scholarly journals In-vivo efficacy of biodegradable ultrahigh ductility Mg-Li-Zn alloy tracheal stents for pediatric airway obstruction

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jingyao Wu ◽  
Leila J. Mady ◽  
Abhijit Roy ◽  
Ali Mübin Aral ◽  
Boeun Lee ◽  
...  
Keyword(s):  
Degradation Products ◽  
Metallic Matrix ◽  
Management Technique ◽  
Pediatric Airway ◽  
Endoscopic Techniques ◽  
Airway Stent ◽  
Airway Injury ◽  
Life Threatening

AbstractPediatric laryngotracheal stenosis is a complex congenital or acquired airway injury that may manifest into a potentially life-threatening airway emergency condition. Depending on the severity of obstruction, treatment often requires a combination of endoscopic techniques, open surgical repair, intraluminal stenting, or tracheostomy. A balloon expandable biodegradable airway stent maintaining patency while safely degrading over time may address the complications and morbidity issues of existing treatments providing a less invasive and more effective management technique. Previous studies have focused on implementation of degradable polymeric scaffolds associated with potentially life-threatening pitfalls. The feasibility of an ultra-high ductility magnesium-alloy based biodegradable airway stents was demonstrated for the first time. The stents were highly corrosion resistant under in vitro flow environments, while safely degrading in vivo without affecting growth of the rabbit airway. The metallic matrix and degradation products were well tolerated by the airway tissue without exhibiting any noticeable local or systemic toxicity.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

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.

Accumulation of Macromolecular Particles in the Reticuloendothelial System (RES) Mediated by Platelet Aggregation and Disaggregation

1969 ◽  
Vol 22 (03) ◽  
pp. 496-507 ◽  
Author(s):  
W.G van Aken ◽  
J Vreeken
Keyword(s):  
Platelet Aggregation ◽  
Degradation Products ◽  
Reticuloendothelial System ◽  
Caproic Acid ◽  
Carbon Particles ◽  
Carbon Clearance ◽  
Aggregation And Disaggregation ◽  
Platelet Aggregates

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.

The Effects of Brinolase (Fibrinolytic Enzyme from Aspergillus Oryzae) on Platelet Aggregation of Dog and Man

1972 ◽  
Vol 28 (01) ◽  
pp. 031-048 ◽  
Author(s):  
W. H. E Roschlau ◽  
R Gage
Keyword(s):  
Platelet Aggregation ◽  
Aspergillus Oryzae ◽  
Degradation Products ◽  
Blood Platelet ◽  
Human Platelets ◽  
Fibrinolytic Enzyme ◽  
Inhibitory Effects ◽  
Blood Platelet Aggregation

SummaryInhibition of blood platelet aggregation by brinolase (fibrinolytic enzyme from Aspergillus oryzae) has been demonstrated with human platelets in vitro and with dog platelets in vivo and in vitro, using both ADP and collagen as aggregating stimuli. It is suggested that the optimal inhibitory effects of brinolase occur indirectly through the generation of plasma fibrinogen degradation products, without compromising platelet viability, rather than by direct proteolysis of platelet structures.

scholarly journals Solubility and ADMET profiles of short oligomers of lactic acid

ADMET & DMPK ◽  
2020 ◽  
Author(s):  
Daniela Dascălu ◽  
Diana Larisa Roman ◽  
Madalina Filip ◽  
Alecu Aurel Ciorsac ◽  
Vasile Ostafe ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Glucocorticoid Receptors ◽  
Degradation Products ◽  
Organic Anion ◽  
Toxicity Tests ◽  
Medical Applications ◽  
Eye Injuries ◽  
Toxicological Effects

<p class="ADMETkeywordsheading">Polylactic acid (PLA) is a polymer with an increased potential to be used in different medical applications, including tissue engineering and drug-carries. The use of PLA in medical applications implies the evaluation of the human organism's response to the polymer inserting and to its degradation products. Consequently, within this study, we have investigated the solubility and ADMET profiles of the short oligomers (having the molecular weight lower than 3000 Da) resulting in degradation products of PLA. There is a linear decrease of the molar solubility of investigated oligomers with molecular weight. The results that are obtained also reveal that short oligomers of PLA have promising pharmacological profiles and limited toxicological effects on humans. These oligomers are predicted as potential inhibitors of the organic anion transporting peptides OATP1B1 and OATP1B3, they present minor probability to affect the androgen and glucocorticoid receptors, have a weak potential of hepatotoxicity, and may produce eye injuries. These outcomes may be used to guide or to supplement in vitro and/or in vivo toxicity tests such as to enhance the biodegradation properties of the biopolymer.</p>

scholarly journals A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7154
Author(s):  
Laura Schioppa ◽  
Fanta Fall ◽  
Sergio Ortiz ◽  
Jacques H. Poupaert ◽  
Joelle Quetin-Leclercq
Keyword(s):  
Medicinal Plants ◽  
Degradation Products ◽  
Biological Stability ◽  
Acidic Media ◽  
Microsomal Metabolism ◽  
Plasma Enzymes ◽  
Absorption Studies ◽  
H 30

Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters’ stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25–100 µg/mL) and plasma (LOQ: 5–125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, O-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability.

Differences between in vitro and in vivo degradation of LHRH by rat brain and other organs

1987 ◽  
Vol 253 (3) ◽  
pp. E317-E321 ◽  
Author(s):  
F. A. Carone ◽  
M. A. Stetler-Stevenson ◽  
V. May ◽  
A. LaBarbera ◽  
G. Flouret
Keyword(s):  
Degradation Products ◽  
Venous Blood ◽  
Simultaneous Action ◽  
Pituitary Cells ◽  
Time Intervals ◽  
Luteinizing Hormone Releasing Hormone ◽  
Hydrolysis Of ◽  
The Brain

Homogenates of brain, pituitary, liver, lung, ovary, and testes were incubated with [pyro Glu1-3,4-3H]luteinizing hormone-releasing hormone ([3H]LHRH), and the profiles of metabolites generated as a function of time were determined. After 5 min of incubation, 5 was the predominant metabolite in most homogenates. Although the profiles of metabolites varied at different time intervals, metabolites 2, 3, 4, and 5, and in some instances 7 and 9, appeared to form simultaneously and were detectable at 10 min. Neither metabolite 6 nor other larger metabolites formed initially as dominant degradation products. The findings suggest cleavage of LHRH by the simultaneous action of several endopeptidases. After a single vascular transit of [3H]LHRH, metabolites were determined in the venous blood of liver, lung, and brain of rats in vivo. There were no metabolites of [3H]LHRH in venous blood of liver and lung; however, metabolites 2-4 were present in venous blood of the brain. Incubation of rat anterior pituitary cells with [3H]LHRH yielded metabolites 1-4 but not metabolites 5 or 9 as in homogenates. Incubation of [3H]LHRH with porcine follicular granulosa cells resulted in the generation of metabolites 2-7 and 9, similar to the profile in homogenates. Thus, since homogenates contain enzymes of disrupted cells, they do not always reflect mechanisms for in vivo hydrolysis of circulating LHRH. Brain degraded 12.1% of LHRH during a single vascular transit and may account for substantial degradation of the circulating hormone.

scholarly journals Application of Probiotic Yeasts on Candida Species Associated Infection

2020 ◽  
Vol 6 (4) ◽  
pp. 189
Author(s):  
Lohith Kunyeit ◽  
Anu-Appaiah K A ◽  
Reeta P. Rao
Keyword(s):  
Combination Therapy ◽  
Candida Species ◽  
Short Chain Fatty Acids ◽  
Candida Auris ◽  
Protective Mechanisms ◽  
Probiotic Yeast ◽  
Life Threatening ◽  
Candida Infections

Superficial and life-threatening invasive Candida infections are a major clinical challenge in hospitalized and immuno-compromised patients. Emerging drug-resistance among Candida species is exacerbated by the limited availability of antifungals and their associated side-effects. In the current review, we discuss the application of probiotic yeasts as a potential alternative/ combination therapy against Candida infections. Preclinical studies have identified several probiotic yeasts that effectively inhibit virulence of Candida species, including Candida albicans, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida krusei and Candida auris. However, Saccharomyces cerevisiae var. boulardii is the only probiotic yeast commercially available. In addition, clinical studies have further confirmed the in vitro and in vivo activity of the probiotic yeasts against Candida species. Probiotics use a variety of protective mechanisms, including posing a physical barrier, the ability to aggregate pathogens and render them avirulent. Secreted metabolites such as short-chain fatty acids effectively inhibit the adhesion and morphological transition of Candida species. Overall, the probiotic yeasts could be a promising effective alternative or combination therapy for Candida infections. Additional studies would bolster the application of probiotic yeasts.

Cathepsin L mediates intracellular ileal digestion of gastric intrinsic factor

1995 ◽  
Vol 268 (1) ◽  
pp. G33-G40 ◽  
Author(s):  
M. M. Gordon ◽  
T. Howard ◽  
M. J. Becich ◽  
D. H. Alpers
Keyword(s):  
Degradation Products ◽  
Cathepsin L ◽  
Intrinsic Factor ◽  
Recombinant Baculovirus ◽  
Human Kidney ◽  
Intracellular Degradation ◽  
Basolateral Side ◽  
Renal Tubule Cell

Although acidic proteases of lysosomal origin are implicated in the degradation of intrinsic factor (IF) during cobalamin (cbl) transport across enterocytes and proximal renal tubule cell lines, the enzyme(s) involved in this process is not known. Recombinant (baculovirus-produced) rat 125I-labeled IF (125I-rIF), 43 kDa, added in vivo to the lumen of rat ileum was converted intracellularly to peptides of 33 and 26 kDa. In vitro rat 125I-rIF was degraded to peptides of 33 and 31 kDa by addition of cathepsin L; this conversion was fully inhibited by leupeptin. Western blot analysis using antiserum against denatured native rat IF identified additional cathepsin L degradation products in the 17- to 23-kDa range. In vitro the binding of cobalamin partially inhibited cathepsin L degradation of IF. Rat rIF produced from either insect (Sf9) or mammalian (CHO) cells and native rat IF were all degraded by cathepsin L, although the prominence of the various products differed in the recombinant preparations, being 33 and 36 kDa, respectively. Native rat IF was most sensitive to proteolysis, and no degradation products were identified. Rat 125I-rIF was taken up by LLC-PK1 cells, and 125I from degraded IF appeared abundantly on the basolateral side of cell monolayers by 1 h. The intracellular products of rat rIF in LLC-PK1 cells were the same size as those produced in vitro by the action of cathepsin L. Antiserum against a human kidney cDNA cathepsin L fusion protein easily demonstrated the protease in rat intestinal mucosa, as well as in all other tissues tested. These data suggest that cathepsin L is the protease responsible for the leupeptin-sensitive intracellular degradation of IF.

scholarly journals Pegylated megakaryocyte growth and development factor abrogates the lethal thrombocytopenia associated with carboplatin and irradiation in mice

Blood ◽  
1995 ◽  
Vol 86 (12) ◽  
pp. 4486-4492 ◽  
Author(s):  
MM Hokom ◽  
D Lacey ◽  
OB Kinstler ◽  
E Choi ◽  
S Kaufman ◽  
...  
Keyword(s):  
Growth And Development ◽  
Granulocyte Colony Stimulating Factor ◽  
Potent Inducer ◽  
Development Factor ◽  
Internal Bleeding ◽  
Life Threatening ◽  
Stimulating Factor ◽  
Sublethal Irradiation

Megakaryocyte growth and development factor (MGDF) is a potent inducer of megakaryopoiesis in vitro and thrombopoiesis in vivo. The effects of MGDF appear to be lineage-selective, making this cytokine an ideal candidate for use in alleviating clinically relevant thrombocytopenias. This report describes a murine model of life-threatening thrombocytopenia that results from the combination treatment of carboplatin and sublethal irradiation. Mortality of this regimen is 94% and is associated with widespread internal bleeding. The daily administration of pegylated recombinant human MGDF (PEG-rMGDF) significantly reduced mortality (to < 15%) and ameliorated the depth and duration of thrombocytopenia. The severity of leucopenia and anemia was also reduced, although it was not clear whether these effects were direct. Platelets generated in response to PEG-rMGDF were morphologically indistinguishable from normal platelets. PEG-rMGDF administered in combination with murine granulocyte colony-stimulating factor completely prevented mortality and further reduced leukopenia and thrombocytopenia. These data support the concept that PEG-rMGDF may be useful to treat iatrogenic thrombocytopenias.

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