• Title, Summary, Keyword: animal model of sepsis

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Coupling killing to neutralization: combined therapy with ceftriaxone/Pep19-2.5 counteracts sepsis in rabbits

  • Barcena-Varela, Sergio;Martinez-de-Tejada, Guillermo;Martin, Lukas;Schuerholz, Tobias;Gil-Royo, Ana Gloria;Fukuoka, Satoshi;Goldmann, Torsten;Droemann, Daniel;Correa, Wilmar;Gutsmann, Thomas;Brandenburg, Klaus;Heinbockel, Lena
    • Experimental and Molecular Medicine
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    • v.49 no.6
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    • pp.1.1-1.9
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    • 2017
  • Sepsis, which is induced by severe bacterial infections, is a major cause of death worldwide, and therapies combating the disease are urgently needed. Because many drugs have failed in clinical trials despite their efficacy in mouse models, the development of reliable animal models of sepsis is in great demand. Several studies have suggested that rabbits reflect sepsis-related symptoms more accurately than mice. In this study, we evaluated a rabbit model of acute sepsis caused by the intravenous inoculation of Salmonella enterica. The model reproduces numerous symptoms characteristic of human sepsis including hyperlactatemia, hyperglycemia, leukopenia, hypothermia and the hyperproduction of several pro-inflammatory cytokines. Hence, it was chosen to investigate the proposed ability of Pep19-2.5-an anti-endotoxic peptide with high affinity to lipopolysaccharide and lipoprotein-to attenuate sepsis-associated pathologies in combination with an antibiotic (ceftriaxone). We demonstrate that a combination of Pep19-2.5 and ceftriaxone administered intravenously to the rabbits (1) kills bacteria and eliminates bacteremia 30 min post challenge; (2) inhibits Toll-like receptor 4 agonists in serum 90 min post challenge; (3) reduces serum levels of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor ${\alpha}$); and (4) reverts to hypothermia and gives rise to temperature values indistinguishable from basal levels 330 min post challenge. The two components of the combination displayed synergism in some of these activities, and Pep19-2.5 notably counteracted the endotoxin-inducing potential of ceftriaxone. Thus, the combination therapy of Pep19-2.5 and ceftriaxone holds promise as a candidate for human sepsis therapy.

Altered Expression of Peroxiredoxin and Thioredoxin in Septic Animal Model (패혈증 동물 모델에서 Peroxiredoxin 및 Thioredoxin의 발현 변화)

  • Kim, Hyung-Jung;Chae, Ho-Zoon;Ahn, Chul-Min;Kim, Sung-Kyu;Lee, Won-Young
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.4
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    • pp.451-459
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    • 1999
  • Background : In sepsis, excessive generation of reactive oxygen species plays key roles in the pathogenesis of acute lung injury. The serum antioxidants such as catalase and MnSOD are elevated in sepsis and considered as predictors of acute respiratory distress syndrome(ARDS) and prognostic factors of sepsis. Peroxiredoxin(Prx) has recently been known as an unique and major intracellular antioxidant. In this study, we evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells(RAW 267.7) after treatment of oxidative stress and endotoxin and measured the amount of Prx I, Prx II and thioredoxin(Trx) in peritoneal and bronchoalveolar lavage fluid of septic animal model. Methods : Using immunoblot analysis with specific antibodies against Prx I, Prx II and Trx, we evaluated the distribution of Prx I and Prx II in human neutrophil, alveolar macrophage and red blood cell. We evaluated the expression of Prx I and Prx II in mouse monocyte-macrophage cells after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide(LPS) and measured the amount of Prx I, Prx II and Trx in peritoneal lavage fluid of intraperitoneal septic animals(septic animal model induced with intraperitoneal 6 mg/Kg LPS injection) and those in bronchoalveolar lavage fluid of intraperitoneal septic animals and intravenous septic animals(septic animal model induced with intravenous 5 mg/Kg LPS injection) and compared with the severity of lung inflammation. Results : The distribution of Prx I and Prx II were so different among human neutrophil, alveolar macrophage and red blood cell. The expression of Prx I in mouse monocyte-macrophage cells was increased after treatment of $5\;{\mu}M$ menadione and $1\;{\mu}g/ml$ lipopolysaccharide but that of Prx II was not increased. The amount of Prx I, Prx II and Trx were increased in peritoneal lavage fluid of intraperitoneal septic animals but were not increased in bronchoalveolar lavage fluid of intraperitoneal and intravenous septic animals regardless of the severity of lung inflammation. Conclusion : As intracellular antioxidant, the expression of Prx I is increased in mouse monocyte-macrophage cells after treatment of oxidative stress and endotoxin. The amount of Prx I, Prx II and Trx are increased in local inflammatory site but not increased in injured lung of septic animal model.

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Pathophysiology of Oral Mucositis induced by Anticancer Therapy (항암치료 후 발생하는 구강 점막염의 병태생리)

  • Yoon, Jung-Hoon;Choj, Jong-Hoon
    • Journal of Oral Medicine and Pain
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    • v.25 no.4
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    • pp.365-369
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    • 2000
  • Oral mucositis or stomatitis produced by stomatotoxic chemotherapy and/or radiation therapy are painful, restrict oral intake and, importantly, act as sites of secondary infection and potals of entry for the endogenous oral microflora often leading to bacteremias or sepsis. A number of clinical observations and studies of animal model suggests a pathophysiological complexity in the development of mucositis. The condition appears to represent a sequential interaction of the oral mucosal cells and tissues, pro-inflammatory cytokines, and local environmental factors in the mouth. This article discussed and reviewed biological process of the mucositis and, the role of cytokines as initiators and amplifiers of the process. The recognition that the pathophysiology of mucositis is a multifactorial process has presented opportunities for intervention based upon biological attenuation.

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In Vitro and In Vivo Anti-Oxidative and Anti-Inflammatory Activities of Acer tegmentosum Maxim Extracts (RAW 264.7 대식세포와 염증유도 동물모델에서 산겨릅나무 추출물의 항산화 및 항염증 효과)

  • Lee, Cho-Eun;Jeong, Hyeon-Hee;Cho, Jin-Ah;Ly, Sun Yung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.1
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    • pp.1-9
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    • 2017
  • Acer tegmentosum Maxim (ATM) is known as traditional medicine for treatment of hepatic disorders such as hepatitis, related-inflammatory disease, and hepatic cancer. In this study, we evaluated the antioxidant and anti-inflammatory effects of ATM extracted with $80^{\circ}C$ water or 95% ethanol. Antioxidant activities of ATM extracts were measured based on DPPH and ABTS radical scavenging activities, total polyphenolic compound contents, and ferric reducing antioxidant power. The anti-inflammatory effects of ATM extract were assayed on release of nitric oxide, tumor necrosis factor $(TNF)-{\alpha}$, and interferon $(IFN)-{\gamma}$ from lipopolysaccharide (LPS)-induced macrophages. In these experiments, 95% ethanol extract of ATM showed stronger antioxidant and anti-inflammatory effects than water extract. Therefore, we determined the effects of ATM ethanol extract on an animal model of sepsis. Seven days oral gavage of ATM ethanol extract followed by LPS stimulation reduced the protein levels of $TNF-{\alpha}$ and $IFN-{\gamma}$ in serum as well as mRNA levels of $TNF-{\alpha}$ and interleukin-6 in intestinal epithelial cells. In addition, ATM ethanol extract reduced DNA damage in mouse lymphocytes. These results indicate that ATM extract has strong antioxidant and anti-inflammatory in vitro and in vivo effects and may be developed as a potential food material for prevention of inflammatory diseases.

Multimodal Imaging of Sarcopenia using Optical Coherence Tomography and Ultrasound in Rat Model

  • Jeon, Byeong Hwan;Chae, Yu-Gyeong;Hwang, Sang Seok;Kim, Dong Kyu;Oak, Chulho;Park, Eun-Kee;Ahn, Yeh-Chan
    • Journal of the Optical Society of Korea
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    • v.18 no.1
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    • pp.55-59
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    • 2014
  • Sarcopenia, or reduced muscle mass and volume, is due to various factors such as senile change, neuronal degeneration, drug, malignancy, and sepsis. Sarcopenia with the aging process has been evidenced by the decline in muscle mass by 0.5 to 1% per year with 3-5% reduction in muscle strength for 10 years between the ages of 40 and 50, and a 1-2% of decline of mass every year in people aged 60-70. Therefore, early diagnosis and understanding the mechanism of sarcopenia are crucial in the prevention of muscle loss. However, it is still difficult to image changes of muscle microstructure due to a lack of techniques. In this study, we developed an animal model using denervated rats to induce a rapid atrophy in the tibialis anterior (TA) and imaged its structural changes using optical coherence tomography (OCT) along with histologic and ultrasound analyses. Ultrasound showed changes of overall muscle size. Histology revealed that the atrophic TA muscle displayed an increased size variability of muscle fiber and inflammatory changes. Three dimensional OCT imaged the changes of perimysial grid and muscle fiber structure in real time without sacrifice. These observed advantages of multimodal imaging using OCT and ultrasound would provide clinical benefits in the diagnosis of sarcopenia.