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1.
Clin Appl Thromb Hemost ; 25: 1076029619840701, 2019.
Article in English | MEDLINE | ID: mdl-30987427

ABSTRACT

Heparin and its low-molecular-weight heparin derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications, including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine and less frequently bovine intestine and bovine lung. The worldwide dependence on the pig as a single dominant animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including the expanded use of bovine tissues. A number of laboratories are now also examining the similarities between heparin and low-molecular-weight heparins prepared from porcine and ovine tissues. This study was designed to compare low-molecular-weight heparin prepared from ovine heparin through chemical ß-elimination, a process currently used to prepare the low-molecular-weight heparin, enoxaparin. Using top-down, bottom-up, and compositional analyses as well as bioassays, low-molecular-weight heparin derived from ovine intestine was shown to closely resemble enoxaparin. Moreover, the compositions of daughter low-molecular-weight heparins prepared from three unfractionated ovine parent heparins were compared. Ovine enoxaparins had similar molecular weight and in vitro anticoagulant activities as Lovenox. Some disaccharide compositional, oligosaccharide composition at the reducing and nonreducing ends and intact chain compositional differences could be observed between porcine enoxaparin and ovine low-molecular-weight heparin. The similarity of these ovine and porcine heparin products suggests that their preclinical evaluation and ultimately clinical assessment is warranted.


Subject(s)
Anticoagulants/chemistry , Enoxaparin/chemistry , Heparin, Low-Molecular-Weight/chemistry , Animals , Anticoagulants/therapeutic use , Cattle , Enoxaparin/therapeutic use , Heparin, Low-Molecular-Weight/therapeutic use , Humans , Molecular Weight , Sheep , Swine , Venous Thromboembolism/drug therapy
2.
Clin Appl Thromb Hemost ; 23(6): 542-553, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28056526

ABSTRACT

Heparin and its low-molecular-weight heparin (LMWH) derivatives are widely used clinical anticoagulants. These drugs are critical for the practice of medicine in applications including kidney dialysis, cardiopulmonary bypass, and in the management of venous thromboembolism. Currently, these drugs are derived from livestock, primarily porcine intestine. The worldwide dependence on a single animal species has made the supply chain for this critical drug quite fragile, leading to the search for other sources of these drugs, including bovine tissues such as bovine intestine or lung. A number of laboratories are currently examining the similarities and differences between heparins prepared from porcine and bovine tissues. The current study is designed to compare LMWH prepared from bovine heparins through chemical ß-elimination, a process currently used to prepare the LMWH, enoxaparin, from porcine heparin. Using top-down, bottom-up, compositional analysis and bioassays, LMWHs, derived from bovine lung and intestine, are shown to closely resemble enoxaparin.


Subject(s)
Enoxaparin/standards , Heparin, Low-Molecular-Weight/standards , Animals , Anticoagulants/therapeutic use , Cattle , Clinical Laboratory Techniques , Heparin, Low-Molecular-Weight/therapeutic use , Intestines/chemistry , Lung/chemistry , Swine
3.
FEMS Microbiol Lett ; 339(1): 30-8, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23210909

ABSTRACT

The aim of this study was to evaluate the probiotic effects of Lactobacillus strains against Vibrio parahaemolyticus causing gastroenteritis. Six-week-old ICR mice were pretreated with four Lactobacillus strains at three dosages, and then challenged with V. parahaemolyticus TGqx01 (serotype O3:K6). The results showed that V. parahaemolyticus TGqx01 caused severe intestinal fluid accumulation (FA) and villi damage in control mice which were pretreated with phosphate-buffered saline. In contrast, significant alleviation of FA was seen in mice pretreated by with a high dose of Lactobacillus strains (P < 0.05, n = 6) but not in mice that received low-dose pretreatments. Among middle-dose treatments, two highly adhesive strains, Lactobacillus rhamnosus H15 and Lactobacillus brevis Y29-4, significantly decreased intestinal FA and villi damage in treated mice (P < 0.05). Two low-adhesive strains, Lactobacillus acidophilus Y14-3 and Lactobacillus fermentum F16-6, had no significant alleviating effects. At the same dosing levels, no significant differences in FA were observed in mice pretreated with strains with similar adhesive abilities but different antagonistic activities. Our findings suggest that Lactobacillus strains can alleviate V. parahaemolyticus-induced intestinal FA in mice, and the doses required for in vivo efficacy depend more on adhesive ability than on the antibacterial activity of strains.


Subject(s)
Lactobacillus/physiology , Probiotics , Vibrio Infections/microbiology , Vibrio parahaemolyticus/physiology , Analysis of Variance , Animals , Bacterial Adhesion/physiology , Disease Models, Animal , Female , Histocytochemistry , Intestinal Mucosa/pathology , Intestinal Secretions , Intestines/chemistry , Intestines/pathology , Male , Mice , Mice, Inbred ICR , Mucus/metabolism , Vibrio Infections/pathology , Vibrio Infections/therapy , Vibrio parahaemolyticus/pathogenicity
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