Effect ofSchistosoma mansoni-induced granulomatous inflammation on murine gastrointestinal motility

2001 ◽  
Vol 280 (5) ◽  
pp. G1030-G1042 ◽  
Author(s):  
Tom G. Moreels ◽  
Joris G. De Man ◽  
Johannes J. Bogers ◽  
Benedicte Y. De Winter ◽  
Gunther Vrolix ◽  
...  
Keyword(s):  
Structural Changes ◽  
Gastrointestinal Transit ◽  
Granulomatous Inflammation ◽  
Muscle Layer ◽  
Gastric Fundus ◽  
Smooth Muscle Contractility ◽  
Functional Changes ◽  
Mucosal Thickness

In Schistosoma mansoni-infected mice, gastrointestinal transit was measured in vivo and the neuromuscular function of longitudinal muscle strips of inflamed ileum and noninflamed gastric fundus was assessed in vitro. Eight weeks after infection, the ileal wall was acutely inflamed, as shown by a mucosal inflammatory infiltrate, leading to an increase in mucosal thickness, in myeloperoxidase (MPO) activity, and in interleukin (IL)-1β production. At that time, both gastrointestinal transit and in vitro ileal contractility were normal. Twelve weeks after infection, chronic granulomatous inflammation led to proliferation of the muscle layer and to a further increase in MPO activity, whereas IL-1β production normalized. Gastrointestinal transit was decreased, whereas in vitro ileal contractility was increased irrespective of the contractile stimulus. In vitro incubation with IL-1β (10 ng/ml for 60 min) significantly increased ileal contractility only at 8 wk after infection. Indomethacin, tetrodotoxin, and atropine had no differential effect on ileal contractility in controls and infected mice. In vitro contractility of noninflamed gastric fundus was normal both 8 and 12 wk after infection. We conclude that intestinal schistosomiasis 8 wk after infection is associated only with structural changes of the ileum, whereas 12 wk after infection, both structural and functional changes are present. These changes are characterized by increased ileal wall thickness, decreased gastrointestinal transit, and increased smooth muscle contractility restricted to the inflamed gut segment.

Potential Antiulcer Agents From Plants: A Comprehensive Review

2019 ◽  
Vol 5 (3) ◽  
pp. 170-231
Author(s):  
Minky Mukhija ◽  
Bhuwan Chandra Joshi
Keyword(s):  
Medicinal Plants ◽  
Developed Countries ◽  
Scientific Data ◽  
Antiulcer Activity ◽  
Peptic Ulcers ◽  
Comprehensive Review ◽  
Chemical Structures ◽  
Mucosal Thickness

Background: Peptic ulcer is a deep gastrointestinal erosion disorder that involves the entire mucosal thickness and can even penetrate the muscular mucosa. Nowadays, several plants and compounds derived from it have been screened for their antiulcer activity. In the last few years, there has been an exponential growth in the field of herbal medicine. This field has gained popularity in both developing and developed countries because of their natural origin and less side effects. Objective: This review aims to provide a comprehensive summary of currently available knowledge of medicinal plants and phytoconstituents reported for their anti-ulcer properties. Methods: The worldwide accepted database like SCOPUS, PUBMED, SCIELO, NISCAIR, ScienceDirect, Springerlink, Web of Science, Wiley, SciFinder and Google Scholar were used to retrieve available published literature. Results: A comprehensive review of the present paper is an attempt to list the plants with antiulcer activity. The review narrates the dire need to explore potential chemical moieties that exert an antiulcer effect, from unexploited traditional plants. Furthermore, the present study reveals the intense requirement to exploit the exact mechanism through which either the plant extracts or their active constituents exhibit their antiulcer properties. Conclusion: This article is the compilation of the plants and its constituents reported for the treatment of peptic ulcers. The Comprehensive data will surely attract the number of investigators to initiate further research that might lead to the drugs for the treatment of ulcers. As sufficient scientific data is not available on plants, most of the herbals cannot be recommended for the treatment of diseases. This can be achieved by research on pure chemical structures derived from plants or to prepare new lead compounds with proven beneficial preclinical in vitro and in vivo effects. However, a lot remains to be done in further investigations for the better status of medicinal plants.

scholarly journals Interaction of Lactoferrin with Unsaturated Fatty Acids: In Vitro and In Vivo Study of Human Lactoferrin/Oleic Acid Complex Cytotoxicity

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1602
Author(s):  
Anna Elizarova ◽  
Alexey Sokolov ◽  
Valeria Kostevich ◽  
Ekaterina Kisseleva ◽  
Evgeny Zelenskiy ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Structural Changes ◽  
Unsaturated Fatty Acids ◽  
Structural Features ◽  
Control Group ◽  
Acid Complex ◽  
Hepatoma 22A ◽  
Constitutive Parameters

As shown recently, oleic acid (OA) in complex with lactoferrin (LF) causes the death of cancer cells, but no mechanism(s) of that toxicity have been disclosed. In this study, constitutive parameters of the antitumor effect of LF/OA complex were explored. Complex LF/OA was prepared by titrating recombinant human LF with OA. Spectral analysis was used to assess possible structural changes of LF within its complex with OA. Structural features of apo-LF did not change within the complex LF:OA = 1:8, which was toxic for hepatoma 22a cells. Cytotoxicity of the complex LF:OA = 1:8 was tested in cultured hepatoma 22a cells and in fresh erythrocytes. Its anticancer activity was tested in mice carrying hepatoma 22a. In mice injected daily with LF-8OA, the same tumor grew significantly slower. In 20% of animals, the tumors completely resolved. LF alone was less efficient, i.e., the tumor growth index was 0.14 for LF-8OA and 0.63 for LF as compared with 1.0 in the control animals. The results of testing from 48 days after the tumor inoculation showed that the survival rate among LF-8OA-treated animals was 70%, contrary to 0% rate in the control group and among the LF-treated mice. Our data allow us to regard the complex of LF and OA as a promising tool for cancer treatment.

scholarly journals Brown Spiders’ Phospholipases-D with Potential Therapeutic Applications: Functional Assessment of Mutant Isoforms

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 320
Author(s):  
Thaís Pereira da Silva ◽  
Fernando Jacomini de Castro ◽  
Larissa Vuitika ◽  
Nayanne Louise Costacurta Polli ◽  
Bruno César Antunes ◽  
...  
Keyword(s):  
Structural Changes ◽  
Capillary Permeability ◽  
Structural Data ◽  
Histopathological Analysis ◽  
Amino Acid Residues ◽  
Wild Type ◽  
Antigenic Properties ◽  
Harmful Effects

Phospholipases-D (PLDs) found in Loxosceles spiders’ venoms are responsible for the dermonecrosis triggered by envenomation. PLDs can also induce other local and systemic effects, such as massive inflammatory response, edema, and hemolysis. Recombinant PLDs reproduce all of the deleterious effects induced by Loxosceles whole venoms. Herein, wild type and mutant PLDs of two species involved in accidents—L. gaucho and L. laeta—were recombinantly expressed and characterized. The mutations are related to amino acid residues relevant for catalysis (H12-H47), magnesium ion coordination (E32-D34) and binding to phospholipid substrates (Y228 and Y228-Y229-W230). Circular dichroism and structural data demonstrated that the mutant isoforms did not undergo significant structural changes. Immunoassays showed that mutant PLDs exhibit conserved epitopes and kept their antigenic properties despite the mutations. Both in vitro (sphingomyelinase activity and hemolysis) and in vivo (capillary permeability, dermonecrotic activity, and histopathological analysis) assays showed that the PLDs with mutations H12-H47, E32-D34, and Y228-Y229-W230 displayed only residual activities. Results indicate that these mutant toxins are suitable for use as antigens to obtain neutralizing antisera with enhanced properties since they will be based on the most deleterious toxins in the venom and without causing severe harmful effects to the animals in which these sera are produced.

scholarly journals Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a

2016 ◽  
Vol 311 (5) ◽  
pp. G964-G973 ◽  
Author(s):  
Jagmohan Singh ◽  
Ettickan Boopathi ◽  
Sankar Addya ◽  
Benjamin Phillips ◽  
Isidore Rigoutsos ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Anal Sphincter ◽  
Internal Anal Sphincter ◽  
Smooth Muscles ◽  
Smooth Muscle Contractility ◽  
Network Analyses ◽  
Rhoa Signaling

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets ( Eln, Col3a1, Col1a1, Zeb2, Myocd, Srf, Smad1, Smad2, Rhoa/Rock2, Fn1, Tagln v2, Klf4, and Acta2) involved in regulation of smooth muscle contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF, and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist [U-46619 (thromboxane A2analog)]-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Last, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone and suggests that miR-133a is a feasible therapeutic target in aging-associated rectoanal incontinence.

Espace extracellulaire, perméabilité à l'inuline et accumulation de L-alanine dans l'intestin isolé de Grenouille

1973 ◽  
Vol 51 (1) ◽  
pp. 22-28
Author(s):  
Joël de la Noüe ◽  
André Gagnon
Keyword(s):  
Extracellular Space ◽  
Muscle Layer ◽  
Solute Concentration ◽  
Tissue Water ◽  
Intracellular Amino Acid ◽  
Inulin Space ◽  
Total Tissue ◽  
Frog Intestine

In order to calculate the intracellular concentration of accumulated L-alanine, the extracellular space (inulin-14C) of frog intestine was measured. To check the validity of the technique, frog liver and gastrocnemius were used too. By scraping proximal portions of intestine, the inulin space was found to be similar (around 20% of total tissue water) in both the muscle layer and the mucosa. The mucosal epithelium is an imperfect barrier to inulin while the serosa is very permeable. These results suggest that the interstitial solute concentration is best approximated by equating it to that of the serosal solution. The in vitro inulin space, compared to the in vivo one, increases with time, as does the cellular hydration. The data obtained from measurements of extracellular space and from L-alanine uptake show that the intracellular amino acid is in a free state.

scholarly journals Putative Autocleavage of Outer Capsid Protein μ1, Allowing Release of Myristoylated Peptide μ1N during Particle Uncoating, Is Critical for Cell Entry by Reovirus

2004 ◽  
Vol 78 (16) ◽  
pp. 8732-8745 ◽  
Author(s):  
Amy L. Odegard ◽  
Kartik Chandran ◽  
Xing Zhang ◽  
John S. L. Parker ◽  
Timothy S. Baker ◽  
...  
Keyword(s):  
Capsid Protein ◽  
Structural Changes ◽  
General Mechanism ◽  
Membrane Penetration ◽  
Outer Capsid Protein ◽  
Core Proteins ◽  
Peptide Release ◽  
Outer Capsid

ABSTRACT Several nonenveloped animal viruses possess an autolytic capsid protein that is cleaved as a maturation step during assembly to yield infectious virions. The 76-kDa major outer capsid protein μ1 of mammalian orthoreoviruses (reoviruses) is also thought to be autocatalytically cleaved, yielding the virion-associated fragments μ1N (4 kDa; myristoylated) and μ1C (72 kDa). In this study, we found that μ1 cleavage to yield μ1N and μ1C was not required for outer capsid assembly but contributed greatly to the infectivity of the assembled particles. Recoated particles containing mutant, cleavage-defective μ1 (asparagine → alanine substitution at amino acid 42) were competent for attachment; processing by exogenous proteases; structural changes in the outer capsid, including μ1 conformational change and σ1 release; and transcriptase activation but failed to mediate membrane permeabilization either in vitro (no hemolysis) or in vivo (no coentry of the ribonucleotoxin α-sarcin). In addition, after these particles were allowed to enter cells, the δ region of μ1 continued to colocalize with viral core proteins in punctate structures, indicating that both elements remained bound together in particles and/or trapped within the same subcellular compartments, consistent with a defect in membrane penetration. If membrane penetration activity was supplied in trans by a coinfecting genome-deficient particle, the recoated particles with cleavage-defective μ1 displayed much higher levels of infectivity. These findings led us to propose a new uncoating intermediate, at which particles are trapped in the absence of μ1N/μ1C cleavage. We additionally showed that this cleavage allowed the myristoylated, N-terminal μ1N fragment to be released from reovirus particles during entry-related uncoating, analogous to the myristoylated, N-terminal VP4 fragment of picornavirus capsid proteins. The results thus suggest that hydrophobic peptide release following capsid protein autocleavage is part of a general mechanism of membrane penetration shared by several diverse nonenveloped animal viruses.

Abstract 585: Endothelial Cells from Adipose Tissue of Obese Humans Display Mesenchymal Characteristics

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Bronson A Haynes ◽  
Eric J Lehrer ◽  
Giann J Bhatt ◽  
Ryan W Huyck ◽  
Ashley N James ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Adipose Tissue ◽  
Prolonged Exposure ◽  
Endothelial Permeability ◽  
Fold Increase ◽  
Atp Production ◽  
Functional Changes ◽  
Twist 1

The mechanisms underlying vascular dysfunction in adipose tissue (AT) in obesity are not clearly understood. Our hypothesis is that in response to pro-inflammatory cytokines (PIC) present in obese AT, endothelial cells (EC) can de-differentiate and acquire a mesenchymal-like phenotype (EndoMT) that leads to endothelial dysfunction. To test our hypothesis, we measured endothelial and mesenchymal markers of CD31 + CD34 + EC isolated from omental (OM) and subcutaneous (SC) AT of bariatric subjects (BAMVEC) using RT-PCR and western blot. Permeability and oxidative metabolism were determined by ECIS and Seahorse analyzer XF e 24, respectively. BAMVEC isolated from both OM and SC fat showed very low protein expression of vWF and VE-Cadherin (EC markers) and abundantly expressed αSMA and the EMT transcription factor twist-1. To determine effects of PIC on EndoMT, commercially available primary endothelial cells from AT (HAMVEC) were treated in vitro with PIC (2.5ng/mL TNFα, IFNγ and TGFβ) for 1, 3 or 6 days. We found progressive down-regulation by >2-fold (p<0.001) of the EC markers vWF, VE-Cadherin, and Occludin compared to controls. As early as 1 day of PIC treatment twist-1 (p<0.001) and snail1 (p<0.05) showed an increase by >2-fold. Similarly, OM and SC BAMVEC expressed >2-fold increase in the mesenchymal genes twist-1, FSP1, αSMA, and snail1 compared to untreated HAMVEC. Metabolically, BAMVEC had increased ATP production and maximal respiration compared to HAMVEC suggesting increased oxidative phosphorylation, a marker of mesenchymal-like cells. PIC stimulation of HAMVEC yielded significant increases in endothelial permeability and motility (p<0.001). Notably, there were no significant differences in any of the markers between OM and SC BAMVEC. These results show that EC in obese AT exhibit a mesenchymal-like phenotype which may account for functional changes such as increased permeability and migration and are not depot specific. Using primary EC from human AT we showed that prolonged exposure to PIC induces a phenotype similar to CD31+CD34+ EC from obese AT. This supports the concept that AT inflammation can promote EC de-differentiation in vivo and our in vitro model is suitable for future studies to uncover the relevant mechanisms.

scholarly journals Increased in vitro and in vivo generation of procoagulant activity (tissue factor) by mononuclear phagocytes after intralipid infusion in rabbits

Blood ◽  
1985 ◽  
Vol 65 (6) ◽  
pp. 1391-1395 ◽  
Author(s):  
P Montemurro ◽  
A Lattanzio ◽  
G Chetta ◽  
L Lupo ◽  
L Caputi-Iambrenghi ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Mononuclear Cells ◽  
Mononuclear Phagocyte ◽  
Mononuclear Phagocytes ◽  
Procoagulant Activity ◽  
Sterile Saline ◽  
Functional Changes ◽  
Before And After

Abstract Intralipid, a fat emulsion widely used in parenteral nutrition, can produce marked functional changes of the mononuclear phagocyte system. We investigated the effect of Intralipid administration on the generation of procoagulant activity by rabbit mononuclear phagocytes. Two groups of ten rabbits given either a single infusion of Intralipid 10% or a similar volume of sterile saline were studied before and after infusion. Procoagulant activity was measured on isolated blood mononuclear cells after incubation with and without endotoxin, using a one-stage clotting assay. Cells from animals infused with Intralipid produced significantly more procoagulant activity than controls (P less than .01). Results were similar when freshly collected whole blood was incubated with and without endotoxin, and procoagulant activity was measured on subsequently isolated mononuclear cells (P less than .01). In addition, when rabbits were given a single injection of endotoxin, blood and spleen mononuclear cells harvested 50 to 60 minutes after the injection from animals pretreated with Intralipid expressed five to seven times more procoagulant activity than did cells from animals pretreated with saline. In all instances, procoagulant activity was identified as tissue factor. These findings suggest that Intralipid may cause functional changes in mononuclear phagocytes, resulting in increased production of tissue factor on incubation in short-term culture in vitro and in response to endotoxin in vivo.

scholarly journals Functional Changes Of Fetal Muscle Acetylcholine Receptor During Mouse Development

Physiology ◽  
1998 ◽  
Vol 13 (5) ◽  
pp. 247-251
Author(s):  
Francesca Grassi ◽  
Fabrizio Eusebi
Keyword(s):  
Acetylcholine Receptor ◽  
Single Channel ◽  
Splice Variants ◽  
Mouse Development ◽  
Functional Changes ◽  
Γ Subunit ◽  
Muscle Innervation ◽  
Fetal Muscle

In developing muscles in vivo and in vitro, the acetylcholine receptor γ-subunit exists in two splice variants, conferring different single-channel open durations (τop) to reconstituted receptors. In mouse muscles, τop changes around birth, possibly as receptors incorporate either variant of γ-subunit. This might be relevant to the concomitant maturation of muscle innervation.

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