scholarly journals Potent anti-edematous and protective effects of ciprofloxacin in pulmonary ricinosis

2016 ◽  
pp. AAC.01696-16 ◽  
Author(s):  
Yoav Gal ◽  
Anita Sapoznikov ◽  
Reut Falach ◽  
Sharon Ehrlich ◽  
Moshe Aftalion ◽  
...  
Keyword(s):  
Pulmonary Inflammation ◽  
Lethal Dose ◽  
Neutrophil Migration ◽  
Lung Damage ◽  
Protective Effects ◽  
Plant Toxin ◽  
Antibody Treatment ◽  
Inflammatory Cytokine Production ◽  
Pulmonary Exposure ◽  
Efficient Protection

The plant-toxin ricin, is considered a biological threat agent of concern and is most toxic when inhaled. Pulmonary exposure to a lethal dose of ricin can be redressed by treatment with anti-ricin antibodies, however late antitoxin intervention is of limited efficacy. This limitation is associated with the overt lung damage, clinically manifested as severe pulmonary inflammation, which develops over time. Increased evidence indicates that ciprofloxacin, a broad spectrum anti-microbial agent, possesses immunomodulatory properties. Here we demonstrate, that while anti-ricin antibody administration at late hours after intranasal exposure to ricin confers limited protection to mice, highly efficient protection can be achieved by adding ciprofloxacin to the antibody treatment. We further demonstrate that parameters associated with lung injury, in particular pulmonary pro-inflammatory cytokine production, neutrophil migration and edema, are sharply reduced in ricin-intoxicated mice that were treated with ciprofloxacin. Presented data highlights the potential clinical application of ciprofloxacin as a beneficial immunomodulatory agent in the course of ricin intoxication.

scholarly journals Acute vaping exacerbates microbial pneumonia due to calcium (Ca2+) dysregulation

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256166
Author(s):  
Rui Zhang ◽  
Myles M. Jones ◽  
De’Jana Parker ◽  
Ronna E. Dornsife ◽  
Nathan Wymer ◽  
...  
Keyword(s):  
Pulmonary Inflammation ◽  
Airway Epithelial Cells ◽  
Lung Pathology ◽  
Airway Epithelial ◽  
Microbial Infection ◽  
Inflammatory Cytokine Production ◽  
Pulmonary Exposure ◽  
Lung Histology ◽  
Macrophage Chemotaxis

As electronic cigarette (E-cig) use, also known as “vaping”, has rapidly increased in popularity, data regarding potential pathologic effects are recently emerging. Recent associations between vaping and lung pathology have led to an increased need to scrutinize E-cigs for adverse health impacts. Our previous work (and others) has associated vaping with Ca2+-dependent cytotoxicity in cultured human airway epithelial cells. Herein, we develop a vaped e-liquid pulmonary exposure mouse model to evaluate vaping effects in vivo. Using this model, we demonstrate lung pathology through the use of preclinical measures, that is, the lung wet: dry ratio and lung histology/H&E staining. Further, we demonstrate that acute vaping increases macrophage chemotaxis, which was ascertained using flow cytometry-based techniques, and inflammatory cytokine production, via Luminex analysis, through a Ca2+-dependent mechanism. This increase in macrophage activation appears to exacerbate pulmonary pathology resulting from microbial infection. Importantly, modulating Ca2+ signaling may present a therapeutic direction for treatment against vaping-associated pulmonary inflammation.

scholarly journals Prostaglandin E2Receptor Antagonist with Antimicrobial Activity against Methicillin-ResistantStaphylococcus aureus

2017 ◽  
Vol 62 (3) ◽  
Author(s):  
Mélanie A. C. Ikeh ◽  
Paul L. Fidel ◽  
Mairi C. Noverr
Keyword(s):  
Antimicrobial Activity ◽  
Receptor Antagonist ◽  
Enzyme Inhibitors ◽  
Lethal Dose ◽  
Prostaglandin E ◽  
Protective Effects ◽  
Physiological Concentration ◽  
Content Type ◽  
Abdominal Infections

ABSTRACTPolymicrobial intra-abdominal infections (IAI) involvingCandida albicansandStaphylococcus aureusare associated with severe morbidity and mortality (∼80%). Our laboratory discovered that the immunomodulatory eicosanoid prostaglandin E2(PGE2) plays a key role in the lethal inflammatory response during polymicrobial IAI using a mouse model of infection. In studies designed to uncover key PGE2biosynthesis/signaling components involved in the response, selective eicosanoid enzyme inhibitors and receptor antagonists were selected and prescreened for antimicrobial activity againstC. albicansorS. aureus. Unexpectedly, we found that the EP4receptor antagonist L-161,982 had direct growth-inhibitory effects onS. aureusin vitroat the physiological concentration required to block the PGE2interaction with EP4. This antimicrobial activity was observed with methicillin-sensitiveS. aureusand methicillin-resistantS. aureus(MRSA) strains, with the MIC and minimum bactericidal concentration values for planktonic cells being 50 μg/ml and 100 μg/ml, respectively. In addition, L-161,982 inhibitedS. aureusbiofilm formation and had activity against preformed mature biofilms. More importantly, treatment of mice with L-161,982 following intraperitoneal inoculation with a lethal dose of MRSA significantly reduced the bioburden and enhanced survival. Furthermore, L-161,982 protected mice against the synergistic lethality induced by coinfection withC. albicansandS. aureus. The antimicrobial activity of L-161,982 is independent of EP4receptor inhibitory activity; an alternative EP4receptor antagonist exerted no antimicrobial or protective effects. Taken together, these findings demonstrate that L-161,982 has potent antimicrobial activity against MRSA and may represent a significant therapeutic alternative in improving the prognosis of mono- or polymicrobial infections involving MRSA.

Alveolar macrophages: novel therapeutic targets for respiratory diseases

2021 ◽  
Vol 23 ◽  
Author(s):  
Pamelia N. Lim ◽  
Maritza M. Cervantes ◽  
Linh K. Pham ◽  
Alissa C. Rothchild
Keyword(s):  
Alveolar Macrophages ◽  
Respiratory Diseases ◽  
Severe Disease ◽  
Pulmonary Inflammation ◽  
Therapeutic Targets ◽  
Therapeutic Strategies ◽  
Lung Damage ◽  
Respiratory Pathogens ◽  
Inhaled Antibiotics ◽  
Potential Risks

Abstract Alveolar macrophages (AMs) are lung-resident myeloid cells that sit at the interface of the airway and lung tissue. Under homeostatic conditions, their primary function is to clear debris, dead cells and excess surfactant from the airways. They also serve as innate pulmonary sentinels for respiratory pathogens and environmental airborne particles and as regulators of pulmonary inflammation. However, they have not typically been viewed as primary therapeutic targets for respiratory diseases. Here, we discuss the role of AMs in various lung diseases, explore the potential therapeutic strategies to target these innate cells and weigh the potential risks and challenges of such therapies. Additionally, in the context of the COVID-19 pandemic, we examine the role AMs play in severe disease and the therapeutic strategies that have been harnessed to modulate their function and protect against severe lung damage. There are many novel approaches in development to target AMs, such as inhaled antibiotics, liposomal and microparticle delivery systems, and host-directed therapies, which have the potential to provide critical treatment to patients suffering from severe respiratory diseases, yet there is still much work to be done to fully understand the possible benefits and risks of such approaches.

scholarly journals Protective Effects of Isoflurane Pretreatment in Endotoxin-induced Lung Injury

2006 ◽  
Vol 104 (3) ◽  
pp. 511-517 ◽  
Author(s):  
Jörg Reutershan ◽  
Daniel Chang ◽  
John K. Hayes ◽  
Klaus Ley
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Neutrophil Migration ◽  
Neutrophil Recruitment ◽  
Pulmonary Vasculature ◽  
Lung Edema ◽  
Protective Effects ◽  
Protein Leakage ◽  
Endotoxin Exposure ◽  
Organ Systems

Background The concept of antiinflammatory effects of volatile anesthetics is well established in vitro and in some organ systems. Their protective role in lung injury, however, remains to be elucidated. The authors hypothesized that in the lung, isoflurane pretreatment may attenuate neutrophil infiltration and reduce endotoxin-induced injury. Methods Male C57Bl/6 mice were exposed to aerosolized lipopolysaccharide. Neutrophil recruitment into the pulmonary vasculature and migration into the different lung compartments (interstitium and alveolar air space) were determined by flow cytometry. Capillary protein leakage, formation of lung edema, and concentration of the chemokines keratinocyte-derived chemokine (CXCL1) and macrophage inflammatory protein 2 (CXCL2/3) in bronchoalveolar lavage were compared in mice with or without isoflurane treatment (1.4% inspired for 30 min) at different times before and after endotoxin exposure. Results Endotoxin inhalation induced significant neutrophil migration into all lung compartments. Isoflurane pretreatment attenuated both neutrophil recruitment into lung interstitium and alveolar space when given 1 or 12 h before or 1 h after lipopolysaccharide but not at 4, 6, or 24 h before endotoxin exposure. Isoflurane pretreatment 1 or 12 h before lipopolysaccharide also reduced protein leakage and pulmonary edema. Production of CXCL1 and CXCL2/3 in the bronchoalveolar lavage was reduced when isoflurane was given 1 h but not 12 h before lipopolysaccharide, suggesting different mechanisms for early and late protection. Conclusion Isoflurane pretreatment reduces acute lung injury when given 1 or 12 h before an endotoxin challenge or within the first hour of an already established inflammation.

scholarly journals Protective Effects of Flavonoid and Polyphenol from Lotus Leaf on Lung Damage Induced by Inhalation of N2O4 in mice

2021 ◽  
Vol 233 ◽  
pp. 02013
Author(s):  
Wenjun Li ◽  
Ning Xu ◽  
Yong Hu ◽  
Zhijie Liu ◽  
Wei Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Damage Model ◽  
Physiological Saline ◽  
Normal Group ◽  
Lung Damage ◽  
Protective Effects ◽  
Male Mice ◽  
Lotus Leaf ◽  
Animal Damage ◽  
Mda Content

To study the protective effects of flavonoid and polyphenol (FP) from lotus leaf on the damage induced by N2O4 in mice. Constructing an animal damage model through exposing mice to 45μl N2O4 in a 120 L sealed cabinet for 30 minutes. ICR male mice were randomly divided into normal group, physiological saline+N2O4 group,1.25g/kgFP +N2O4 group, 2.50g/kgFP + N2O4 group, 3.75g/kg FP +N2O4 group. 1.25, 2.50, 3.75 g/kg FP were orally administered to mice respectively for 5 days, equal volume physiological saline for normal group and physiological saline+N2O4 group. Then, the three FP groups and the physiological saline+N2O4 group were exposed to N2O4 in the cabinet on 5th day. In an hour after N2O4 exposure, killing the mice by dislocation to measure the SOD, GSH-Px activity and MDA content in lung tissue, checking pathology change in lung tissue slice. Results were shown: the 1.25, 2.50g/kg FP increased SOD (U/mg pro) by 30.3% and 24.4%, GSH-Px (U/mg pro) by 77.4% and 60.9%, respectively. Pathological observation of lung tissue showed that three FP groups had lighter damage than the physiological saline+N2O4 group. So, FP has significant protective effects on damage caused by N2O4 in mice.

scholarly journals Toxicity of pristine and paint-embedded TiO2 nanomaterials

2018 ◽  
Vol 38 (1) ◽  
pp. 11-24 ◽  
Author(s):  
AT Saber ◽  
A Mortensen ◽  
J Szarek ◽  
NR Jacobsen ◽  
M Levin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Titanium Dioxide ◽  
Single Dose ◽  
Pulmonary Inflammation ◽  
Similar Type ◽  
Liver Histology ◽  
Pulmonary Exposure ◽  
Phase Inclusion ◽  
Different Types ◽  
Tio2 Nanomaterials

Little is known on the toxicity of nanomaterials in the user phase. Inclusion of nanomaterials in paints is a common nanotechnology application. This study focuses on the toxicity of dusts from sanding of paints containing nanomaterials. We compared the toxicity of titanium dioxide nanomaterials (TiO2NMs) and dusts generated by sanding boards coated with paints with different amounts of two different types of uncoated TiO2NMs (diameters:10.5 nm and 38 nm). Mice were intratracheally instilled with a single dose of 18, 54 and 162 µg of TiO2NMs or 54, 162 and 486 µg of sanding dusts. At 1, 3 and 28 days post-instillation, we evaluated pulmonary inflammation, liver histology and DNA damage in lung and liver. Pulmonary exposure to both pristine TiO2NMs and sanding dusts with different types of TiO2NMs resulted in dose-dependently increased influx of neutrophils into the lung lumen. There was no difference between the sanding dusts from the two paints. For all exposures but not in vehicle controls, mild histological lesions were observed in the liver. Pulmonary exposure to pristine TiO2NMs and paint dusts with TiO2NMs caused similar type of histological lesions in the liver.

A novel pneumococcal protein–polysaccharide conjugate vaccine based on biotin–streptavidin

2021 ◽  
Author(s):  
Mengze Guo ◽  
Xiaonan Guo ◽  
Chenxing Zhang ◽  
Shidong Zhu ◽  
Yue Zhang ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Conjugate Vaccine ◽  
Capsular Polysaccharide ◽  
Lethal Dose ◽  
Public Health Problem ◽  
Protective Effects ◽  
Covalent Interaction ◽  
Pathogen Elimination ◽  
Type Iv ◽  
Wide Range

Pneumococcal disease is a serious public health problem worldwide and an important cause of morbidity and mortality among children and adults in developing countries. Although vaccination is among the most effective approaches to prevent and control pneumococcal diseases, approved vaccines have limited protective effects. We developed a pneumococcal protein–polysaccharide conjugate vaccine that is mediated by the non-covalent interaction between biotin and streptavidin. Biotinylated type IV capsular polysaccharide was incubated with a fusion protein containing core streptavidin and Streptococcus pneumoniae virulence protein and relying on the non-covalent interaction between biotin and streptavidin to prepare the protein–polysaccharide conjugate vaccine. Analysis of vaccine efficacy revealed that mice immunized with the protein–polysaccharide conjugate vaccine produced antibodies with high potency against virulence proteins and polysaccharide antigens and were able to induce Th1 and Th17 responses. The antibodies identified using an opsonophagocytic assay were capable of activating the complement system and promoting pathogen elimination by phagocytes. Additionally, mice immunized with the protein–polysaccharide conjugate vaccine and then infected with a lethal dose of Streptococcus pneumoniae demonstrated induced protective immunity. The data indicated that the pneumococcal protein–polysaccharide (biotin–streptavidin) conjugate vaccine demonstrated broad-spectrum activity applicable to a wide range of people and ease of direct coupling between protein and polysaccharide. These findings provide further evidence for the application of biotin–streptavidin in S. pneumoniae vaccines.

Protective effects of hydrogen against irradiation

2021 ◽  
Vol 27 ◽  
Author(s):  
Yasuhiro Terasaki ◽  
Mika Terasaki ◽  
Akira Shimizu
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Cultured Cells ◽  
Animal Experiments ◽  
Lung Epithelial Cells ◽  
Lung Damage ◽  
Protective Effects ◽  
Chronic Radiation ◽  
Radiation Induced ◽  
Reactive Oxidants

: Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2 , O2•− , ONOO− , and •OH. Molecular hydrogen (H2 ) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO− , and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2 -enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances of in the treatment of H2 as a new class of radioprotective agents.

scholarly journals Protective effects of zingerone derivate on ionizing radiation-induced intestinal injury

2019 ◽  
Vol 60 (6) ◽  
pp. 740-746 ◽  
Author(s):  
Jing Wu ◽  
Yuqing Duan ◽  
Jie Cui ◽  
Yinping Dong ◽  
Hongyan Li ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Morphological Changes ◽  
Lethal Dose ◽  
Intestinal Injury ◽  
Intestinal Morphology ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Intestinal Crypt ◽  
Proliferation And Differentiation ◽  
Crypt Cells

Abstract Intestinal injury is the primary toxicity of radiotherapy for pelvic and abdominal tumors, and it is also one of the common acute complications of radiotherapy. At present, there are no effective drugs to prevent intestinal injury in the clinic. Zingerone is a natural product with radioprotective effects. In this study, a novel compound (thiazolidine hydrochloride, TZC01) was synthesized by structural modification of zingerone. The effects of TZC01 on preventing intestinal injury from radiation were further investigated in this study. C57BL/6N mice were exposed to a lethal dose of abdominal irradiation (ABI) with and without TZC01 treatments. The morphological changes of the intestine and various makers of intestinal crypt cells were investigated. Treatment with TZC01 improved the survival rate of mice exposed to 12 Gy ABI. Moreover, TZC01 protected the intestinal morphology of mice, decreased the apoptotic rate of intestinal crypt cells, maintained cell regeneration and promoted crypt cell proliferation and differentiation. This study suggests that TZC01 has preventive and therapeutic effects on radiation enteritis by promoting the proliferation and differentiation of crypt cells to protect the small intestine from the toxic effects of ionizing radiation. Furthermore, the study of TCZ01 lays a strong foundation for developing novel radioprotectors with multiple properties.

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