Excimer, Ho:YAG, and Q-switched Ho:YAG ablation of aorta: a comparison of temperatures and tissue damage in vitro

1993 ◽  
Vol 32 (4) ◽  
pp. 526 ◽  
Author(s):  
E. Duco Jansen ◽  
Tuong H. Le ◽  
Ashley J. Welch
Keyword(s):  
Tissue Damage

scholarly journals Nanobody-Mediated Inhibition of P2X7 on Microglia Improves Stroke Outcome

2021 ◽  
Author(s):  
Maximilian Wilmes ◽  
Carolina Pinto Espinoza ◽  
Peter Ludewig ◽  
Arthur Liesz ◽  
Annette Nicke ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Transgenic Mice ◽  
Tissue Damage ◽  
Calcium Influx ◽  
Atp Release ◽  
Artery Occlusion ◽  
Membrane Pores ◽  
Caspase 1 ◽  
Ischemic Tissue

Abstract BackgroundPrevious studies have demonstrated that purinergic receptors could be therapeutic targets to modulate the inflammatory response in multiple brain disease models. However, tools for the selective and efficient targeting of these receptors are scarce. The new development of P2X7-specific nanobodies (nbs) enables us to effectively block the P2X7-channel.MethodsTemporary middle cerebral artery occlusion (tMCAO) in wildtype and P2X7-transgenic mice was used as a model for ischemic stroke. ATP release was assessed in transgenic ATP sensor mice. Stroke size was measured without treatment and after injection of P2X7-specific nbs i.v. and i.c.v. directly before tMCAO-surgery. P2X7-GFP expressing transgenic mice were used to show immunhistochemically P2X7 distribution in the brain. In vitro cultured microglia were used to investigate calcium-influx, pore-formation via DAPI uptake, caspase 1 activation and IL-1b release after incubation with P2X7-specific nbs. ResultsATP sensor mice showed an increase of ATP-release in the ischemic hemisphere compared to the contralateral hemisphere or sham mice up to 24 h after stroke. We could further verify the role of the ATP-P2X7 axis in P2X7-overexpressing mice, which showed significantly greater stroke volumes after 24 h. In vitro experiments with primary microglia cells showed that P2X7-specific nanobodies were capable of dampening the ATP-trigged calcium-influx and formation of membrane pores measured by Fluo4 fluorescence or DAPI uptake. We found a lower caspase 1 activity and a subsequently lower IL-1b release. However, the intravenous (i.v.) injection of P2X7-specific nanobodies compared to isotype controls before the tMCAO-surgery did not result in smaller stroke size compared to isotype controls. As demonstrated by FACS, nbs had only reached brain infiltrating macrophages but not microglia. To reach microglia, we injected the P2X7-spezific nbs or the isotype directly intraventricularly (icv). 30 mg of P2X7-specific nbs proved efficient for microglial targeting, reducing post-stroke microglia activation and stroke size significantly.ConclusionHere, we demonstrate the importance of locally produced ATP for the tissue damage observed in ischemic stroke and we show the potential of icv injected P2X7-specific nbs to reduce ischemic tissue damage.

Hymenolepis murissylvatici: humoral response in intestinal lavages of the mouse

1989 ◽  
Vol 63 (1) ◽  
pp. 25-31 ◽  
Author(s):  
E. Van Der Vorst ◽  
H. Dhont ◽  
C. Van Haeren ◽  
R. Deceunynck ◽  
P. H. De Rycke
Keyword(s):  
Tissue Damage ◽  
Humoral Response ◽  
Specific Ige ◽  
Immune Serum ◽  
Apparent Effect ◽  
Igm Antibodies ◽  
Immunological Reactions

ABSTRACTHymenolepis murissylvatici elicits a humoral response in serum and in the intestine of the mouse from which it is immunologically rejected. In serum, significant differences were recorded 3 days after reinfection, while in intestinal lavages it takes place from day 9 after reinfection. In serum the response is largely the result of IgG and IgM antibodies whereas in the intestine, IgA is the most abundant antibody. Although specific IgE could not be demonstrated in serum, it was present in intestinal lavages, although rather late (i.e. day 14 after reinfection). Treatment of young worms in vitro both with immune serum or intestinal lavages had no apparent effect on their viability. Immune serum produced a complement independent precipitation on the surface of the worms in vitro. This reaction did not affect viability or infectivity of the parasite, as demonstrated by the successful implantation of treated worms in recipient mice. The above-mentioned results, together with the knowledge that the Hymenolepis model has no tissue stages and causes no tissue damage, make it probable that further study of this model will reveal some specific intestinal immunological reactions.

scholarly journals The Pathogenic Potential of Proteus mirabilis Is Enhanced by Other Uropathogens during Polymicrobial Urinary Tract Infection

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Chelsie E. Armbruster ◽  
Sara N. Smith ◽  
Alexandra O. Johnson ◽  
Valerie DeOrnellas ◽  
Kathryn A. Eaton ◽  
...  
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Disease Severity ◽  
Proteus Mirabilis ◽  
Tissue Damage ◽  
Urease Activity ◽  
Pathogenic Potential ◽  
Content Type

ABSTRACT Urinary catheter use is prevalent in health care settings, and polymicrobial colonization by urease-positive organisms, such as Proteus mirabilis and Providencia stuartii, commonly occurs with long-term catheterization. We previously demonstrated that coinfection with P. mirabilis and P. stuartii increased overall urease activity in vitro and disease severity in a model of urinary tract infection (UTI). In this study, we expanded these findings to a murine model of catheter-associated UTI (CAUTI), delineated the contribution of enhanced urease activity to coinfection pathogenesis, and screened for enhanced urease activity with other common CAUTI pathogens. In the UTI model, mice coinfected with the two species exhibited higher urine pH values, urolithiasis, bacteremia, and more pronounced tissue damage and inflammation compared to the findings for mice infected with a single species, despite having a similar bacterial burden within the urinary tract. The presence of P. stuartii, regardless of urease production by this organism, was sufficient to enhance P. mirabilis urease activity and increase disease severity, and enhanced urease activity was the predominant factor driving tissue damage and the dissemination of both organisms to the bloodstream during coinfection. These findings were largely recapitulated in the CAUTI model. Other uropathogens also enhanced P. mirabilis urease activity in vitro, including recent clinical isolates of Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. We therefore conclude that the underlying mechanism of enhanced urease activity may represent a widespread target for limiting the detrimental consequences of polymicrobial catheter colonization, particularly by P. mirabilis and other urease-positive bacteria.

Growth factor and cytokine expression of human mesenchymal stromal cells is not altered in an in vitro model of tissue damage

Cytotherapy ◽  
2010 ◽  
Vol 12 (7) ◽  
pp. 870-880 ◽  
Author(s):  
Katrin Montzka ◽  
Tobias Führmann ◽  
Jochen Müller-Ehmsen ◽  
Michael Wöltje ◽  
Gary A. Brook
Keyword(s):  
Growth Factor ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Tissue Damage ◽  
In Vitro Model ◽  
Cytokine Expression ◽  
Human Mesenchymal Stromal Cells ◽  
Vitro Model

scholarly journals An Anterior Cruciate Ligament Failure Mechanism

2019 ◽  
Vol 47 (9) ◽  
pp. 2067-2076 ◽  
Author(s):  
Junjie Chen ◽  
Jinhee Kim ◽  
Wenhao Shao ◽  
Stephen H. Schlecht ◽  
So Young Baek ◽  
...  
Keyword(s):  
Anterior Cruciate Ligament ◽  
Body Weight ◽  
Infrared Spectroscopy ◽  
Tissue Damage ◽  
Second Harmonic ◽  
Cruciate Ligament ◽  
Acl Injuries ◽  
Acl Failure ◽  
Anterior Cruciate

Background: Nearly three-quarters of anterior cruciate ligament (ACL) injuries occur as “noncontact” failures from routine athletic maneuvers. Recent in vitro studies revealed that repetitive strenuous submaximal knee loading known to especially strain the ACL can lead to its fatigue failure, often at the ACL femoral enthesis. Hypothesis: ACL failure can be caused by accumulated tissue fatigue damage: specifically, chemical and structural evidence of this fatigue process will be found at the femoral enthesis of ACLs from tested cadaveric knees, as well as in ACL explants removed from patients undergoing ACL reconstruction. Study Design: Controlled laboratory study. Methods: One knee from each of 7 pairs of adult cadaveric knees were repetitively loaded under 4 times–body weight simulated pivot landings known to strain the ACL submaximally while the contralateral, unloaded knee was used as a comparison. The chemical and structural changes associated with this repetitive loading were characterized at the ACL femoral enthesis at multiple hierarchical collagen levels by employing atomic force microscopy (AFM), AFM–infrared spectroscopy, molecular targeting with a fluorescently labeled collagen hybridizing peptide, and second harmonic imaging microscopy. Explants from ACL femoral entheses from the injured knee of 5 patients with noncontact ACL failure were also characterized via similar methods. Results: AFM–infrared spectroscopy and collagen hybridizing peptide binding indicate that the characteristic molecular damage was an unraveling of the collagen molecular triple helix. AFM detected disruption of collagen fibrils in the forms of reduced topographical surface thickness and the induction of ~30- to 100-nm voids in the collagen fibril matrix for mechanically tested samples. Second harmonic imaging microscopy detected the induction of ~10- to 100-µm regions where the noncentrosymmetric structure of collagen had been disrupted. These mechanically induced changes, ranging from molecular to microscale disruption of normal collagen structure, represent a previously unreported aspect of tissue fatigue damage in noncontact ACL failure. Confirmatory evidence came from the explants of 5 patients undergoing ACL reconstruction, which exhibited the same pattern of molecular, nanoscale, and microscale structural damage detected in the mechanically tested cadaveric samples. Conclusion: The authors found evidence of accumulated damage to collagen fibrils and fibers at the ACL femoral enthesis at the time of surgery for noncontact ACL failure. This tissue damage was similar to that found in donor knees subjected in vitro to repetitive 4 times–body weight impulsive 3-dimensional loading known to cause a fatigue failure of the ACL. Clinical Relevance: These findings suggest that some ACL injuries may be due to an exacerbation of preexisting hierarchical tissue damage from activities known to place larger-than-normal loads on the ACL. Too rapid an increase in these activities could cause ACL tissue damage to accumulate across length scales, thereby affecting ACL structural integrity before it has time to repair. Prevention necessitates an understanding of how ACL loading magnitude and frequency are anabolic, neutral, or catabolic to the ligament.

scholarly journals Neutrophil azurophilic granule exocytosis is primed by TNF-α and partially regulated by NADPH oxidase

2016 ◽  
Vol 22 (8) ◽  
pp. 635-646 ◽  
Author(s):  
Renee M Potera ◽  
Melissa J Jensen ◽  
Brieanna M Hilkin ◽  
Gina K South ◽  
Jessica S Hook ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Tissue Damage ◽  
Chronic Inflammatory Disease ◽  
Host Tissue ◽  
Ros Generation ◽  
Oxygen Species ◽  
Granule Exocytosis ◽  
Azurophilic Granule ◽  
Tnf Α

Neutrophil (polymorphonuclear leukocyte) activation with release of granule contents plays an important role in the pathogenesis of acute lung injury, prompting clinical trials of inhibitors of neutrophil elastase. Despite mounting evidence for neutrophil-mediated host tissue damage in a variety of disease processes, mechanisms regulating azurophilic granule exocytosis at the plasma membrane, and thus release of elastase and other proteases, are poorly characterized. We hypothesized that azurophilic granule exocytosis would be enhanced under priming conditions similar to those seen during acute inflammatory events and during chronic inflammatory disease, and selected the cytokine TNF-α to model this in vitro. Neutrophils stimulated with TNF-α alone elicited intracellular reactive oxygen species (ROS) generation and mobilization of secretory vesicles, specific, and gelatinase granules. p38 and ERK1/2 MAPK were involved in these components of priming. TNF-α priming alone did not mobilize azurophilic granules to the cell surface, but did markedly increase elastase release into the extracellular space in response to secondary stimulation with N-formyl-Met-Leu-Phe (fMLF). Priming of fMLF-stimulated elastase release was further augmented in the absence of NADPH oxidase-derived ROS. Our findings provide a mechanism for host tissue damage during neutrophil-mediated inflammation and suggest a novel anti-inflammatory role for the NADPH oxidase.

The relationship between milk yield, composition and tissue damage in a case of subclinical mastitis

1963 ◽  
Vol 30 (1) ◽  
pp. 23-33 ◽  
Author(s):  
R. Waite ◽  
P. S. Blackburn
Keyword(s):  
Chemical Composition ◽  
Milk Yield ◽  
Tissue Damage ◽  
Subclinical Mastitis ◽  
Bacteriological Examination ◽  
Cell Content ◽  
Upper Level ◽  
The Relationship ◽  
Number Of Cells

SummaryA chemical, cytological and bacteriological examination of the milk from each quarter of a cow suffering from subclinical mastitis, but giving 5–6 gal of milk per day, was made at weekly intervals during the first 84 days after parturition. The infection, caused by micrococcal and staphylococcal bacteria, resisted repeated treatments with various antibiotics administered via the teat canals and also intramuscularly, although in vitro the bacteria were susceptible to all the antibiotics used. The cow was slaughtered and a histological examination made of the udder in an attempt to establish the cause of the continuing infection and to assess the extent of tissue damage. Two quarters each contained large abscesses in the upper level of the udder and these could have acted as reservoirs of infection; no cause was established for the other two quarters and it can only be assumed that reinfection occurred from the two abscessed quarters.The amount of active lesions in the lobules of all the quarters was small, 1–6%, but half or more of all the lobules were involuted, although only a minority appeared to have involuted as a result of infection. In the two abscessed quarters there was extensive damage to the duct system, 23 and 31% showing lesions.When the milk contained an abnormally large number of cells the chemical composition was also abnormal, containing less lactose (and hence less solids-not-fat) and having a nitrogen distribution in which there was more blood serum albumin and globulin and less casein than usual. Cell content and chemical composition were better indicators of tissue damage than the presence of mastitis organisms. It is estimated that the solids-not-fat content of the milk of the whole udder as a result of the infections was considerably lower than it would otherwise have been (8·0 instead of 8·8%) and that the daily loss in milk yield was about 9 lb.

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