Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli

Blood ◽  
2000 ◽  
Vol 95 (4) ◽  
pp. 1117-1123 ◽  
Author(s):  
M. C. Minnema ◽  
A. C. K. Chang ◽  
P. M. Jansen ◽  
Y. T. P. Lubbers ◽  
B. M. Pratt ◽  
...  

Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Escherichia coli infusion in baboons, but the mechanisms behind this effect are not clear. In the present study, we evaluated the effects of recombinant human ATIII (rhATIII) on the clinical course and the inflammatory cytokine and coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII starting 1 hour before an E colichallenge. Those in the control group were administered saline. Survival was significantly improved in the treatment group (P = .002). Both groups had similar hemodynamic responses to E coli challenge but different coagulation and inflammatory responses. The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls. In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons lethally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy.

Author(s):  
SUNARTI M.BIOMED ◽  
DEBORA PANINSARI

Objective: The objective of this study was to discover of the ethanolic extract of Rhinacanthus nasutus (L) Kurz in inhibiting Escherichia coli bacteria using an in vitro method. Methods: This is an experimental study using a laboratory test with Kirby-Bauer or paper disc method by observing and measuring the inhibition zone of the ethanolic extract of R. nasutus against E. coli bacteria with extract concentrations of 15%, 30%, and 60% consisting of control groups and treatment group. The positive control group used chloramphenicol antibiotics and negative control groups used Aquadest. E. coli was incubated at 37°C for 24 h. Then, the plates were incubated for 24 h at 37°C and the diameter of the inhibition zone was observed until the 3rd day with three repetitions. Results: The results of the study showed that the mean inhibition zone of E. coli bacteria was 10.93 mm, 12.09 mm, and 18.90 mm. The results of the Shapiro–Wilk test were p=0.199. The results of the one-way analysis of variance test were p<0.05 and that of the post hoc test indicated a significant value of p<0.05. Based on the results of the research, there were significant differences in the inhibition zone between the control group and the treatment group at a concentration of 15%, 30%, and 60%. Conclusion: R. nasutus extract was effective to inhibit the growth of E. coli bacteria at concentrations of 15%, 30%, and 60%, so R. nasutus is effective as an antimicrobial.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Gang Liu ◽  
Shuai Chen ◽  
Guiping Guan ◽  
Jun Tan ◽  
Naif A. Al-Dhabi ◽  
...  

This study aims to investigate the effects of dietary chitosan (COS) on gastrointestinal pathogen resistance in mice model. For two weeks, a control group of ICR mice received a basal diet whilst the intervention group received the basal diet supplemented with 300 mg/kg COS. After two weeks, the mice fed the supplemented diet had a lower body weight. Then enterotoxigenic Escherichia coli (E. coli) was administered to the mice through oral gavage, with each mouse receiving 108 CFU. At day 7 after infection, the bacterial load in the jejunum and faeces was significantly lower in the COS group than that in the control group. Moreover, the mRNA and protein levels of IL-1β, IL-6, IL-17, IL-18, and TNF-α were significantly lower in the group of mice receiving the COS diet; also the jejunal production of toll-like receptor-4 (TLR-4) was suppressed in the COS group. These results indicate the intervention influenced inflammation and controlled E. coli infection.


1991 ◽  
Vol 37 (3) ◽  
pp. 244-247 ◽  
Author(s):  
Koji Nomoto ◽  
Teruo Yokokura ◽  
Yasunobu Yoshikai ◽  
Masao Mitsuyama ◽  
Kikuo Nomoto

A single administration of fluorouracil (5-FU), a well-used cancer chemotherapeutic agent, at high doses (338–800 mg/kg) to specific pathogen free mice induced a lethal infection with Escherichia coli. The infection was manifested in all the mice treated with 5-FU 7–14 days after administration of the drug, when the number of E. coli in liver reached levels ranging from 108 to 1010 colony-forming units, and the type of the infecting bacteria was limited to E. coli. The infection was accompanied with the increase in the population levels of E. coli in the intestinal tract which reached levels about 103 to 104 times as high as those of normal mice. Administration of tegafur, a less toxic derivative of 5-FU, to mice at a lethal dose of 1280 mg/kg induced infection with E. coli similar to that induced by 5-FU. Multiple administration of both streptomycin sulfate and cephalothin to mice after treatment with 5-FU protected the mice completely from the lethal infection induced by 5-FU, suggesting that the lethality of 5-FU was due to the indigenous bacterial infection. Key words: fluorouracil, Escherichia coli, mice, indigenous infection.


Author(s):  
Yin Qu ◽  
Zhijun Zhang ◽  
Yafeng Lu ◽  
De Zheng ◽  
Wei Yang

Background: Anal fistula is one of the most common colorectal and perirectal diseases in the world. Cuyuxunxi (CYXX) prescription is an efficient herbal fumigant used to promote the surgical wound healing of anal fistulas. Objective: This study aimed to explore the underlying molecular mechanism of CYXX prescription on surgical wound healing of anal fistulas. Methods: Ten patients with anal fistula were randomized into a control group or treatment group. The wound surface of patients in the control group was rinsed by normal saline, while that in the treatment group was rinsed by CYXX prescription. The wound tissues of patients with anal fistulas seven days after the surgery were collected for hematoxylin-eosin (HE) staining and RNA sequencing. The expressions of differentially expressed genes (DEGs) were validated by real-time quantitative PCR (RT-qPCR). Results: HE staining showed that CYXX treatment reduced the infiltration of inflammatory cells. A total of 472 DEGs, including 141 up-regulated genes and 331 down-regulated genes, were identified. These genes were significantly related to skin development, xenobiotic stimulus, and inflammation. In addition, the consistency rate of RT-qPCR and sequencing results was 83.33%, which showed a high relative reliability of the sequencing results. Conclusion: CYXX prescription could improve epidermis repair and reduce inflammatory responses.


2020 ◽  
Vol 13 (3) ◽  
pp. 46
Author(s):  
Tiago Fonseca Silva ◽  
José Robson Neves Cavalcanti Filho ◽  
Mariana Mirelle Lima Barreto Fonsêca ◽  
Natalia Medeiros dos Santos ◽  
Ana Carolina Barbosa da Silva ◽  
...  

The relevance of oxidative stress in the pathogenesis of several diseases (including inflammatory disorders) has traditionally led to the search for new sources of antioxidant compounds. In this work, we report the selection of fractions with high antioxidant action from B. tetraphylla (BT) leaf extracts. In vitro methods (DPPH and ABTS assays; determination of phenolic and flavonoid contents) were used to select products derived from B. tetraphylla with high antioxidant action. Then, the samples with the highest potentials were evaluated in a model of injury based on the inoculation of a lethal dose of heat-inactivated Escherichia coli in Tenebrio molitor larvae. Due to its higher antioxidant properties, the methanolic extract (BTME) was chosen to be fractionated using Sephadex LH-20 column-based chromatography. Two fractions from BTME (BTFC and BTFD) were the most active fractions. Pre-treatment with these fractions protected larvae of T. molitor from the stress induced by inoculation of heat-inactivated E. coli. Similarly, BTFC and BTFD increased the lifespan of larvae infected with a lethal dose of enteroaggregative E. coli 042. NMR data indicated the presence of aliphatic compounds (terpenes, fatty acids, carbohydrates) and aromatic compounds (phenolic compounds). These findings suggested that products derived from B. tetraphylla leaves are promising candidates for the development of antioxidant and anti-infective agents able to treat oxidative-related dysfunctions.


2012 ◽  
Vol 19 (5) ◽  
pp. 740-745 ◽  
Author(s):  
André A. Grassmann ◽  
Samuel R. Félix ◽  
Carolina Ximendes dos Santos ◽  
Marta G. Amaral ◽  
Amilton C. P. Seixas Neto ◽  
...  

ABSTRACTLeptospirosis, a worldwide zoonosis, lacks an effective, safe, and cross-protective vaccine. LipL32, the most abundant, immunogenic, and conserved surface lipoprotein present in all pathogenic species ofLeptospira, is a promising antigen candidate for a recombinant vaccine. However, several studies have reported a lack of protection when this protein is used as a subunit vaccine. In an attempt to enhance the immune response, we used LipL32 coupled to or coadministered with the B subunit of theEscherichia coliheat-labile enterotoxin (LTB) in a hamster model of leptospirosis. After homologous challenge with 5× the 50% lethal dose (LD50) ofLeptospira interrogans, animals vaccinated with LipL32 coadministered with LTB and LTB::LipL32 had significantly higher survival rates (P< 0.05) than animals from the control group. This is the first report of a protective immune response afforded by a subunit vaccine using LipL32 and represents an important contribution toward the development of improved leptospirosis vaccines.


2016 ◽  
Vol 101 (7-8) ◽  
pp. 304-312 ◽  
Author(s):  
Cagla Bali ◽  
Nejat Altintas ◽  
Ozlem Ozmete ◽  
Ibrahim Gelincik ◽  
Hakan Yabanoglu ◽  
...  

Curcumin has remarkable anti-inflammatory and antioxidant properties. The aim of this study was to investigate the protective effects of curcumin on a rat model of carbapenem-resistant Escherichia coli–induced acute lung injury (ALI). Thirty-two rats were randomly allocated to 4 groups to induce an ALI: negative control group (rats not infected with E coli with no antibiotic treatment), positive control group (rats infected with E coli with no antibiotic treatment), imipenem group (rats infected with E coli that received intraperitoneal injection of imipenem), and the imipenem+curcumin group (rats infected with E coli that received intraperitoneal injection of imipenem and were fed on curcumin).The rats were killed, and lung tissues samples were harvested for biochemical analyses and histopathologic examination. Total antioxidant status (TAS), total oxidant status (TOS), tumor necrosis factor α (TNFα), and interleukin-6 (IL6) were measured. TOS increased in the positive control group (P &lt; 0.001) and decreased in the imipenem and imipenem+curcumin groups (P &lt; 0.001 and P &lt; 0.001, respectively). TAS decreased in the positive control group (P = 0.005). Imipenem treatment did not increase TAS, but the imipenem+curcumin group increased TAS (P = 0.014). TNFα and IL6 increased in the positive control group compared with the negative control group (P &lt; 0.001 and P = 0.010, respectively). Imipenem decreased TNFα (P &lt; 0.001), but did not decrease IL6 (P = 0.418). Imipenem+curcumin decreased TNFα (P &lt; 0.001); this decrease was more pronounced compared with the imipenem group (P = 0.008). IL6 decreased in the curcumin group compared with the positive control group (P = 0.011). Curcumin combined with imipenem can be an alternative therapeutic agent to overcome the resistance of E coli strains.


2018 ◽  
Vol 19 (2) ◽  
pp. 196
Author(s):  
Maria Fatima Palupi ◽  
Hera Maheshwari ◽  
Huda Salahuddin Darusman ◽  
Etih Sudarnika ◽  
I Wayan Teguh Wibawan

Colistin sulphate is the ultimate antimicrobial choice for the treatment of multidrug resistance gram negative bacteria infections with in human. The purposes of this study were to detect the presence of colistin resistant E. coli and mcr-1 gene in broiler and to transfer the mcr-1 gene to Salmonella enteritidis ATCC 13076. A total of 54 one day old broilers were divided into three groups that consists of 18 chicks broiler per group and raised up to 40 days old. The first group was used as control. The first treatment group was given colistin sulphate 5 ìg/g feed for 40 days and broilers in second treatment group was given 80.000 IU/kg body weight for first three days. Swab cloaca samples were taken every 10 days from each broiler. At age 40 days all chickens were slaughtered and meat samples were collected. Samples of cloacal swabs, fresh and cooked meat were examined for the presence of colistin resistant E. coli and mcr-1 gene. Susceptibility to colistin sulfate was conducted by agar dilution method, and detection of mcr-1 gene was conducted using polymerase chain reaction. The results showed that no colistin resistant E. coli was detected in the control group. Colistin resistant E. coli (27.78%) and mcr-1 gene (20.00%) were detected in animals in the first treatment group, respectively. Whilst 11.11% colistin resistant E. coli and 5.56% were carriying mcr-1 gene in the second treatment group. Colistin resistant E. coli were found 5.56% from raw meat samples and 3.70% had mcr-1 gene. Transfer of mcr-1 gene from colistin resistant E. coli to Salmonella enteritidis ATCC 13076 was success. These results showed the necessity of limitation usage of colistin sulphate in food animal. 


2014 ◽  
Vol 17 (4) ◽  
pp. 657-664 ◽  
Author(s):  
P. Brodzki ◽  
M. Bochniarz ◽  
A. Brodzki ◽  
Z. Wrona ◽  
W. Wawron

AbstractThe aim of this study was to determine the percentage of participation of particular species of microorganisms, isolated from the uterus of cows with endometritis and from cows without inflammatory lesions of the uterus, in the same postpartum period. The aim of the study was also to examine how long after parturition non-treated endometritis persists. Moreover, antibiotic susceptibility tests were carried out of the bacterial isolates dominating in the uterus. Forty cows were included in the study: 20 cows with endometritis (experimental group) and 20 cows without any inflammatory condition of the uterus (control group). The material for cytological and bacteriological tests was collected on the 5th, 26th, 40thand 60thday after parturition, using an intrauterine brush adapted for cows. The total number of collected isolates was 149, including 120 isolates from the uterus of cows with endometritis and 29 isolates from the uterus of cows without endometritis. The following species of microorganisms were isolated from the material collected from cows with endometritis: T. pyogenes (49.2%), E.coli (22.5%), F. necrophorum (11.7%), Staphylococcus sp. (6.7%), B. melaninogenicus (5.8%), and Streptococcus sp. (4.1%). The participation percentage of particular species of bacteria in the material collected from the uterus of cows without endometritis was as follows: T. pyogenes (27.6%), E.coli (24.2%), Staphylococcus sp. (20.7%), Streptococcus sp. (20.7%), B. melaninogenicus (3.4%) and F. necrophorum (3.4%). The highest percentage of T. pyogenes isolates was susceptible to ceftiofur (89.6%); cefoperazone (85.1%) and amoxicillin combined with clavulanic acid (79.1%). E. coli isolates were most susceptible to amoxicillin combined with clavulanic acid (100%), cefoperazone (94.1%) and oxytetracycline (82.3%).


2016 ◽  
Vol 84 (5) ◽  
pp. 1633-1641 ◽  
Author(s):  
Nandakumar Packiriswamy ◽  
Michael Steury ◽  
Ian C. McCabe ◽  
Scott D. Fitzgerald ◽  
Narayanan Parameswaran

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase previously shown to mediate polymicrobial sepsis-induced inflammation. The goal of the present study was to examine the role of GRK5 in monomicrobial pulmonary infection by using an intratrachealEscherichia coliinfection model of pneumonia. We used sublethal and lethal doses ofE. colito examine the mechanistic differences between low-grade and high-grade inflammation induced byE. coliinfection. With a sublethal dose ofE. coli, GRK5 knockout (KO) mice exhibited higher plasma CXCL1/KC levels and enhanced lung neutrophil recruitment early after infection, and lower bacterial loads, than wild-type (WT) mice. The inflammatory response was also diminished, and resolution of inflammation advanced, in the lungs of GRK5 KO mice. In contrast to the reduced bacterial loads in GRK5 KO mice following a sublethal dose, at a lethal dose ofE. coli, the bacterial burdens remained high in GRK5 KO mice relative to those in WT mice. This occurred in spite of enhanced plasma CXCL1 levels as well as neutrophil recruitment in the KO mice. But the recruited neutrophils (following high-dose infection) exhibited decreased CD11b expression and reduced reactive oxygen species production, suggesting decreased neutrophil activation or increased neutrophil exhaustion in the GRK5 KO mice. In agreement with the increased bacterial burden, KO mice showed poorer survival than WT mice followingE. coliinfection at a lethal dose. Overall, our data suggest that GRK5 negatively regulates CXCL1/KC levels during bacterial pneumonia but that the role of GRK5 in the clinical outcome in this model is dependent on the bacterial dose.


Sign in / Sign up

Export Citation Format

Share Document