical properties of the resulting NPs (morphology, in vitro release, cell viability, and ocular tolerance were studied. In vivo anti-inflammatory efficacy was assessed in rabbit eyes after topical instillation of sodium arachidonate. Of the formulations developed, the PLGA-PEG-POD NPs were the smaller particles and exhibited greater entrapment efficiency and more sustained release. The positive charge on the surface of these NPs, due to the conjugation with the positively charged peptide, facilitated penetration into the corneal epithelium, resulting in more effective prevention of ocular inflammation. The in vitro toxicity of the NPs developed was very low; no ocular irritation

Detecting peptidic drugs, drug candidates and analogs in sports doping: current status and future directions.

Science.gov (United States)

Thevis, Mario; Thomas, Andreas; Schänzer, Wilhelm

2014-12-01

With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes. Therefore, approaches employing chromatographic-mass spectrometric, electrophoretic, immunological and combined test methods have been required and developed. These allow detecting the misuse of peptidic compounds of lower (such as growth hormone-releasing peptides, ARA-290, TB-500, AOD-9604, CJC-1295, desmopressin, luteinizing hormone-releasing hormones, synacthen, etc.), intermediate (e.g., insulins, IGF-1 and analogs, 'full-length' mechano growth factor, growth hormone, chorionic gonadotropin, erythropoietin, etc.) and higher (e.g., stamulumab) molecular mass with desired specificity and sensitivity. A gap between the technically possible detection and the day-to-day analytical practice, however, still needs to be closed.

Hormonal Responses to Cholinergic Input Are Different in Humans with and without Type 2 Diabetes Mellitus.

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Sara Chowdhury

Full Text Available Peripheral muscarinic acetylcholine receptors regulate insulin and glucagon release in rodents but their importance for similar roles in humans is unclear. Bethanechol, an acetylcholine analogue that does not cross the blood-brain barrier, was used to examine the role of peripheral muscarinic signaling on glucose homeostasis in humans with normal glucose tolerance (NGT; n = 10, impaired glucose tolerance (IGT; n = 11, and type 2 diabetes mellitus (T2DM; n = 9. Subjects received four liquid meal tolerance tests, each with a different dose of oral bethanechol (0, 50, 100, or 150 mg given 60 min before a meal containing acetaminophen. Plasma pancreatic polypeptide (PP, glucose-dependent insulinotropic polypeptide (GIP, glucagon-like peptide-1 (GLP-1, glucose, glucagon, C-peptide, and acetaminophen concentrations were measured. Insulin secretion rates (ISRs were calculated from C-peptide levels. Acetaminophen and PP concentrations were surrogate markers for gastric emptying and cholinergic input to islets. The 150 mg dose of bethanechol increased the PP response 2-fold only in the IGT group, amplified GLP-1 release in the IGT and T2DM groups, and augmented the GIP response only in the NGT group. However, bethanechol did not alter ISRs or plasma glucose, glucagon, or acetaminophen concentrations in any group. Prior studies showed infusion of xenin-25, an intestinal peptide, delays gastric emptying and reduces GLP-1 release but not ISRs when normalized to plasma glucose levels. Analysis of archived plasma samples from this study showed xenin-25 amplified postprandial PP responses ~4-fold in subjects with NGT, IGT, and T2DM. Thus, increasing postprandial cholinergic input to islets augments insulin secretion in mice but not humans.ClinicalTrials.gov NCT01434901.

Identification of novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides from meat proteins using in silico analysis.

Science.gov (United States)

Lafarga, Tomas; O'Connor, Paula; Hayes, Maria

2014-09-01

Angiotensin-I-converting enzyme (ACE-I, EC 3.4.15.1), renin (EC 3.4.23.15), and dipeptidyl peptidase-IV (DPP-IV, EC 3.4.14.5) play key roles in the control of hypertension and the development of type-2 diabetes and other diseases associated with metabolic syndrome. The aim of this work was to utilize known in silico methodologies, peptide databases and software including ProtParam (http://web.expasy.org/protparam/), Basic Local Alignment Tool (BLAST), ExPASy PeptideCutter (http://web.expasy.org/peptide_cutter/) and BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/pl/biopep) to assess the release of potentially bioactive DPP-IV, renin and ACE-I inhibitory peptides from bovine and porcine meat proteins including hemoglobin, collagen and serum albumin. These proteins were chosen as they are found commonly in meat by-products such as bone, blood and low-value meat cuts. In addition, the bioactivities of identified peptides were confirmed using chemical synthesis and in vitro bioassays. The concentration of peptide required to inhibit the activity of ACE-I and DPP-IV by 50% was determined for selected, active peptides. Novel ACE-I and DPP-IV inhibitory peptides were identified in this study using both in silico analysis and a literature search to streamline enzyme selection for peptide production. These novel peptides included the ACE-I inhibitory tri-peptide Ile-Ile-Tyr and the DPP-IV inhibitory tri-peptide Pro-Pro-Leu corresponding to sequences f (182-184) and f (326-328) of both porcine and bovine serum albumin which can be released following hydrolysis with the enzymes papain and pepsin, respectively. This work demonstrates that meat proteins are a suitable resource for the generation of bioactive peptides and further demonstrates the usefulness of in silico methodologies to streamline identification and generation of bioactive peptides. Copyright © 2014 Elsevier Inc. All rights reserved.

Augment-type two stage accelerator

International Nuclear Information System (INIS)

Ogino, Mutsuo; Azuma, Kingo.

1995-01-01

When a flying body accelerated by a gas gun at a first stage enters into an augment rail passing through an introduction tube, an ignition capacitor for initial plasmas is turned ON to apply a voltage between the augment rails. Subsequently, the accelerating gas present behind the flying body is formed into plasmas by a laser, to flow electric current from one of the inner augment rails → plasma armature → the other of the inner augment rails, and additionally accelerate the flying body by Lorentz force formed in this case. Since the plasmas are maintained in a state of higher density than the plasmas obtained by using all of the augment rails, the ignition capacitor for initial plasmas in switched to a power source. As a result, it is possible to flow the maximum current before the plasmas expand, and a large accelerating force and a high magnetic flux density are attained, to improve acceleration performance of the flying body. (N.H.)

2-Dimensional changes of the soft tissue profile of augmented and non-augmented human extraction sockets: a randomized pilot study.

Science.gov (United States)

Flügge, Tabea; Nelson, Katja; Nack, Claudia; Stricker, Andres; Nahles, Susanne

2015-04-01

This study identified the soft tissue changes of the alveolar ridge at different time points within 12 weeks after tooth extraction with and without socket augmentation. In 38 patients with single tooth extractions, 40 sockets were augmented and 39 extraction sockets were not augmented. At 2, 4, 6, 8 and 12 weeks impressions were taken and casts digitized with a laser scanner. The horizontal and vertical changes were compared between augmented and non-augmented sites. A p-value sockets were between 0.4 mm (2 weeks) and 0.8 mm (12 weeks). In non-augmented sockets changes of 0.7 mm (2 weeks) and of 1.0 mm (12 weeks) were demonstrated. The mean values differed significantly between the buccal and oral region (p sockets showed less resorption within 4 weeks after extraction compared to non-augmented sockets. Non-augmented sockets showed a continuous dimensional loss with a great variation over 12 weeks whereas augmented sockets had the highest degree of resorption between 4 and 6 weeks. At 12 weeks a comparable resorption in augmented and non-augmented sockets was observed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic–Pituitary–Gonadal Axis

Directory of Open Access Journals (Sweden)

Takayoshi Ubuka

2018-01-01

Full Text Available Gonadotropin-inhibitory hormone (GnIH is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic–pituitary–gonadal (HPG axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.

Antibody constant region peptides can display immunomodulatory activity through activation of the Dectin-1 signalling pathway.

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Elena Gabrielli

Full Text Available We previously reported that a synthetic peptide with sequence identical to a CDR of a mouse monoclonal antibody specific for difucosyl human blood group A exerted an immunomodulatory activity on murine macrophages. It was therapeutic against systemic candidiasis without possessing direct candidacidal properties. Here we demonstrate that a selected peptide, N10K, putatively deriving from the enzymatic cleavage of the constant region (Fc of human IgG(1, is able to induce IL-6 secretion and pIkB-α activation. More importantly, it causes an up-regulation of Dectin-1 expression. This leads to an increased activation of β-glucan-induced pSyk, CARD9 and pIkB-α, and an increase in the production of pro-inflammatory cytokines such as IL-6, IL-12, IL-1β and TNF-α. The increased activation of this pathway coincides with an augmented phagocytosis of non opsonized Candida albicans cells by monocytes. The findings suggest that some Fc-peptides, potentially deriving from the proteolysis of immunoglobulins, may cause an unexpected immunoregulation in a way reminiscent of innate immunity molecules.

Characterization of antidiabetic and antihypertensive properties of canary seed (Phalaris canariensis L.) peptides.

Science.gov (United States)

Estrada-Salas, Patricia A; Montero-Morán, Gabriela M; Martínez-Cuevas, Pedro P; González, Carmen; Barba de la Rosa, Ana P

2014-01-15

Canary grass is used as traditional food for diabetes and hypertension treatment. The aim of this work is to characterize the biological activity of encrypted peptides released after gastrointestinal digestion of canary seed proteins. Canary peptides showed 43.5% inhibition of dipeptidyl peptidase IV (DPPIV) and 73.5% inhibition of angiotensin-converting enzyme (ACE) activity. An isolated perfused rat heart system was used to evaluate the canary seed vasoactive effect. Nitric oxide (NO), a major vasodilator agent, was evaluated in the venous effluent from isolated perfused rat heart. Canary seed peptides (1 μg/mL) were able to induce the production of NO (12.24 μM) in amounts similar to those induced by captopril (CPT) and bradykinin (BK). These results show that encrypted peptides in canary seed have inhibitory activity against DPPIV and ACE, enzymes that are targets for diabetes and hypertension treatments.

Augmented assessment as a means to augmented reality.

Science.gov (United States)

Bergeron, Bryan

2006-01-01

Rigorous scientific assessment of educational technologies typically lags behind the availability of the technologies by years because of the lack of validated instruments and benchmarks. Even when the appropriate assessment instruments are available, they may not be applied because of time and monetary constraints. Work in augmented reality, instrumented mannequins, serious gaming, and similar promising educational technologies that haven't undergone timely, rigorous evaluation, highlights the need for assessment methodologies that address the limitations of traditional approaches. The most promising augmented assessment solutions incorporate elements of rapid prototyping used in the software industry, simulation-based assessment techniques modeled after methods used in bioinformatics, and object-oriented analysis methods borrowed from object oriented programming.

Nonpeptide and peptide growth hormone secretagogues act both as ghrelin receptor agonist and as positive or negative allosteric modulators of ghrelin signaling

DEFF Research Database (Denmark)

Holst, Birgitte; Brandt, Erik; Bach, Anders

2005-01-01

Two nonpeptide (L692,429 and MK-677) and two peptide [GH-releasing peptide (GHRP)-6 and ghrelin] agonists were compared in binding and in signal transduction assays: calcium mobilization, inositol phosphate turnover, cAMP-responsive element (CRE), and serum-responsive element (SRE) controlled tra...

Gastrin-releasing peptide receptor (GRPr) promotes EMT, growth, and invasion in canine prostate cancer.

Science.gov (United States)

Elshafae, Said M; Hassan, Bardes B; Supsavhad, Wachiraphan; Dirksen, Wessel P; Camiener, Rachael Y; Ding, Haiming; Tweedle, Michael F; Rosol, Thomas J

2016-06-01

The gastrin-releasing peptide receptor (GRPr) is upregulated in early and late-stage human prostate cancer (PCa) and other solid tumors of the mammary gland, lung, head and neck, colon, uterus, ovary, and kidney. However, little is known about its role in prostate cancer. This study examined the effects of a heterologous GRPr agonist, bombesin (BBN), on growth, motility, morphology, gene expression, and tumor phenotype of an osteoblastic canine prostate cancer cell line (Ace-1) in vitro and in vivo. The Ace-1 cells were stably transfected with the human GRPr and tumor cells were grown in vitro and as subcutaneous and intratibial tumors in nude mice. The effect of BBN was measured on cell proliferation, cell migration, tumor growth (using bioluminescence), tumor cell morphology, bone tumor phenotype, and epithelial-mesenchymal transition (EMT) and metastasis gene expression (quantitative RT-PCR). GRPr mRNA expression was measured in primary canine prostate cancers and normal prostate glands. Bombesin (BBN) increased tumor cell proliferation and migration in vitro and tumor growth and invasion in vivo. BBN upregulated epithelial-to-mesenchymal transition (EMT) markers (TWIST, SNAIL, and SLUG mRNA) and downregulated epithelial markers (E-cadherin and β-catenin mRNA), and modified tumor cell morphology to a spindle cell phenotype. Blockade of GRPr upregulated E-cadherin and downregulated VIMENTIN and SNAIL mRNA. BBN altered the in vivo tumor phenotype in bone from an osteoblastic to osteolytic phenotype. Primary canine prostate cancers had increased GRPr mRNA expression compared to normal prostates. These data demonstrated that the GRPr is important in prostate cancer growth and progression and targeting GRPr may be a promising strategy for treatment of prostate cancer. Prostate 76:796-809, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Common and divergent structural features of a series of corticotropin releasing factor-related peptides.

Science.gov (United States)

Grace, Christy Rani R; Perrin, Marilyn H; Cantle, Jeffrey P; Vale, Wylie W; Rivier, Jean E; Riek, Roland

2007-12-26

Members of the corticoliberin family include the corticotropin releasing factors (CRFs), sauvagine, the urotensins, and urocortin 1 (Ucn1), which bind to both the CRF receptors CRF-R1 and CRF-R2, and the urocortins 2 (Ucn2) and 3 (Ucn3), which are selective agonists of CRF-R2. Structure activity relationship studies led to several potent and long-acting analogues with selective binding to either one of the receptors. NMR structures of six ligands of this family (the antagonists astressin B and astressin2-B, the agonists stressin1, and the natural ligands human Ucn1, Ucn2, and Ucn3) were determined in DMSO. These six peptides show differences in binding affinities, receptor-selectivity, and NMR structure. Overall, their backbones are alpha-helical, with a small kink or a turn around residues 25-27, resulting in a helix-loop-helix motif. The C-terminal helices are of amphipathic nature, whereas the N-terminal helices vary in their amphipathicity. The C-terminal helices thereby assume a conformation very similar to that of astressin bound to the ECD1 of CRF-R2 recently reported by our group.1 On the basis of an analysis of the observed 3D structures and relative potencies of [Ala]-substituted analogues, it is proposed that both helices could play a crucial role in receptor binding and selectivity. In conclusion, the C-terminal helices may interact along their hydrophobic faces with the ECD1, whereas the entire N-terminal helical surface may be involved in receptor activation. On the basis of the common and divergent features observed in the 3D structures of these ligands, multiple binding models are proposed that may explain their plurality of actions.

Growth Hormone-Releasing Peptide 6 Enhances the Healing Process and Improves the Esthetic Outcome of the Wounds

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Yssel Mendoza Marí

2016-01-01

Full Text Available In addition to its cytoprotective effects, growth hormone-releasing peptide 6 (GHRP-6 proved to reduce liver fibrotic induration. CD36 as one of the GHRP-6 receptors appears abundantly represented in cutaneous wounds granulation tissue. The healing response in a scenario of CD36 agonistic stimulation had not been previously investigated. Excisional full-thickness wounds (6 mmØ were created in the dorsum of Wistar rats and topically treated twice a day for 5 days. The universal model of rabbit’s ears hypertrophic scars was implemented and the animals were treated daily for 30 days. Treatments for both species were based on a CMC jelly composition containing GHRP-6 400 μg/mL. Wounds response characterization included closure dynamic, RT-PCR transcriptional profile, histology, and histomorphometric procedures. The rats experiment indicated that GHRP-6 pharmacodynamics involves attenuation of immunoinflammatory mediators, their effector cells, and the reduction of the expression of fibrotic cytokines. Importantly, in the hypertrophic scars rabbit’s model, GHRP-6 intervention dramatically reduced the onset of exuberant scars by activating PPARγ and reducing the expression of fibrogenic cytokines. GHRP-6 showed no effect on the reversion of consolidated lesions. This evidence supports the notion that CD36 is an active and pharmacologically approachable receptor to attenuate wound inflammation and accelerate its closure so as to improve wound esthetic.

Bioactive peptides: production, health effects and application as natural supplements for functional foods production

Directory of Open Access Journals (Sweden)

S. Mirdamadi

2017-05-01

Full Text Available Bioactive peptides, are inactive components within the structure of the protein and when they are released by enzymatic hydrolysis, show different physiological functions. Recently, the identification and characterization of bioactive peptides derived from plant and animal sources and different microorganisms is highly regarded. They are produced during enzymatic hydrolysis by gastrointestinal enzymes or enzymes extracted from microorganisms and plants or by proteolytic starter cultures during fermentation process and exhibit different activities including: opioid, mineral binding, immunomodulatory, antioxidant, antimicrobial, anti-inflammatory, chlosterol lowering and so on. Take advantage of bioactive peptides as components of health is related to bio stability assurance, bioavailability and safety of them. The use of computer-based techniques and the use of various databases completed in laboratory studies,  have provided the possibility of studying the mechanisms of action of different peptides.

Renal clearance of the thyrotropin-releasing hormone-like peptide pyroglutamyl-glutamyl-prolineamide in humans

NARCIS (Netherlands)

W. Klootwijk (Willem); E. Sleddens-Linkels (Esther); R.D.H. de Boer (Remco); C.A. Jansen; R. Autar; W.W. de Herder (Wouter); E.R. Boeve; T.J. Visser (Theo); W.J. de Greef

1997-01-01

textabstractTRH-like peptides have been identified that differ from TRH (pGlu-His-ProNH2) in the middle amino acid. We have estimated TRH-like immunoreactivity (TRH-LI) in human serum and urine by RIA with TRH-specific antiserum 8880 or with antiserum 4319, which binds

Augmented Reality Using JavaScript

OpenAIRE

Hailemichael, Aida

2013-01-01

The project goal was to provide a mobile application, for a venue called Kulturhuset Karelia which is located in Tammisaari Finland. In this paper, the concept of Augmented Reality technology is briefly discussed along with the mobile application for the venue. The utilisation of JavaScript for creating Augmented reality content for mobile Augmented reality browser is also demonstrated. The application was created by using Architecht API which is Jacvascript library based on the Wikitude...

The pro-apoptotic action of the peptide hormone Neb-colloostatin on insect haemocytes.

Science.gov (United States)

Czarniewska, E; Mrówczynska, L; Kuczer, M; Rosinski, G

2012-12-15

The gonadoinhibitory peptide hormone Neb-colloostatin was first isolated from ovaries of the flesh fly Neobellieria bullata. This 19-mer peptide is thought to be a cleaved product of a collagen-like precursor molecule that is formed during remodelling of the extracellular matrix. In this study, we report that upon injection of picomolar and nanomolar doses, this peptide exerts a pro-apoptotic action on haemocytes of Tenebrio molitor adults, as visualized by changes in morphology and viability. The F-actin cytoskeleton was found to aggregate into distinctive patches. This may be responsible for the observed inhibition of adhesion of haemocytes and for the stimulation of filopodia formation. However, Neb-colloostatin injection did not induce the formation of autophagic vacuoles. Our results suggest that physiological concentrations of Neb-colloostatin play an important role in controlling the quantity and activity of haemocytes in insect haemolymph. They also suggest that during periods in which Neb-colloostatin is released, this peptide may cause a weakening of the insects' immune system. This is the first report that exposure to a peptide hormone causes apoptosis in insect haemocytes.

Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

Science.gov (United States)

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

2011-06-01

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

Augmented Reality for Multi-disciplinary Collaboration

OpenAIRE

Wang, Xiangyu; Rui,

2010-01-01

This chapter presents a framework for multi-disciplinary collaboration. Tangible Augmented Reality has been raised as one of suitable systems for design collaboration. Furthermore, it emphasizes the advantages of Tangible Augmented Reality to illustrate the needs for integrating the Tangible User Interfaces and Augmented Reality Systems.

Interaction of calcitonin gene related peptide (CGRP) and substance P (SP) in human skin.

Science.gov (United States)

Schlereth, Tanja; Schukraft, Jonas; Krämer-Best, Heidrun H; Geber, Christian; Ackermann, Tatiana; Birklein, Frank

2016-10-01

Calcitonin gene related peptide (CGRP) and substance P (SP) are neuropeptides that are simultaneously released from nociceptive C-fibers. CGRP is a potent vasodilator, inducing a long-lasting increase in superficial skin blood flow, whereas SP induces only a brief vasodilation but a significant plasma extravasation. CGRP and SP may play important roles in the pathophysiology of various pain states but little is known about their interaction. Different concentrations of SP (ranging from 10 -5 M to 10 -9 M) were applied to the volar forearm of 24 healthy subjects via dermal microdialysis. SP was applied either alone or in combination with CGRP10 -9 M and CGRP 10 -6 M. As expected, SP induced a transient increase in skin blood flow that decayed shortly after application. This transient blood flow peak was blunted with co-application of CGRP 10 -9 M and inhibited with co-application of CGRP10 -6 M. SP alone induced plasma protein extravasation (PPE). However, when CGRP10 -6 M was added, the PPE significantly increased. Our results demonstrate a complex interaction of the neuropeptides CGRP and SP. CGRP10 -6 M prevented SP-induced early vasodilation but augmented SP-induced PPE. These interactions might explain why vascular symptoms in chronic pain can differ strikingly between individuals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis

International Nuclear Information System (INIS)

Nair, Baiju G.; Fukuda, Takahiro; Mizuki, Toru; Hanajiri, Tatsuro; Maekawa, Toru

2012-01-01

Highlights: ► We study the intracellular localisation of TAT-SPIONs using 3-D electron tomography. ► 3-D images of TAT-SPIONs in a cell are clearly shown. ► Release of TAT-SPIONs from endocytic vesicles into the cytoplasm is clearly shown. -- Abstract: Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

Cathepsin-Mediated Cleavage of Peptides from Peptide Amphiphiles Leads to Enhanced Intracellular Peptide Accumulation

Energy Technology Data Exchange (ETDEWEB)

Acar, Handan [Institute; Department; Samaeekia, Ravand [Institute; Department; Schnorenberg, Mathew R. [Institute; Department; Medical; Sasmal, Dibyendu K. [Institute; Huang, Jun [Institute; Tirrell, Matthew V. [Institute; Institute; LaBelle, James L. [Department

2017-08-24

Peptides synthesized in the likeness of their native interaction domain(s) are natural choices to target protein protein interactions (PPIs) due to their fidelity of orthostatic contact points between binding partners. Despite therapeutic promise, intracellular delivery of biofunctional peptides at concentrations necessary for efficacy remains a formidable challenge. Peptide amphiphiles (PAs) provide a facile method of intracellular delivery and stabilization of bioactive peptides. PAs consisting of biofunctional peptide headgroups linked to hydrophobic alkyl lipid-like tails prevent peptide hydrolysis and proteolysis in circulation, and PA monomers are internalized via endocytosis. However, endocytotic sequestration and steric hindrance from the lipid tail are two major mechanisms that limit PA efficacy to target intracellular PPIs. To address these problems, we have constructed a PA platform consisting of cathepsin-B cleavable PAs in which a selective p53-based inhibitory peptide is cleaved from its lipid tail within endosomes, allowing for intracellular peptide accumulation and extracellular recycling of the lipid moiety. We monitor for cleavage and follow individual PA components in real time using a resonance energy transfer (FRET)-based tracking system. Using this platform, components in real time using a Forster we provide a better understanding and quantification of cellular internalization, trafficking, and endosomal cleavage of PAs and of the ultimate fates of each component.

Performance of a self-augmented railgun

International Nuclear Information System (INIS)

Burton, R.L.; Witherspoon, F.D.; Goldstein, S.A.

1991-01-01

The accelerating force of a railgun 1/2L'I 2 a can be increased by augmenting the self-induced magnetic field created by the armature current. Augmentation fields can be produced by external current coils or, as is done here, by shorting the railgun muzzle, and using the gun rails as the augmentation coil. Experimental results are presented for a 3.6-m railgun operated in this self-augmented mode, and effective inductance gradients are achieved which are as much as 9.3 times that of the unaugmented gun. A circuit model is presented which explains features of the measured shunt current and voltage. It is concluded that self-augmentation is an effective way to reduce ohmic heating in the armature of a railgun

Receptors for GRP/bombesin-like peptides in the rat forebrain

International Nuclear Information System (INIS)

Wolf, S.S.; Moody, T.W.

1985-01-01

Binding sites in the rat forebrain were characterized using ( 125 I-Tyr4)bombesin as a receptor probe. Pharmacology experiments indicate that gastrin releasing peptide (GRP) and the GRP fragments GRP as well as Ac-GRP inhibited radiolabeled (Tyr4)bombesin binding with high affinity. Biochemistry experiments indicated that heat, N-ethyl maleimide or trypsin greatly reduced radiolabeled (Tyr4)bombesin binding. Also, autoradiographic studies indicated that highest grain densities were present in the stria terminalis, periventricular and suprachiasmatic nucleus of the hypothalamus, dorsomedial and rhomboid thalamus, dentate gyrus, hippocampus and medial amygdaloid nucleus. The data suggest that CNS protein receptors, which are discretely distributed in the rat forebrain, may mediate the action of endogenous GRP/bombesin-like peptides

Protein kinase C involvement in the acetylcholine release reduction induced by amyloid-beta(25-35) aggregates on neuromuscular synapses.

Science.gov (United States)

Tomàs, Marta; Garcia, Neus; Santafé, Manuel M; Lanuza, Maria; Tomàs, Josep

2009-01-01

Using intracellular recording of the diaphragm muscle of adult rats, we have investigated the short-term functional effects of amyloid-beta (Abeta(25-35) peptide aggregates on the modulation of acetylcholine (ACh) release and the involvement of protein kinase C (PKC). The non-aggregated form of this peptide does not change the evoked and spontaneous transmitter release parameters on the neuromuscular synapse. However, the aggregated form of Abeta(25-35) acutely interferes with evoked quantal ACh release (approximately 40% reduction) when synaptic activity in the ex vivo neuromuscular preparation is maintained by low frequency (1 Hz) electrical stimulation. This effect is partially dependent on the activity of PKC that may have a permissive action. The end result of Abeta(25-35) is in opposition to the PKC-dependent maintenance effect on ACh release manifested in active synapses.

INFORMATION VIA AUGMENTED

OpenAIRE

Tetteh, Sampson

2015-01-01

The vast majority of mobile technology today has developed over the past dec-ades. The thirst for information and communication has brought about high data transfer speed on modern mobile handset devices. This makes it possible for Augmented Reality to be used on mobile phones. Vaasa University of Applied Science, Technobothnia science resource center and Lumivaara Museum saw the importance of information and decided to embark on a pilot project where Augmented Reality will not be only us...

Fingerprinting Desmosine-Containing Elastin Peptides

Science.gov (United States)

Schräder, Christoph U.; Heinz, Andrea; Majovsky, Petra; Schmelzer, Christian E. H.

2015-05-01

Elastin is a vital protein of the extracellular matrix of jawed vertebrates and provides elasticity to numerous tissues. It is secreted in the form of its soluble precursor tropoelastin, which is subsequently cross-linked in the course of the elastic fiber assembly. The process involves the formation of the two tetrafunctional amino acids desmosine (DES) and isodesmosine (IDES), which are unique to elastin. The resulting high degree of cross-linking confers remarkable properties, including mechanical integrity, insolubility, and long-term stability to the protein. These characteristics hinder the structural elucidation of mature elastin. However, MS2 data of linear and cross-linked peptides released by proteolysis can provide indirect insights into the structure of elastin. In this study, we performed energy-resolved collision-induced dissociation experiments of DES, IDES, their derivatives, and DES-/IDES-containing peptides to determine characteristic product ions. It was found that all investigated compounds yielded the same product ion clusters at elevated collision energies. Elemental composition determination using the exact masses of these ions revealed molecular formulas of the type CxHyN, suggesting that the pyridinium core of DES/IDES remains intact even at relatively high collision energies. The finding of these specific product ions enabled the development of a similarity-based scoring algorithm that was successfully applied on LC-MS/MS data of bovine elastin digests for the identification of DES-/IDES-cross-linked peptides. This approach facilitates the straightforward investigation of native cross-links in elastin.

Release of a wound-healing agent from PLGA microspheres in a thermosensitive gel.

Science.gov (United States)

Machado, H A; Abercrombie, J J; You, T; Deluca, P P; Leung, K P

2013-01-01

The purpose of this research was to develop a topical microsphere delivery system in a thermosensitive 20% poloxamer 407 gel (Pluronic F127) to control release of KSL-W, a cationic antimicrobial decapeptide, for a period of 4-7 days for potential application in combat related injuries. KSL-W loaded microsphere formulations were prepared by a solvent extraction-evaporation method (water-oil-water), with poly (D,L-lactic-co-glycolic acid) (PLGA) (50 : 50, low-weight, and hydrophilic end) as the polymeric system. After optimization of the process, three formulations (A, B, and C) were prepared with different organic to water ratio of the primary emulsion while maintaining other components and manufacturing parameters constant. Formulations were characterized for surface morphology, porous nature, drug loading, in vitro drug release, and antimicrobial activity. Microspheres containing 20% peptide with porous surfaces and internal structure were prepared in satisfactory yields and in sizes varying from 25 to 50 μm. Gels of 20% Pluronic F127, which were liquid at or below 24.6°C and formed transparent films at body temperature, were used as carriers for the microspheres. Rheological studies showed a gelation temperature of 24.6°C for the 20% Pluronic F127 gel alone. Gelation temperature and viscosity of formulations A, B, and C as a function of temperature were very close to those of the carrier. A Franz diffusion cell system was used to study the release of peptide from the microspheres suspended in both, phosphate-buffered saline (PBS) and a 20% Pluronic F127 gel. In vitro release of greater than 50% peptide was found in all formulations in both PBS and the gel, and in one formulation there was a release of 75% in both PBS and the gel. Fractions collected from the release process were also tested for bactericidal activity against Staphylococcus epidermidis using the broth microdilution method and found to provide effective antimicrobial activity to warrant

The novel protein kinase C epsilon isoform modulates acetylcholine release in the rat neuromuscular junction.

Science.gov (United States)

Obis, Teresa; Hurtado, Erica; Nadal, Laura; Tomàs, Marta; Priego, Mercedes; Simon, Anna; Garcia, Neus; Santafe, Manel M; Lanuza, Maria A; Tomàs, Josep

2015-12-01

Various protein kinase C (PKC) isoforms contribute to the phosphorylating activity that modulates neurotransmitter release. In previous studies we showed that nPKCε is confined in the presynaptic site of the neuromuscular junction and its presynaptic function is activity-dependent. Furthermore, nPKCε regulates phorbol ester-induced acetylcholine release potentiation, which further indicates that nPKCε is involved in neurotransmission. The present study is designed to examine the nPKCε involvement in transmitter release at the neuromuscular junction. We use the specific nPKCε translocation inhibitor peptide εV1-2 and electrophysiological experiments to investigate the involvement of this isoform in acetylcholine release. We observed that nPKCε membrane translocation is key to the synaptic potentiation of NMJ, being involved in several conditions that upregulate PKC isoforms coupling to acetylcholine (ACh) release (incubation with high Ca(2+), stimulation with phorbol esters and protein kinase A, stimulation with adenosine 3',5'-cyclic monophosphorothioate, 8-Bromo-, Rp-isomer, sodium salt -Sp-8-BrcAMP-). In all these conditions, preincubation with the nPKCε translocation inhibitor peptide (εV1-2) impairs PKC coupling to acetylcholine release potentiation. In addition, the inhibition of nPKCε translocation and therefore its activity impedes that presynaptic muscarinic autoreceptors and adenosine autoreceptors modulate transmitter secretion. Together, these results point to the importance of nPKCε isoform in the control of acetylcholine release in the neuromuscular junction.

Augmentation with a reinforced acellular fascia lata strip graft limits cyclic gapping of supraspinatus repairs in a human cadaveric model.

Science.gov (United States)

Milks, Ryan A; Kolmodin, Joel D; Ricchetti, Eric T; Iannotti, Joseph P; Derwin, Kathleen A

2018-06-01

A reinforced biologic strip graft was designed to mechanically augment the repair of rotator cuff tears that are fully reparable by arthroscopic techniques yet have a likelihood of failure. This study assessed the extent to which augmentation of human supraspinatus repairs with a reinforced fascia strip can reduce gap formation during in vitro cyclic loading. The supraspinatus tendon was sharply released from the proximal humerus and repaired back to its insertion with anchors in 9 matched pairs of human cadaveric shoulders. One repair from each pair was also augmented with a reinforced fascia strip. All repairs were subjected to cyclic mechanical loading of 5 to 180 N for 1000 cycles. All augmented and nonaugmented repair constructs completed 1000 cycles of loading. Augmentation with a reinforced fascia strip graft significantly decreased the amount of gap formation compared with nonaugmented repairs. The average gap formation of augmented repairs was 1.5 ± 0.7 mm after the first cycle vs. 3.0 ± 1.2 mm for nonaugmented repairs (P = .003) and 5.0 ± 1.5 mm after 1000 cycles of loading, which averaged 24% ± 21% less than the gap formation of nonaugmented repairs (7.0 ± 2.8 mm, P = .014). Cadaveric human supraspinatus repairs augmented with a reinforced fascia strip have significantly less initial stroke elongation and gap formation than repairs without augmentation. Augmentation limited gap formation to the greatest extent early in the testing protocol. Human studies are necessary to confirm the appropriate indications and effectiveness of augmentation scaffolds for rotator cuff repair healing in the clinical setting. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

An integrated buccal delivery system combining chitosan films impregnated with peptide loaded PEG-b-PLA nanoparticles.

Science.gov (United States)

Giovino, Concetta; Ayensu, Isaac; Tetteh, John; Boateng, Joshua S

2013-12-01

Peptide (insulin) loaded nanoparticles (NPs) have been embedded into buccal chitosan films (Ch-films-NPs). These films were produced by solvent casting and involved incorporating in chitosan gel (1.25% w/v), NPs-Insulin suspensions at three different concentrations (1, 3, and 5mg of NPs per film) using glycerol as plasticiser. Film swelling and mucoadhesion were investigated using 0.01M PBS at 37°C and texture analyzer, respectively. Formulations containing 3mg of NPs per film produced optimised films with excellent mucoadhesion and swelling properties. Dynamic laser scattering measurements showed that the erosion of the chitosan backbone controlled the release of NPs from the films, preceding in vitro drug (insulin) release from Ch-films-NPs after 6h. Modulated release was observed with 70% of encapsulated insulin released after 360h. The use of chitosan films yielded a 1.8-fold enhancement of ex vivo insulin permeation via EpiOral™ buccal tissue construct relative to the pure drug. Flux and apparent permeation coefficient of 0.1μg/cm(2)/h and 4×10(-2)cm(2)/h were respectively obtained for insulin released from Ch-films-NPs-3. Circular dichroism and FTIR spectroscopy demonstrated that the conformational structure of the model peptide drug (insulin) released from Ch-films-NPs was preserved during the formulation process. Copyright © 2013 Elsevier B.V. All rights reserved.

INTEGRATIVE AUGMENTATION OF STANDARDIZED MANAGEMENT SYSTEMS

Directory of Open Access Journals (Sweden)

Stanislav Karapetrovic

2008-03-01

Full Text Available The development, features and integrating abilities of different international standards related to management systems are discussed. A group of such standards that augment the performance of quality management systems in organizations is specifically focused on. The concept, characteristics and an illustrative example of one augmenting standard, namely ISO 10001, are addressed. Integration of standardized augmenting systems, both by themselves and within the overall management system, is examined. It is argued that, in research and practice alike, integrative augmentation represents the future of standardized quality and other management systems.

Modulation of taste responsiveness by the satiation hormone peptide YY

Science.gov (United States)

La Sala, Michael S.; Hurtado, Maria D.; Brown, Alicia R.; Bohórquez, Diego V.; Liddle, Rodger A.; Herzog, Herbert; Zolotukhin, Sergei; Dotson, Cedrick D.

2013-01-01

It has been hypothesized that the peripheral taste system may be modulated in the context of an animal's metabolic state. One purported mechanism for this phenomenon is that circulating gastrointestinal peptides modulate the functioning of the peripheral gustatory system. Recent evidence suggests endocrine signaling in the oral cavity can influence food intake (FI) and satiety. We hypothesized that these hormones may be affecting FI by influencing taste perception. We used immunohistochemistry along with genetic knockout models and the specific reconstitution of peptide YY (PYY) in saliva using gene therapy protocols to identify a role for PYY signaling in taste. We show that PYY is expressed in subsets of taste cells in murine taste buds. We also show, using brief-access testing with PYY knockouts, that PYY signaling modulates responsiveness to bitter-tasting stimuli, as well as to lipid emulsions. We show that salivary PYY augmentation, via viral vector therapy, rescues behavioral responsiveness to a lipid emulsion but not to bitter stimuli and that this response is likely mediated via activation of Y2 receptors localized apically in taste cells. Our findings suggest distinct functions for PYY produced locally in taste cells vs. that circulating systemically.—La Sala, M. S., Hurtado, M. D., Brown, A. R., Bohórquez, D. V., Liddle, R. A., Herzog, H., Zolotukhin, S., Dotson, C. D. Modulation of taste responsiveness by the satiation hormone peptide YY. PMID:24043261

Thiomers: potential excipients for non-invasive peptide delivery systems.

Science.gov (United States)

Bernkop-Schnürch, Andreas; Krauland, Alexander H; Leitner, Verena M; Palmberger, Thomas

2004-09-01

In recent years thiolated polymers or so-called thiomers have appeared as a promising alternative in the arena of non-invasive peptide delivery. Thiomers are generated by the immobilisation of thiol-bearing ligands to mucoadhesive polymeric excipients. By formation of disulfide bonds with mucus glycoproteins, the mucoadhesive properties of these polymers are improved up to 130-fold. Due to formation of inter- and intramolecular disulfide bonds within the thiomer itself, dosage forms such as tablets or microparticles display strong cohesive properties resulting in comparatively higher stability, prolonged disintegration times and a more controlled release of the embedded peptide drug. The permeation of peptide drugs through mucosa can be improved by the use of thiolated polymers. Additionally some thiomers exhibit improved inhibitory properties towards peptidases. The efficacy of thiomers in non-invasive peptide delivery could be demonstrated by various in vivo studies. Tablets comprising a thiomer and pegylated insulin, for instance, resulted in a pharmacological efficacy of 7% after oral application to diabetic mice. Furthermore, a pharmacological efficacy of 1.3% was achieved in rats by oral administration of calcitonin tablets comprising a thiomer. Human growth hormone in a thiomer-gel was applied nasally to rats and led to a bioavailability of 2.75%. In all these studies, formulations comprising the corresponding unmodified polymer had only a marginal or no effect. According to these results drug carrier systems based on thiomers seem to be a promising tool for non-invasive peptide drug delivery.

Potent inhibition of late stages of hepadnavirus replication by a modified cell penetrating peptide

DEFF Research Database (Denmark)

Abdul, Fabien; Ndeboko, Bénédicte; Buronfosse, Thierry

2012-01-01

Cationic cell-penetrating peptides (CPPs) and their lipid domain-conjugates (CatLip) are agents for the delivery of (uncharged) biologically active molecules into the cell. Using infection and transfection assays we surprisingly discovered that CatLip peptides were able to inhibit replication...... by confocal laser scanning microscopy indicating severe structural changes of preS/S. Sucrose gradient analysis of supernatants from Deca-(Arg)8-treated cells showed unaffected naked viral nucleocapsids release, which was concomitant with a complete arrest of virion and surface protein-containing subviral...

AUGMENTATION-RELATED BRAIN PLASTICITY

Directory of Open Access Journals (Sweden)

Giovanni eDi Pino

2014-06-01

Full Text Available Today, the anthropomorphism of the tools and the development of neural interfaces require reconsidering the concept of human-tools interaction in the framework of human augmentation. This review analyzes the plastic process that the brain undergoes when it comes into contact with augmenting artificial sensors and effectors and, on the other hand, the changes that the use of external augmenting devices produces in the brain.Hitherto, few studies investigated the neural correlates of augmentation, but clues on it can be borrowed from logically-related paradigms: sensorimotor training, cognitive enhancement, cross-modal plasticity, sensorimotor functional substitution, use and embodiment of tools.Augmentation modifies function and structure of a number of areas, i.e. primary sensory cortices shape their receptive fields to become sensitive to novel inputs. Motor areas adapt the neuroprosthesis representation firing-rate to refine kinematics. As for normal motor outputs, the learning process recruits motor and premotor cortices and the acquisition of proficiency decreases attentional recruitment, focuses the activity on sensorimotor areas and increases the basal ganglia drive on the cortex. Augmentation deeply relies on the frontoparietal network. In particular, premotor cortex is involved in learning the control of an external effector and owns the tool motor representation, while the intraparietal sulcus extracts its visual features. In these areas, multisensory integration neurons enlarge their receptive fields to embody supernumerary limbs. For operating an anthropomorphic neuroprosthesis, the mirror system is required to understand the meaning of the action, the cerebellum for the formation of its internal model and the insula for its interoception. In conclusion, anthropomorphic sensorized devices can provide the critical sensory afferences to evolve the exploitation of tools through their embodiment, reshaping the body representation and the

Confronting an Augmented Reality

Science.gov (United States)

Munnerley, Danny; Bacon, Matt; Wilson, Anna; Steele, James; Hedberg, John; Fitzgerald, Robert

2012-01-01

How can educators make use of augmented reality technologies and practices to enhance learning and why would we want to embrace such technologies anyway? How can an augmented reality help a learner confront, interpret and ultimately comprehend reality itself ? In this article, we seek to initiate a discussion that focuses on these questions, and…

Advanced Intellect-Augmentation Techniques.

Science.gov (United States)

Engelbart, D. C.

This progress report covers a two-year project which is part of a program that is exploring the value of computer aids in augmenting human intellectual capability. The background and nature of the program, its resources, and the activities it has undertaken are outlined. User experience in applying augmentation tools and techniques to various…

Novel Augmentation Strategies in Major Depression

DEFF Research Database (Denmark)

Martiny, Klaus

2017-01-01

Hypothesis The hypotheses of all the four included studies share the common idea that it is possible to augment the effect of antidepressant drug treatment by applying different interventions and with each intervention attain a clinically meaningful better effect compared to a control condition...... and randomised to augmentation with either active or placebo matching pindolol tablets. In the PEMF study patients were continued on ongoing medication and randomised to augmentation with active or inactive (sham) 30 minutes daily PEMF treatment on weekdays. In the Chronos study all patients were treated...... The results from the Pindolol study showed that pindolol did not augment the effect of venlafaxine for the whole sample. However, for those patients classified as slow metabolizers, based on their O-desmethylvenlafaxine/venlafaxine ratio (ODV/V), pindolol did augment the antidepressant effect. For patients...

Augmented Reality for Science Education

DEFF Research Database (Denmark)

Brandt, Harald; Nielsen, Birgitte Lund; Georgsen, Marianne

Augmented reality (AR) holds great promise as a learning tool. So far, however, most research has looked at the technology itself – and AR has been used primarily for commercial purposes. As a learning tool, AR supports an inquiry-based approach to science education with a high level of student...... involvement. The AR-sci-project (Augmented Reality for SCIence education) addresses the issue of applying augmented reality in developing innovative science education and enhancing the quality of science teaching and learning....

Expression and hypophysiotropic actions of corticotropin-releasing factor in Xenopus laevis.

Science.gov (United States)

Boorse, Graham C; Denver, Robert J

2004-07-01

Members of the corticotropin-releasing factor (CRF) family of peptides play pivotal roles in the regulation of neuroendocrine, autonomic, and behavioral responses to physical and emotional stress. In amphibian tadpoles, CRF-like peptides stimulate both thyroid and interrenal (adrenal) hormone secretion, and can thereby modulate the rate of metamorphosis. To better understand the regulation of expression and actions of CRF in amphibians we developed a homologous radioimmunoassay (RIA) for Xenopus laevis CRF (xCRF). We validated this RIA and tissue extraction procedure for the measurement of brain CRF content in tadpoles and juveniles. We show that the CRF-binding protein, which is highly expressed in X. laevis brain, is largely removed by acid extraction and does not interfere in the RIA. We analyzed CRF peptide content in five microdissected brain regions in prometamorphic tadpoles and juveniles. CRF was detected throughout the brain, consistent with its role as both a hypophysiotropin and a neurotransmitter/neuromodulator. CRF content was highest in the region of the preoptic area (POa) and increased in all brain regions after metamorphosis. Exposure to 4h of handling/shaking stress resulted in increased CRF peptide content in the POa in juvenile frogs. Injections of xCRF into prometamorphic tadpoles increased whole body corticosterone and thyroxine content, thus supporting findings in other anuran species that this peptide functions as both a corticotropin- and a thyrotropin (TSH)-releasing factor. Furthermore, treatment of cultured tadpole pituitaries with xCRF (100nM for 24h) resulted in increased medium content, but decreased pituitary content of TSHbeta-immunoreactivity. Our results support the view that CRF functions as a stress neuropeptide in X. laevis as in other vertebrates. Furthermore, we provide evidence for a dual hypophysiotropic action of CRF on the thyroid and interrenal axes in X. laevis as has been shown previously in other amphibian species.

Augmented Reality on Android

OpenAIRE

Chunghan Li; Chang-Shyh Peng; Daisy F. Sang

2013-01-01

Augmented Reality is an application which combines a live view of real-world environment and computer-generated images. This paper studies and demonstrates an efficient Augmented Reality development in the mobile Android environment with the native Java language and Android SDK. Major components include Barcode Reader, File Loader, Marker Detector, Transform Matrix Generator, and a cloud database.

Augmenting Locomotion in an Anthropomorphic System

Directory of Open Access Journals (Sweden)

Derek Wight

2005-02-01

Full Text Available A powered orthosis has applications ranging from assisting the elderly to augmenting astronauts. An assistive control scheme is developed that uses the force from a slave actuator to augment the force of a master actuator. This can be used to augment a closed-loop control scheme applied to the master actuator. Initially, actuator augmentation is explored both theoretically and experimentally using a simple mechanical system. The control scheme is then applied to a scale model of human lower limbs on a stationary bicycle to investigate the feasibility of a powered orthosis using pneumatic muscle actuators.

The role of imaging in pediatric bladder augmentation

Energy Technology Data Exchange (ETDEWEB)

Breen, Micheal; Chow, Jeanne S. [Boston Children' s Hospital, Department of Radiology, Boston, MA (United States); Phelps, Andrew [UCSF Benioff Children' s Hospital San Francisco, Department of Radiology and Biomedical Imaging, San Francisco, CA (United States); Estrada, Carlos [Boston Children' s Hospital, Department of Urology, Boston, MA (United States)

2015-09-15

Bladder augmentation (also called augmentation cystoplasty) refers to a number of surgical methods that increase the capacity and compliance of the urinary bladder. Imaging has an important role in the postoperative evaluation of bladder augmentation. The most common augmentation procedures utilize enteric segments to augment the bladder. The various types of bladder augmentation have characteristic appearances on different imaging modalities. Spontaneous bladder perforation is a complication that is seen in both early and late post-operative periods and it is one of the most important complications for radiologists to be aware of as it is life-threatening. We review the indications for bladder augmentation in children, the surgical techniques employed, the normal postoperative appearances on imaging studies and the role of imaging complications of bladder augmentation including delayed spontaneous bladder rupture, which is life-threatening. (orig.)

Repeated vertebral augmentation for new vertebral compression fractures of postvertebral augmentation patients: a nationwide cohort study

Directory of Open Access Journals (Sweden)

Liang CL

2015-03-01

Full Text Available Cheng-Loong Liang,1 Hao-Kwan Wang,1 Fei-Kai Syu,2 Kuo-Wei Wang,1 Kang Lu,1 Po-Chou Liliang1 1Department of Neurosurgery, E-Da Hospital, I-Shou University, Kaohsiung City, Taiwan; 2Department of Pharmacy, China Medical University Hospital, Taichung City, Taiwan Purpose: Postvertebral augmentation vertebral compression fractures are common; repeated vertebral augmentation is usually performed for prompt pain relief. This study aimed to evaluate the incidence and risk factors of repeat vertebral augmentation.Methods: We performed a retrospective, nationwide, population-based longitudinal observation study, using the National Health Insurance Research Database (NHIRD of Taiwan. All patients who received vertebral augmentation for vertebral compression fractures were evaluated. The collected data included patient characteristics (demographics, comorbidities, and medication exposure and repeat vertebral augmentation. Kaplan–Meier and stratified Cox proportional hazard regressions were performed for analyses.Results: The overall incidence of repeat vertebral augmentation was 11.3% during the follow-up until 2010. Patients with the following characteristics were at greater risk for repeat vertebral augmentation: female sex (AOR=1.24; 95% confidence interval [CI]: 1.10–2.36, advanced age (AOR=1.60; 95% CI: 1.32–2.08, diabetes mellitus (AOR=4.31; 95% CI: 4.05–5.88, cerebrovascular disease (AOR=4.09; 95% CI: 3.44–5.76, dementia (AOR=1.97; 95% CI: 1.69–2.33, blindness or low vision (AOR=3.72; 95% CI: 2.32–3.95, hypertension (AOR=2.58; 95% CI: 2.35–3.47, and hyperlipidemia (AOR=2.09; 95% CI: 1.67–2.22. Patients taking calcium/ vitamin D (AOR=2.98; 95% CI: 1.83–3.93, bisphosphonates (AOR=2.11; 95% CI: 1.26–2.61, or calcitonin (AOR=4.59; 95% CI: 3.40–5.77 were less likely to undergo repeat vertebral augmentation; however, those taking steroids (AOR=7.28; 95% CI: 6.32–8.08, acetaminophen (AOR=3.54; 95% CI: 2.75–4.83, or nonsteroidal

LC-MS/MS Peptide Mapping with Automated Data Processing for Routine Profiling of N-Glycans in Immunoglobulins

Science.gov (United States)

Shah, Bhavana; Jiang, Xinzhao Grace; Chen, Louise; Zhang, Zhongqi

2014-06-01

Protein N-Glycan analysis is traditionally performed by high pH anion exchange chromatography (HPAEC), reversed phase liquid chromatography (RPLC), or hydrophilic interaction liquid chromatography (HILIC) on fluorescence-labeled glycans enzymatically released from the glycoprotein. These methods require time-consuming sample preparations and do not provide site-specific glycosylation information. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) peptide mapping is frequently used for protein structural characterization and, as a bonus, can potentially provide glycan profile on each individual glycosylation site. In this work, a recently developed glycopeptide fragmentation model was used for automated identification, based on their MS/MS, of N-glycopeptides from proteolytic digestion of monoclonal antibodies (mAbs). Experimental conditions were optimized to achieve accurate profiling of glycoforms. Glycan profiles obtained from LC-MS/MS peptide mapping were compared with those obtained from HPAEC, RPLC, and HILIC analyses of released glycans for several mAb molecules. Accuracy, reproducibility, and linearity of the LC-MS/MS peptide mapping method for glycan profiling were evaluated. The LC-MS/MS peptide mapping method with fully automated data analysis requires less sample preparation, provides site-specific information, and may serve as an alternative method for routine profiling of N-glycans on immunoglobulins as well as other glycoproteins with simple N-glycans.

Hybrid-augmented intelligence:collaboration and cognition

Institute of Scientific and Technical Information of China (English)

Nan-ning ZHENG; Zi-yi LIU; Peng-ju REN; Yong-qiang MA; Shi-tao CHEN; Si-yu YU; Jian-ru XUE

2017-01-01

The long-term goal of artificial intelligence (AI) is to make machines learn and think like human beings. Due to the high levels of uncertainty and vulnerability in human life and the open-ended nature of problems that humans are facing, no matter how intelligent machines are, they are unable to completely replace humans. Therefore, it is necessary to introduce human cognitive capabilities or human-like cognitive models into AI systems to develop a new form of AI, that is, hybrid-augmented intelligence. This form of AI or machine intelligence is a feasible and important developing model. Hybrid-augmented intelligence can be divided into two basic models:one is human-in-the-loop augmented intelligence with human-computer collaboration, and the other is cognitive computing based augmented intelligence, in which a cognitive model is embedded in the machine learning system. This survey describes a basic framework for human-computer collaborative hybrid-augmented intelligence, and the basic elements of hybrid-augmented intelligence based on cognitive computing. These elements include intuitive reasoning, causal models, evolution of memory and knowledge, especially the role and basic principles of intuitive reasoning for complex problem solving, and the cognitive learning framework for visual scene understanding based on memory and reasoning. Several typical applications of hybrid-augmented intelligence in related fields are given.

ARSC: Augmented Reality Student Card--An Augmented Reality Solution for the Education Field

Science.gov (United States)

El Sayed, Neven A. M.; Zayed, Hala H.; Sharawy, Mohamed I.

2011-01-01

Augmented Reality (AR) is the technology of adding virtual objects to real scenes through enabling the addition of missing information in real life. As the lack of resources is a problem that can be solved through AR, this paper presents and explains the usage of AR technology we introduce Augmented Reality Student Card (ARSC) as an application of…

Skin peptide tyrosine-tyrosine, a member of the pancreatic polypeptide family: isolation, structure, synthesis, and endocrine activity.

Science.gov (United States)

Mor, A; Chartrel, N; Vaudry, H; Nicolas, P

1994-10-25

Pancreatic polypeptide, peptide tyrosine-tyrosine (PYY), and neuropeptide tyrosine (NPY), three members of a family of structurally related peptides, are mainly expressed in the endocrine pancreas, in endocrine cells of the gut, and in the brain, respectively. In the present study, we have isolated a peptide of the pancreatic polypeptide family from the skin of the South American arboreal frog Phyllomedusa bicolor. The primary structure of the peptide was established as Tyr-Pro-Pro-Lys-Pro-Glu-Ser-Pro-Gly-Glu10-Asp-Ala-Ser-Pro-Glu-Glu- Met-Asn- Lys-Tyr20-Leu-Thr-Ala-Leu-Arg-His-Tyr-Ile-Asn-Leu30-Val-Thr- Arg-Gln-Arg-Tyr-NH2 . This unusual peptide, named skin peptide tyrosine-tyrosine (SPYY), exhibits 94% similarity with PYY from the frog Rana ridibunda. A synthetic replicate of SPYY inhibits melanotropin release from perifused frog neurointermediate lobes in very much the same way as NPY. These results demonstrate the occurrence of a PYY-like peptide in frog skin. Our data also suggest the existence of a pituitary-skin regulatory loop in amphibians.

Mersiline mesh in premaxillary augmentation.

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Foda, Hossam M T

2005-01-01

Premaxillary retrusion may distort the aesthetic appearance of the columella, lip, and nasal tip. This defect is characteristically seen in, but not limited to, patients with cleft lip nasal deformity. This study investigated 60 patients presenting with premaxillary deficiencies in which Mersiline mesh was used to augment the premaxilla. All the cases had surgery using the external rhinoplasty technique. Two methods of augmentation with Mersiline mesh were used: the Mersiline roll technique, for the cases with central symmetric deficiencies, and the Mersiline packing technique, for the cases with asymmetric deficiencies. Premaxillary augmentation with Mersiline mesh proved to be simple technically, easy to perform, and not associated with any complications. Periodic follow-up evaluation for a mean period of 32 months (range, 12-98 months) showed that an adequate degree of premaxillary augmentation was maintained with no clinically detectable resorption of the mesh implant.

Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

Directory of Open Access Journals (Sweden)

Abimael González-Hernández

2016-01-01

Full Text Available Calcitonin gene-related peptide (CGRP is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP, the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor. This receptor is an atypical G-protein coupled receptor (GPCR composed of three functional proteins: (i the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein, (ii the activity-modifying protein type 1 (RAMP1, and (iii a receptor component protein (RCP. Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia. The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

Identification of a peptide binding protein that plays a role in antigen presentation

International Nuclear Information System (INIS)

Lakey, E.K.; Margoliash, E.; Pierce, S.K.

1987-01-01

The helper T-cell response to globular proteins appears, in general, to require intracellular processing of the antigen, such that a peptide fragment containing the T-cell antigenic determinant is released and transported to and held on the surface of an Ia-expressing, antigen-presenting cell. However, the molecular details underlying these phenomena are largely unknown. The means by which antigenic peptides are anchored on the antigen-presenting cell surface was investigated. A cell surface protein is identified that was isolated by it ability to bind to a 24-amino acid peptide fragment of pigeon cytochrome c, residues 81-104, containing the major antigenic determinant for B10.A mouse T cells. This peptide binding protein, purified from [ 35 S]methionine-labeled cells, appears as two discrete bands of ≅72 and 74 kDa after NaDodSO 4 /PAGE. The protein can be eluted from the peptide affinity column with equivalent concentrations of either the antigenic pigeon cytochrome c peptide or the corresponding nonantigenic peptide of mouse cytochrome c. However, it does not bind to the native cytochromes c, either of pigeon or mouse, and thus the protein appears to recognize some structure available only in the free peptides. This protein plays a role in antigen presentation. Its expression is not major histocompatibility complex-restricted in that the blocking activity of the antisera can be absorbed on spleen cells from mice of different haplotypes. This peptide binding protein can be isolated from a variety of cell types, including B cells, T cells, and fibroblasts. The anchoring of processed peptides on the cell surface by such a protein may play a role in antigen presentation

Augmented Reality-Guided Lumbar Facet Joint Injections.

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Agten, Christoph A; Dennler, Cyrill; Rosskopf, Andrea B; Jaberg, Laurenz; Pfirrmann, Christian W A; Farshad, Mazda

2018-05-08

The aim of this study was to assess feasibility and accuracy of augmented reality-guided lumbar facet joint injections. A spine phantom completely embedded in hardened opaque agar with 3 ring markers was built. A 3-dimensional model of the phantom was uploaded to an augmented reality headset (Microsoft HoloLens). Two radiologists independently performed 20 augmented reality-guided and 20 computed tomography (CT)-guided facet joint injections each: for each augmented reality-guided injection, the hologram was manually aligned with the phantom container using the ring markers. The radiologists targeted the virtual facet joint and tried to place the needle tip in the holographic joint space. Computed tomography was performed after each needle placement to document final needle tip position. Time needed from grabbing the needle to final needle placement was measured for each simulated injection. An independent radiologist rated images of all needle placements in a randomized order blinded to modality (augmented reality vs CT) and performer as perfect, acceptable, incorrect, or unsafe. Accuracy and time to place needles were compared between augmented reality-guided and CT-guided facet joint injections. In total, 39/40 (97.5%) of augmented reality-guided needle placements were either perfect or acceptable compared with 40/40 (100%) CT-guided needle placements (P = 0.5). One augmented reality-guided injection missed the facet joint space by 2 mm. No unsafe needle placements occurred. Time to final needle placement was substantially faster with augmented reality guidance (mean 14 ± 6 seconds vs 39 ± 15 seconds, P Augmented reality-guided facet joint injections are feasible and accurate without potentially harmful needle placement in an experimental setting.

Peptide array-based interaction assay of solid-bound peptides and anchorage-dependant cells and its effectiveness in cell-adhesive peptide design.

Science.gov (United States)

Kato, Ryuji; Kaga, Chiaki; Kunimatsu, Mitoshi; Kobayashi, Takeshi; Honda, Hiroyuki

2006-06-01

Peptide array, the designable peptide library covalently synthesized on cellulose support, was applied to assay peptide-cell interaction, between solid-bound peptides and anchorage-dependant cells, to study objective peptide design. As a model case, cell-adhesive peptides that could enhance cell growth as tissue engineering scaffold material, was studied. On the peptide array, the relative cell-adhesion ratio of NIH/3T3 cells was 2.5-fold higher on the RGDS (Arg-Gly-Asp-Ser) peptide spot as compared to the spot with no peptide, thus indicating integrin-mediated peptide-cell interaction. Such strong cell adhesion mediated by the RGDS peptide was easily disrupted by single residue substitution on the peptide array, thus indicating that the sequence recognition accuracy of cells was strictly conserved in our optimized scheme. The observed cellular morphological extension with active actin stress-fiber on the RGD motif-containing peptide supported our strategy that peptide array-based interaction assay of solid-bound peptide and anchorage-dependant cells (PIASPAC) could provide quantitative data on biological peptide-cell interaction. The analysis of 180 peptides obtained from fibronectin type III domain (no. 1447-1629) yielded 18 novel cell-adhesive peptides without the RGD motif. Taken together with the novel candidates, representative rules of ineffective amino acid usage were obtained from non-effective candidate sequences for the effective designing of cell-adhesive peptides. On comparing the amino acid usage of the top 20 and last 20 peptides from the 180 peptides, the following four brief design rules were indicated: (i) Arg or Lys of positively charged amino acids (except His) could enhance cell adhesion, (ii) small hydrophilic amino acids are favored in cell-adhesion peptides, (iii) negatively charged amino acids and small amino acids (except Gly) could reduce cell adhesion, and (iv) Cys and Met could be excluded from the sequence combination since they have