| 1. |
- Björn, Camilla, et al.
(författare)
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Anti-infective efficacy of the lactoferrin-derived antimicrobial peptide HLR1r
- 2016
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 81, s. 21-28
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial peptides (AMPs) have emerged as a new class of drug candidates for the treatment of infectious diseases. Here we describe a novel AMP, HLR1r, which is structurally derived from the human milk protein lactoferrin and demonstrates a broad spectrum microbicidal action in vitro. The minimum concentration of HLR1r needed for killing >= 99% of microorganisms in vitro, was in the range of 3-50 mu g/ml for common Gram-negative and Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and for the yeast Candida albicans, when assessed in diluted brain-heart infusion medium. We found that HLR1r also possesses anti-inflammatory properties as evidenced by inhibition of tumor necrosis factor alpha (TNF-alpha) secretion from human monocyte-derived macrophages and by repression of interleukin-6 (IL-6) and plasminogen activator inhibitor-1 (PAI-1) secretion from human mesothelial cells, without any cytotoxic effect observed at the concentration range tested (up to 400 mu g/ml). HLR1r demonstrated pronounced anti-infectious effect in in vivo experimental models of cutaneous candidiasis in mice and of excision wounds infected with MRSA in rats as well as in an ex vivo model of pig skin infected with S. aureus. In conclusion, HLR1r may constitute a new therapeutic alternative for local treatment of skin infections. (C) 2016 Elsevier Inc. All rights reserved.
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| 2. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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Nitric oxide inhibition by L-NAME but not 7-NI induces a transient increase in cortical cerebral blood flow and affects the cerebrovasodilation induced by TRH
- 2003
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 24:4, s. 579-583
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Tidskriftsartikel (refereegranskat)abstract
- The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiological effects. One of these is the cerebrovasodilating effect, which has been described under several different conditions. The final mechanism for this effect is unknown. In the present study, we found an initial atropine-resistant cerebral vasodilation (24%) elicited by the NOS inhibitor L-NAME in the rat. D-NAME and 7-NI did not produce this effect. TRH (300 microg kg(-1), i.v.) induced an increase in cerebral blood flow by 62%. L-NAME reduced this effect significantly. The cerebrovasodilating mechanism of TRH, at least in part, is endothelial NO dependent as the neuronal 7-NI NOS inhibitor does not affect the TRH response.
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| 3. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.
- 1998
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 19:10, s. 1675-1677
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Tidskriftsartikel (refereegranskat)abstract
- The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.
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| 4. |
- Larsson, Jan, et al.
(författare)
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Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.
- 1996
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 17:2, s. 293-297
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Tidskriftsartikel (refereegranskat)abstract
- The effects of IV TRH pretreatment on induction of anesthesia with propofol or pentobarbital were investigated in rats. The effects of IV TRH, administered after induction, on duration of propofol anesthesia and the interaction with atropine were also studied. The doses of propofol or pentobarbital were not influenced by TRH. TRH reduced duration of anesthesia after propofol, with higher brain concentrations of propofol at recovery. Atropine did not block this effect, but given alone prolonged duration of anesthesia. It is concluded that TRH shortens the duration of propofol anesthesia, probably due to a pharmacodynamic effect and not to a pharmacokinetic interaction.
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| 5. |
- Magnusson, B. M., et al.
(författare)
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Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH
- 2001
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 22:1, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Besides its well known endocrinological effects, thyrotropin-releasing hormone (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the presence of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terpene on the transdermal penetration of the peptides across full-thickness rat skin were studied. Steady-state permeability values for TRH and M-TRH were 8.7 +/- 2.2 and 6.7 +/- 1.4 microg/cm(2) h, respectively. The addition of 3 % terpene in combination with 47 % ethanol increased the penetration of TRH and M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 microg/cm(2) h, respectively. Rats were studied in vivo for release of thyroid-stimulating hormone (TSH) as a biologic effect after transdermally delivered peptide. Topical application of TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/- 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respectively. It is concluded that, in the rat, peptides can be absorbed through the skin with retained biologic activity, and in amounts sufficient to elicit a physiological response.
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| 6. |
- Andersson, Amelie, et al.
(författare)
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Expression and motor effects of secretin in small and large intestine of the rat
- 2000
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781. ; 21:11, s. 94-1687
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Tidskriftsartikel (refereegranskat)abstract
- Immunocytochemistry and in situ hybridization revealed abundant secretin expressing cells on duodenal villi with a gradual decrease throughout the small intestines of the rat. They were absent in pancreas, stomach and colon. Secretin caused relaxation of rat intestinal longitudinal muscle in vitro. Studies on colon revealed that the secretin-evoked response was unaffected by apamin, tetrodotoxin, L-NAME, VIP or PACAP pretreatment; secretin itself caused desensitization. Addition of VIP or PACAP when the secretin-evoked relaxation was maximal evoked a further relaxation suggesting the presence of distinct receptors. Secretin causes relaxation via activation of secretin receptors located on the smooth muscle and not via any of the related VIP/PACAP receptors.
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| 7. |
- Dahl, Sara, et al.
(författare)
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The host defense peptide LL-37 triggers release of nucleic acids from human mast cells
- 2018
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 109, s. 39-45
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Tidskriftsartikel (refereegranskat)abstract
- The human host defense peptide LL-37 possesses antimicrobial activity but also affects host cell function and viability. Mast cells are involved in innate immunity but no data have been presented on effects of LL-37 on human mast cell viability and export of nucleic acids. Here, we demonstrated by immunofluorescence microscopy that synthesized LL-37 was internalized by human LAD2 mast cells and detected both in cytoplasm and nucleus. Treatment with high (4 and 10 μM) but not low (1 μM) concentrations of LL-37 for 4 h reduced cell viability assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Stimulation with 10 μM LL-37 for 4 h enhanced export of nucleic acids, total protein and lactate dehydrogenase (LDH), suggesting that both nuclear and plasma membranes are permeabilized by LL-37. Although LL-37 triggered release of nucleic acids, no extracellular trap-like structures were observed by laser scanning confocal microscopy of cells incubated with the plasma membrane impermeable nucleic acid fluorophore SYTOX-Green, indicating that LL-37 promotes export of nucleic acids but not formation of extracellular traps. On the other hand, phorbol-12-myristate-13-acetate (PMA), which is a well-known inducer of extracellular traps, stimulated export of nucleic acids and also formation of extracellular trap-like structures. However, PMA had no effect on export of either total protein or LDH. Hence, LL-37 and PMA seem to stimulate export of nucleic acids from LAD2 mast cells through different pathways. In conclusion, we demonstrate that LL-37 triggers release of nucleic acids from human mast cells but not the formation of extracellular trap-like structures.
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| 8. |
- Ghazal, Ahmad, et al.
(författare)
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Venomous gland transcriptome and venom proteomic analysis of the scorpion Androctonus amoreuxi reveal new peptides with anti-SARS-CoV-2 activity
- 2024
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 173
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Tidskriftsartikel (refereegranskat)abstract
- The recent COVID-19 pandemic shows the critical need for novel broad spectrum antiviral agents. Scorpion venoms are known to contain highly bioactive peptides, several of which have demonstrated strong antiviral activity against a range of viruses. We have generated the first annotated reference transcriptome for the Androctonus amoreuxi venom gland and used high performance liquid chromatography, transcriptome mining, circular dichroism and mass spectrometric analysis to purify and characterize twelve previously undescribed venom peptides. Selected peptides were tested for binding to the receptor-binding domain (RBD) of the SARSCoV-2 spike protein and inhibition of the spike RBD - human angiotensin-converting enzyme 2 (hACE2) interaction using surface plasmon resonance-based assays. Seven peptides showed dose-dependent inhibitory effects, albeit with IC50 in the high micromolar range (117-1202 mu M). The most active peptide was synthesized using solid phase peptide synthesis and tested for its antiviral activity against SARS-CoV-2 (Lineage B.1.1.7). On exposure to the synthetic peptide of a human lung cell line infected with replication-competent SARS-CoV-2, we observed an IC50 of 200 nM, which was nearly 600-fold lower than that observed in the RBD - hACE2 binding inhibition assay. Our results show that scorpion venom peptides can inhibit the SARS-CoV-2 replication although unlikely through inhibition of spike RBD - hACE2 interaction as the primary mode of action. Scorpion venom peptides represent excellent scaffolds for design of novel anti-SARS-CoV-2 constrained peptides. Future studies should fully explore their antiviral mode of action as well as the structural dynamics of inhibition of target virushost interactions.
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| 9. |
- Koskinen, Lars-Owe D., Professor, 1955-
(författare)
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Cerebral and peripheral blood flow effects of TRH in the rat : a role of vagal nerves
- 1989
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 10:5, s. 933-938
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Tidskriftsartikel (refereegranskat)abstract
- The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBF(tot) in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscarinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.
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| 10. |
- Koskinen, Lars-Owe D., Professor, 1955-
(författare)
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Naloxone and TRH affect regional blood flows in the anesthetized rabbit.
- 1991
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 12:6, s. 1273-1277
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Tidskriftsartikel (refereegranskat)abstract
- The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied in the rabbit. Naloxone caused a vasodilation in the myocardium and adrenal glands. Naloxone elicited an increment in cerebral blood flow in several regions which attenuated the cerebrovasodilating effect of TRH in a few regions. The blockade of endogenous opioids with naloxone did not modify the peripheral vasoconstricting effect of TRH or affect the vascular effects of TRH mediated by the peripheral sympathetic nerves. The results indicate that naloxone has a vasodilating effect in the myocardium and CNS in anesthetized rabbits. The major part of the cardiovascular effect of TRH is not dependent on mechanisms sensitive to naloxone.
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