scholarly journals Potential of Molecular Weight and Structure of Tannins to Reduce Methane Emissions from Ruminants: A Review

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 856 ◽  
Author(s):  
Isaac A. Aboagye ◽  
Karen A. Beauchemin
Keyword(s):  
Molecular Weight ◽  
Environmental Sustainability ◽  
Production Systems ◽  
Condensed Tannin ◽  
In Vivo Studies ◽  
Animal Performance ◽  
Terrestrial Plants ◽  
Rumen Microbes ◽  
Ch4 Production

There is a need to reduce enteric methane (CH4) to ensure the environmental sustainability of ruminant production systems. Tannins are naturally found in both tropical and temperate plants, and have been shown to consistently decrease urinary nitrogen (N) excretion when consumed by ruminants. However, the limited number of in vivo studies conducted indicates that the effects of tannins on intake, digestibility, rumen fermentation, CH4 production and animal performance vary depending on source, type, dose, and molecular weight (MW). There are two main types of tannin in terrestrial plants: condensed tannin (CT; high MW) and hydrolysable tannin (HT; low MW). Consumption of CT and HT by ruminants can reduce N excretion without negatively affecting animal performance. High MW tannins bind to dietary protein, while low MW tannins affect rumen microbes, and thus, irrespective of type of tannin, N excretion is affected. The structure of high MW tannin is more diverse compared with that of low MW tannin, which may partly explain the inconsistent effects of CT on CH4 production reported in in vivo studies. In contrast, the limited number of in vivo studies with low MW HT potentially shows a consistent decrease in CH4 production, possibly attributed to the gallic acid subunit. Further in vivo studies are needed to determine the effects of tannins, characterized by MW and structural composition, on reducing CH4 emissions and improving animal performance in ruminants.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue I. Effects of Heparin Fractions

1981 ◽  
Vol 46 (03) ◽  
pp. 612-616 ◽  
Author(s):  
U Schmitz-Huebner ◽  
L Balleisen ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Molecular Weight ◽  
Day Treatment ◽  
Gel Filtration ◽  
Weight Fraction ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Platelet Factor ◽  
Heparin Fractions

SummaryHigh and low molecular weight heparin fractions obtained by gel filtration chromatography of sodium mucosal heparin were injected subcutaneously into six healthy volunteers and compared with the unfractionated substance in a cross-over trial. Equal doses of 5,000 U were administered twice daily over a period of three days and heparin activity was repeatedly controlled before and 2, 4, 8 hrs after injection by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of subcutaneously administered fractionated heparin on platelet function was examined on three of the volunteers. The results show that s.c. injections of the low molecular weight fraction induced markedly higher anti-Xa activity than injections of the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the high molecular weight fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA production, while the low molecular weight fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of platelet Factor 4 in plasma. During the three-day treatment periods, no side-effects and no significant changes in the response to heparin injections were detected.

scholarly journals Low Molecular Weight Hydroxyethyl Chitosan-Prednisolone Conjugate for Renal Targeting Therapy: Synthesis, Characterization and In Vivo Studies

Theranostics ◽  
2012 ◽  
Vol 2 (11) ◽  
pp. 1054-1063 ◽  
Author(s):  
Xia-kai He ◽  
Zhi-xiang Yuan ◽  
Xiao-juan Wu ◽  
Chao-qun Xu ◽  
Wan-yu Li
Keyword(s):  
Molecular Weight ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Targeting Therapy

In Vivo Studies On The Inhibition Of Coagulation By Fractionated Heparin

1981 ◽  
Author(s):  
U Schmitz-Huebner ◽  
L Balleisen ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Gel Filtration ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Chromogenic Substrate ◽  
Serotonin Content ◽  
Heparin Activity ◽  
Heparin Fractions

Recent investigations suggest that low molecular weight heparin may have advantages over conventional heparin with regard to the prevention of venous thrombosis and haemorrhagic side effects.High (HMW) and low (LMW) molecular weight heparin fractions with mean MWs of 16,000 and 8,800 respectively, obtained by gel filtration chromatography of sodium mucosal heparin (B. Braun Melsungen), were injected subcutaneously into six volunteers and compared with the unfractionated substance in a cross-over trial. Doses of 5,000 U were administered twice daily over a period of three days and heparin activity was controlled before injection and 2,4,8 hours afterwards by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of fractionated heparin on platelet function was examined. The results show that the LMW fraction induced markedly higher anti-Xa activity than the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the HMW fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA-production, while the LMW fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of PF IV, whereas the serotonin content of platelets determined at the same time increased.It is concluded that s.c. injections of LMW heparin induce relatively high levels of anti-Xa activity without leading to sensitive platelet activation or to major effects on overall clotting tests.

scholarly journals Glycosylation and functionality of recombinant β-glucocerebrosidase from various production systems

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Yoram Tekoah ◽  
Salit Tzaban ◽  
Tali Kizhner ◽  
Mariana Hainrichson ◽  
Anna Gantman ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Production Systems ◽  
In Vivo Studies ◽  
Target Cells ◽  
Enzyme Replacement ◽  
Target Organs ◽  
Key Factor ◽  
Cell Stability ◽  
Mannose Receptors

The glycosylation of recombinant β-glucocerebrosidase, and in particular the exposure of mannose residues, has been shown to be a key factor in the success of ERT (enzyme replacement therapy) for the treatment of GD (Gaucher disease). Macrophages, the target cells in GD, internalize β-glucocerebrosidase through MRs (mannose receptors). Three enzymes are commercially available for the treatment of GD by ERT. Taliglucerase alfa, imiglucerase and velaglucerase alfa are each produced in different cell systems and undergo various post-translational or post-production glycosylation modifications to expose their mannose residues. This is the first study in which the glycosylation profiles of the three enzymes are compared, using the same methodology and the effect on functionality and cellular uptake is evaluated. While the major differences in glycosylation profiles reside in the variation of terminal residues and mannose chain length, the enzymatic activity and stability are not affected by these differences. Furthermore, the cellular uptake and in-cell stability in rat and human macrophages are similar. Finally, in vivo studies to evaluate the uptake into target organs also show similar results for all three enzymes. These results indicate that the variations of glycosylation between the three regulatory-approved β-glucocerebrosidase enzymes have no effect on their function or distribution.

scholarly journals Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1437
Author(s):  
Olga A. Sindeeva ◽  
Ekaterina S. Prikhozhdenko ◽  
Igor Schurov ◽  
Nikolay Sedykh ◽  
Sergey Goriainov ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Granulation Tissue ◽  
Sodium Succinate ◽  
Mechanical Damage ◽  
Film Coating ◽  
In Vivo Studies ◽  
Metallic Stent ◽  
Tracheal Mucosa ◽  
Drug Eluting

Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating.

scholarly journals Low-Molecular-Weight Fucoidan as Complementary Therapy of Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer

2021 ◽  
Author(s):  
Ching-Wen Huang ◽  
Yen-Cheng Chen ◽  
Tzu-Chieh Yin ◽  
Po-Jung Chen ◽  
Tsung-Kun Chang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Molecular Weight ◽  
Cell Viability ◽  
Signaling Pathway ◽  
Complementary Therapy ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Tumor Cell Migration ◽  
Anti Cancer

This study investigated the roles of low-molecular-weight fucoidan (LMWF) in enhancing the anti-cancer effects of fluoropyrimidine-based chemotherapy. HCT116 and Caco-2 cells were treated with LMWF and 5-FU. Cell viability, cell cycle, apoptosis, and migration were analyzed in both cell types. Potential mechanisms underlying how LMWF enhances the anti-cancer effects of fluoropyrimidine-based chemotherapy were also explored. The cell viability of HCT116 and Caco-2 cells was significantly reduced after treatment with a LMWF-5-FU combination. In HCT116 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through the 1) induction of cell cycle arrest in the S phase and 2) late apoptosis mediated by the Jun-N-terminal kinase (JNK) signaling pathway. In Caco-2 cells, LMWF enhanced the suppressive effects of 5-FU on cell viability through both c-mesenchymal&ndash;epithelial transition (MET)/ Kirsten Rat Sarcoma virus (KRAS)/ extracellular signal-regulated kinase (ERK) and c-MET/ phosphatidyl-inositol 3-kinases (PI3K)/ protein kinase B (AKT) signaling pathways. Moreover, LMWF enhanced the suppressive effects of 5-FU on tumor cell migration through the c-MET/ matrix metalloproteinase (MMP)-2 signaling pathway in both HCT116 and Caco-2 cells. Our results demonstrated that LMWF is a potential complementary therapy for enhancing the efficacies of fluoropyrimidine-based chemotherapy in colorectal cancers (CRCs) with the wild-type or mutated KRAS gene through different mechanisms. However, in vivo studies and in clinical trials are required to validate the results of the present study.

scholarly journals Comparative Studies on the Anticoagulant Profile of Branded Enoxaparin and a New Biosimilar Version

2020 ◽  
Vol 26 ◽  
pp. 107602962096082
Author(s):  
Dalia Qneibi ◽  
Eduardo Ramacciotti ◽  
Ariane Scarlatelli Macedo ◽  
Roberto Augusto Caffaro ◽  
Leandro Barile Agati ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Performance ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Factor Xa ◽  
In Vivo Studies ◽  
In Vitro Tests ◽  
Thrombin Time

Low molecular weight heparins (LMWH) represent depolymerized heparin prepared by various methods that exhibit differential, biochemical and pharmacological profiles. Enoxaparin is prepared by benzylation followed by alkaline depolymerization of porcine heparin. Upon the expiration of its patent, several biosimilar versions of enoxaparin have become available. Heparinox (Sodic enoxaparine; Cristália Produtos Químicos Farmacêuticos LTDA, Sao Paulo, Brazil) is a new biosimilar form of enoxaparin. We assessed the molecular weight and the biochemical profile of Heparinox and compared its properties to the original branded enoxaparin (Lovenox; Sanofi, Paris, France). Clotting profiles compared included activated clotting time, activated partial thromboplastin time (aPTT), and thrombin time (TT). Anti-protease assays included anti-factor Xa and anti-factor IIa activities. Thrombin generation was measured using a calibrated automated thrombogram and thrombokinetic profile included peak thrombin, lag time and area under the curve. USP potency was determined using commercially available assay kits. Molecular weight profiling was determined using high performance liquid chromatography. We determined that Heparinox and Lovenox were comparable in their molecular weight profile. Th anticoagulant profile of the branded and biosimilar version were also similar in the clot based aPTT and TT. Similarly, the anti-Xa and anti-IIa activities were comparable in the products. No differences were noted in the thrombin generation inhibitory profile of the branded and biosimilar versions of enoxaparin. Our studies suggest that Heparinox is bioequivalent to the original branded enoxaparin based upon in vitro tests however will require further in vivo studies in animal models and humans to determine their clinical bioequivalence.

scholarly journals High Molecular Weight Hyaluronan Suppresses Macrophage M1 Polarization and Enhances IL-10 Production in PM2.5-Induced Lung Inflammation

Molecules ◽  
2019 ◽  
Vol 24 (9) ◽  
pp. 1766 ◽  
Author(s):  
Qiwen Shi ◽  
Lan Zhao ◽  
Chenming Xu ◽  
Leifang Zhang ◽  
Hang Zhao
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Lung Inflammation ◽  
Macrophage Polarization ◽  
Pulmonary Inflammation ◽  
In Vivo Studies ◽  
Protective Effects ◽  
M1 Polarization

PM2.5 is particulate matter with a diameter of 2.5 μm or less. Airway macrophages are the key players regulating PM2.5-induced inflammation. High molecular weight hyaluronan (HMW-HA) has previously been shown to exert protective effects on PM2.5-induced acute lung injury and inflammation. However, little is known about the detailed mechanism. In this study, we aimed to determine whether HMW-HA alleviates PM2.5-induced pulmonary inflammation by modulating macrophage polarization. The levels of M1 biomarkers TNF-α, IL-1β, IL-6, CXCL1, CXCL2, NOS2 and CD86, as well as M2 biomarkers IL-10, MRC1, and Arg-1 produced by macrophages were measured by ELISA, qPCR, and flow cytometry. In addition, the amount of M1 macrophages in lung tissues was examined by immunofluorescence of CD68 and NOS2. We observed a decline in PM2.5-induced M1 polarization both in macrophages and lung tissues when HMW-HA was administered simultaneously. Meanwhile, western blot analysis revealed that PM2.5-induced JNK and p38 phosphorylation was suppressed by HMW-HA. Furthermore, in vitro and in vivo studies showed that co-stimulation with HMW-HA and PM2.5 promoted the expression and release of IL-10, but exhibited limited effects on the transcription of MRC1 and ARG1. In conclusion, our results demonstrated that HMW-HA ameliorates PM2.5-induced lung inflammation by repressing M1 polarization through JNK and p38 pathways and promoting the production of pro-resolving cytokine IL-10.

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