A Short Review of Experimental Peritoneal Sclerosis: From Mice to Men

2005 ◽  
Vol 28 (2) ◽  
pp. 97-104 ◽  
Author(s):  
L. Gotloib ◽  
V. Wajsbrot ◽  
A. Shostak

Peritoneal sclerosis has been induced in rodents in vivo by exposing the membrane to a variety of experimental interventions: asbestos, 0.1% chlorexidine, iron dextran, glucose degradation products, AGE deposits derived from uremia per se, sodium hypochlorite, lypopolysaccharide, low pH, pure water, silica or zymosan. With a few exceptions (pure water, chlorhexidine and low pH), the other substances mentioned operate setting out different degrees of oxidative stress. This short review describes several experimental interventions in rodents, aimed at acute exfoliation or long-term, sustained injury of the mesothelial monolayer performed by means of intraperitoneal injections of different oxidant agents. Acute exfoliation induced by deoxycholate resulted in a depopulated monolayer coincident with immediate alteration of the peritoneal permeability, evidenced by increased urea D/P ratio, higher glucose absorption rate, elevated albumin losses in the effluent and significant reduction of the ultrafiltration rate. In the long term (30 days), these manifestations of membrane failure persisted and coincided with substantial peritoneal sclerosis. Peritoneal sclerosis was also induced by IP injections of 0.125% trypsin and 6.6 mM/L solution of formaldehyde. Using the doughnut rat model of mesothelial regeneration, exposure to 4.25% glucose or 7.5% icodextrin solutions severely hampered repopulation of the monolayer, which was replaced by a thick sheet of fibrous tissue. It is concluded that peritoneal sclerosis derives mostly from sustained oxidative injury to the peritoneal membrane. Loss of the mesothelial monolayer is the first step in the chain of events leading to this complication.

Author(s):  
Lindsey R. VanSchoiack ◽  
Veronica I. Shubayev ◽  
Robert R. Myers ◽  
James C. Earthman

The process of osseointegration is the firm anchoring of a surgical implant by the growth of bone around it without fibrous tissue formation at the interface. This process is critical for long-term implant success. The ability to monitor this process in vivo would allow for personalization of loading protocols to increase the rate of implant success overall by ensuring that implants are not over or under loaded during recovery. Accordingly, there is a strong need for an instrument that has the sensitivity to noninvasively measure osseointegration in vivo. One of the objectives of the present study was to assess the performance of an instrumented percussion probe for quantitatively monitoring the osseointegration process.


2013 ◽  
Vol 750-752 ◽  
pp. 1651-1655
Author(s):  
Bai Yan Sui ◽  
Cheng Tie Wu ◽  
Jiao Sun

Mesoporous bioactive glass (MBG) has superior bioactivity and degradation than non-mesoporous bioactive glass (BG) in vitro. But the biological effect of MBG in vivo is still unknown. In this study, MBG powders with 20μm were implanted into the femoral condyles in SD rats. BG powders with 20μm were used as a control. The local degradation and osteogenesis were observed at 1 week and 4 weeks after implantation, and the systemic toxicity of the degradation products were also evaluated simultaneously. The results revealed MBG powders had the faster rate of degradation and better osteogenesis effect than BG powders at 4 weeks, although the most of material still remained in situ. Histopathological analyses indicated the degradation products did not have any damage to major organs such as liver and kidney. In conclusion, this preliminary study demonstrated that MBG powders have more excellent biological effect at 4 weeks than that of BG in vivo. However the long-term effect needs to be confirmed.


2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Simone Maschauer ◽  
Olaf Prante

At the time when the highly efficient [18F]FDG synthesis was discovered by the use of the effective precursor 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulfonyl-β-D-mannopyranose (mannose triflate) for nucleophilic18F-substitution, the field of PET in nuclear medicine experienced a long-term boom. Thirty years later, various strategies for chemoselective18F-labeling of biomolecules have been developed, trying to keep up with the emerging field of radiopharmaceutical sciences. Among the new radiochemical strategies, chemoselective18F-fluoroglycosylation methods aim at the sweetening of pharmaceutical radiochemistry by providing a powerful and highly valuable tool for the design of18F-glycoconjugates with suitablein vivoproperties for PET imaging studies. This paper provides a short review (reflecting the literature not older than 8 years) on the different18F-fluoroglycosylation reactions that have been applied to the development of various18F-glycoconjugate tracers, including not only peptides, but also nonpeptidic tracers and high-molecular-weight proteins.


Author(s):  
Hajnal Klelemen ◽  
Gabriel Hancu ◽  
Edina Kacsó ◽  
Lajos-Attila Papp

Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed.


2019 ◽  
Vol 117 (1) ◽  
pp. 103-113 ◽  
Author(s):  
Alice Balfourier ◽  
Nathalie Luciani ◽  
Guillaume Wang ◽  
Gerald Lelong ◽  
Ovidiu Ersen ◽  
...  

Gold nanoparticles are used in an expanding spectrum of biomedical applications. However, little is known about their long-term fate in the organism as it is generally admitted that the inertness of gold nanoparticles prevents their biodegradation. In this work, the biotransformations of gold nanoparticles captured by primary fibroblasts were monitored during up to 6 mo. The combination of electron microscopy imaging and transcriptomics study reveals an unexpected 2-step process of biotransformation. First, there is the degradation of gold nanoparticles, with faster disappearance of the smallest size. This degradation is mediated by NADPH oxidase that produces highly oxidizing reactive oxygen species in the lysosome combined with a cell-protective expression of the nuclear factor, erythroid 2. Second, a gold recrystallization process generates biomineralized nanostructures consisting of 2.5-nm crystalline particles self-assembled into nanoleaves. Metallothioneins are strongly suspected to participate in buildings blocks biomineralization that self-assembles in a process that could be affected by a chelating agent. These degradation products are similar to aurosomes structures revealed 50 y ago in vivo after gold salt therapy. Overall, we bring to light steps in the lifecycle of gold nanoparticles in which cellular pathways are partially shared with ionic gold, revealing a common gold metabolism.


2014 ◽  
Vol 62 (S 01) ◽  
Author(s):  
M. Sigler ◽  
S. Huell ◽  
R. Foth ◽  
W. Ruschewski ◽  
T. Tirilomis ◽  
...  

1974 ◽  
Vol 32 (02/03) ◽  
pp. 417-431 ◽  
Author(s):  
A. du P Heyns ◽  
D. J van den Berg ◽  
G. M Potgieter ◽  
F. P Retief

SummaryThe platelet aggregating activity of extracts of different layers of the arterial wall was compared to that of Achilles tendon. Arterial media and tendon extracts, adjusted to equivalent protein content as an index of concentration, aggregated platelets to the same extent but an arterial intima extract did not aggregate platelets. Platelet aggregation induced by collagen could be inhibited by mixing with intima extract, but only to a maximum of about 80%. Pre-mixing adenosine diphosphate (ADP) with intima extracts diminished the platelet aggregation activity of the ADP. Depending on the relationship between ADP and intima extract concentrations aggregating activity could either be completely inhibited or inhibition abolished. Incubation of ADP with intima extract and subsequent separation of degradation products by paper chromatography, demonstrated a time-dependent breakdown of ADP with AMP, adenosine, inosine and hypoxanthine as metabolic products; ADP removal was complete. Collagen, thrombin and adrenaline aggregate platelets mainly by endogenous ADP of the release reaction. Results of experiments comparing inhibition of aggregation caused by premixing aggregating agent with intima extract, before exposure to platelets, and the sequential addition of first the intima extract and then aggregating agent to platelets, suggest that the inhibitory effect of intima extract results from ADP breakdown. It is suggested that this ADP degradation by intima extract may play a protective role in vivo by limiting the size of platelet aggregates forming at the site of minimal “wear and tear” vascular trauma.


1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.


1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken

SummaryCarbon particles cause platelet aggregation in vitro and in vivo. Prior studies established that substances which modify thrombocyte aggregation also influence the rate at which carbon is cleared from the blood.This study was performed in order to elucidate the mechanism by which the carbon-platelet aggregates specifically accumulate in the RES.Activation of fibrinolysis by urokinase or streptokinase reduced the carbon clearance rate, probably due to generated fibrinogen degradation products (FDP). Isolated FDP decreased the carbon clearance and caused disaggregation of platelets and particles in vitro. Inhibition of fibrinolysis by epsilon-amino-caproic acid (EACA), initially accelerated the disappearance of carbon and caused particle accumulation outside the RES, predominantly in the lungs. It is supposed that platelet aggregation and locally activated fibrinolysis act together in the clearance of particles. In the normal situation the RES with its well known low fibrinolytic activity, becomes the receptor of the particles.


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