scholarly journals Leakage of Microbial Endotoxin through the Implant-Abutment Interface in Oral Implants: An In Vitro Study

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Rhoodie Garrana ◽  
Govindrau Mohangi ◽  
Paulo Malo ◽  
Miguel Nobre

Background. Endotoxin initiates osteoclastic activity resulting in bone loss. Endotoxin leakage through implant abutment connections negatively influences peri-implant bone levels.Objectives. (i) To determine if endotoxin can traverse different implant-abutment connection (IAC) designs; (ii) to quantify the amount of endotoxins traversing the IAC; (iii) to compare the in vitro comportments of different IACs.Materials and Methods. Twenty-seven IACs were inoculated withE. coliendotoxin. Six of the twenty-seven IACs were external connections from one system (Southern Implants) and the remaining twenty-one IACs were made up of seven internal IAC types from four different implant companies (Straumann, Ankylos, and Neodent, Southern Implants).Results. Of the 27 IACs tested, all 6 external IACs leaked measurable amounts of endotoxin. Of the remaining 21 internal IACs, 9 IACs did not show measurable leakage whilst the remaining 12 IACs leaked varying amounts. The mean log endotoxin level was significantly higher for the external compared to internal types (p=0.015).Conclusion. Within the parameters of this study, we can conclude that endotoxin leakage is dependent on the design of the IAC. Straumann Synocta, Straumann Cross-fit, and Ankylos displayed the best performances of all IACs tested with undetectable leakage after 7 days. Each of these IACs incorporated a morse-like component in their design. Speculation still exists over the impact of IAC endotoxin leakage on peri-implant tissues in vivo; hence, further investigations are required to further explore this.

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 473 ◽  
Author(s):  
Takuya Umehara ◽  
Saori Kosono ◽  
Dieter Söll ◽  
Koji Tamura

Protein lysine acetylation is a widely conserved posttranslational modification in all three domains of life. Lysine acetylation frequently occurs in aminoacyl-tRNA synthetases (aaRSs) from many organisms. In this study, we determined the impact of the naturally occurring acetylation at lysine-73 (K73) in Escherichia coli class II alanyl-tRNA synthetase (AlaRS) on its alanylation activity. We prepared an AlaRS K73Ac variant in which Nε-acetyl-l-lysine was incorporated at position 73 using an expanded genetic code system in E. coli. The AlaRS K73Ac variant showed low activity compared to the AlaRS wild type (WT). Nicotinamide treatment or CobB-deletion in an E. coli led to elevated acetylation levels of AlaRS K73Ac and strongly reduced alanylation activities. We assumed that alanylation by AlaRS is affected by K73 acetylation, and the modification is sensitive to CobB deacetylase in vivo. We also showed that E. coli expresses two CobB isoforms (CobB-L and CobB-S) in vivo. CobB-S displayed the deacetylase activity of the AlaRS K73Ac variant in vitro. Our results imply a potential regulatory role for lysine acetylation in controlling the activity of aaRSs and protein synthesis.


1997 ◽  
Vol 41 (1) ◽  
pp. 49-53 ◽  
Author(s):  
A Ahmed ◽  
M M París ◽  
M Trujillo ◽  
S M Hickey ◽  
L Wubbel ◽  
...  

In vitro and in vivo studies have demonstrated that the bacteriologic efficacy of once-daily aminoglycoside therapy is equivalent to that achieved with conventional multiple daily dosing. The impact of once-daily dosing for meningitis has not been studied. Using the well-characterized rabbit meningitis model, we compared two regimens of the same daily dosage of gentamicin given either once or in three divided doses for 24 or 72 h. The initial 1 h mean cerebrospinal fluid (CSF) gentamicin concentration for animals receiving a single dose (2.9 +/- 1.7 micrograms/ml) was threefold higher than that for the animals receiving multiple doses. The rate of bacterial killing in the first 8 h of treatment was significantly greater for the animals with higher concentrations in their CSF (-0.21 +/- 0.19 versus -0.03 +/- 0.22 log10 CFU/ml/h), suggesting concentration-dependent killing. By 24h, the mean reduction in bacterial titers was similar for the two regimens. In animals treated for 72 h, no differences in bactericidal activity was noted for 24, 48, or 72 h. Gentamicin at two different dosages was administered intracisternally to a separate set of animals to achieve considerably higher CSF gentamicin concentrations. In these animals, the rate of bacterial clearance in the first 8 h (0.52 +/- 0.15 and 0.58 +/- 0.15 log10 CFU/ml/h for the lower and higher dosages, respectively) was significantly greater than that in animals treated intravenously. In conclusion, there is evidence of concentration-dependent killing with gentamicin early in treatment for experimental E. coli meningitis, and once-daily dosing therapy appears to be at least as effective as multiple-dose therapy in reducing bacterial counts in CSF.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Furong Qiu ◽  
Jian Jiang ◽  
Yueming Ma ◽  
Guangji Wang ◽  
Chenglu Gao ◽  
...  

The aim of this study was to investigate the effect of single- and multidose administration of the ethanol extract of danshen on in vivo CYP3A activity in healthy volunteers. A sequential, open-label, and three-period pharmacokinetic interaction study design was used based on 12 healthy male individuals. The plasma concentrations of midazolam and its metabolite 1-hydroxymidazolam were measured. Treatment with single dose of the extract caused the meanCmaxof midazolam to increase by 87% compared with control. After 10 days of the danshen extract intake, the mean AUC0–12,Cmax, andt1/2of midazolam were decreased by 79.9%, 66.6%, and 43.8%, respectively. The mean clearance of midazolam was increased by 501.6% compared with control. The in vitro study showed that dihydrotanshinone I in the extract could inhibit CYP3A, while tanshinone IIA and cryptotanshinone could induce CYP3A. In conclusion, a single-dose administration of the danshen extract can inhibit intestinal CYP3A, but multidose administration can induce intestinal and hepatic CYP3A.


2017 ◽  
Vol 29 (6) ◽  
pp. 1169 ◽  
Author(s):  
Nicola A. Pascarelli ◽  
Antonella Fioravanti ◽  
Elena Moretti ◽  
Giacomo M. Guidelli ◽  
Lucia Mazzi ◽  
...  

Tumour necrosis factor (TNF)-α is primarily involved in the regulation of cell proliferation and apoptosis; in addition it possesses pro-inflammatory properties. Anti-TNF-α strategies involve either administration of anti-TNF-α antibody or soluble TNF receptor to mop up circulating TNF-α. Etanercept, a recombinant human TNF-α receptor, was found to be effective in the treatment of rheumatoid arthritis. The impact of TNF-α inhibitors on human fertility is of notable interest. This in vitro study investigated the effect of different concentrations of TNF-α and etanercept used alone or in combination on sperm viability, motility, mitochondrial function, percentage of apoptosis and chromatin integrity in swim-up selected human spermatozoa. A negative effect of TNF-α (300 and 500 ng mL–1) and etanercept (from 800 µg mL–1 to 2000 µg mL–1) individually on sperm viability, motility, mitochondrial function, percentage of apoptotic spermatozoa and sperm DNA integrity was demonstrated. However, at concentrations of 100 and 200 µg mL–1, etanercept can block, in a significant way, the toxic effects of TNF-α (500 ng mL–1) on studied sperm characteristics. Our results confirm that TNF-α has a detrimental effect on sperm function and suggest, for the first time, that etanercept may counteract the in vitro toxic action of TNF-α. This data appears to be quite promising, although further studies, both in vivo and in vitro, are needed to understand the exact mechanism of action of TNF-α and TNF-α antagonists on sperm function.


Perfusion ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 209-216 ◽  
Author(s):  
Samantha H Dallefeld ◽  
Jennifer Sherwin ◽  
Kanecia O Zimmerman ◽  
Kevin M Watt

Background: Dexmedetomidine is a sedative administered to minimize distress and decrease the risk of life threatening complications in children supported with extracorporeal membrane oxygenation. The extracorporeal membrane oxygenation circuit can extract drug and decrease drug exposure, placing the patient at risk of therapeutic failure. Objective: To determine the extraction of dexmedetomidine by the extracorporeal membrane oxygenation circuit. Materials and methods: Dexmedetomidine was studied in three closed-loop circuit configurations to isolate the impact of the oxygenator, hemofilter, and tubing on circuit extraction. Each circuit was primed with human blood according to standard practice for Duke Children’s Hospital, and flow was set to 1 L/min. Dexmedetomidine was dosed to achieve a therapeutic concentration of ~600 pg/mL. Dexmedetomidine was added to a separate tube of blood to serve as a control and evaluate for natural drug degradation. Serial blood samples were collected over 24 hours and concentrations were quantified with a validated assay. Drug recovery was calculated at each time point. Results: Dexmedetomidine was highly extracted by the oxygenator evidenced by a mean recovery of 62-67% at 4 hours and 23-34% at 24 hours in circuits with an oxygenator in-line. In contrast, mean recovery with the oxygenator removed was 96% at 4 hours and 93% at 24 hours. Dexmedetomidine was stable over time with a mean recovery in the control samples of 102% at 24 hours. Conclusion: These results suggest dexmedetomidine is extracted by the oxygenator in the extracorporeal membrane oxygenation circuit which may result in decreased drug exposure in vivo.


2008 ◽  
Vol 75 (4) ◽  
pp. 1074-1079 ◽  
Author(s):  
Natalie C. Berard ◽  
Richard A. Holley ◽  
Tim A. McAllister ◽  
Kim H. Ominski ◽  
Karin M. Wittenberg ◽  
...  

ABSTRACT There is a growing concern about the presence of pathogens in cattle manure and its implications on human and environmental health. The phytochemical-rich forage sainfoin (Onobrychis viciifolia) and purified phenolics (trans-cinnamic acid, p-coumaric acid, and ferulic acid) were evaluated for their ability to reduce the viability of pathogenic Escherichia coli strains, including E. coli O157:H7. MICs were determined using purified phenolics and acetone extracts of sainfoin and alfalfa (Medicago sativa), a non-tannin-containing legume. Ground sainfoin or pure phenolics were mixed with fresh cattle feces and inoculated with a ciprofloxacin-resistant strain of E. coli, O157:H7, to assess its viability at −20�C, 5�C, or 37�C over 14 days. Forty steers were fed either a sainfoin (hay or silage) or alfalfa (hay or silage) diet over a 9-week period. In the in vitro study, the MICs for coumaric (1.2 mg/ml) and cinnamic (1.4 mg/ml) acids were 10- to 20-fold lower than the MICs for sainfoin and alfalfa extracts. In the inoculated feces, the −20�C treatment had death rates which were at least twice as high as those of the 5�C treatment, irrespective of the additive used. Sainfoin was less effective than coumaric acid in reducing E. coli O157:H7 Cipr in the inoculated feces. During the animal trial, fecal E. coli numbers declined marginally in the presence of sainfoin (silage and hay) and alfalfa silage but not in the presence of hay, indicating the presence of other phenolics in alfalfa. In conclusion, phenolic-containing forages can be used as a means of minimally reducing E. coli shedding in cattle without affecting animal production.


2018 ◽  
Vol 19 (8) ◽  
pp. 2168 ◽  
Author(s):  
Sonja Heller ◽  
Gabriele Maurer ◽  
Christina Wanka ◽  
Ute Hofmann ◽  
Anna-Luisa Luger ◽  
...  

In several tumor entities, transketolase-like protein 1 (TKTL1) has been suggested to promote the nonoxidative part of the pentose phosphate pathway (PPP) and thereby to contribute to a malignant phenotype. However, its role in glioma biology has only been sparsely documented. In the present in vitro study using LNT-229 glioma cells, we analyzed the impact of TKTL1 gene suppression on basic metabolic parameters and on survival following oxygen restriction and ionizing radiation. TKTL1 was induced by hypoxia and by hypoxia-inducible factor-1α (HIF-1α). Knockdown of TKTL1 via shRNA increased the cells’ demand for glucose, decreased flux through the PPP and promoted cell death under hypoxic conditions. Following irradiation, suppression of TKTL1 expression resulted in elevated levels of reactive oxygen species (ROS) and reduced clonogenic survival. In summary, our results indicate a role of TKTL1 in the adaptation of tumor cells to oxygen deprivation and in the acquisition of radioresistance. Further studies are necessary to examine whether strategies that antagonize TKTL1 function will be able to restore the sensitivity of glioma cells towards irradiation and antiangiogenic therapies in the more complex in vivo environment.


2021 ◽  
Vol 8 (9) ◽  
pp. 197
Author(s):  
Gustav Bruer ◽  
Daria Gödecke ◽  
Manfred Kietzmann ◽  
Jessica Meißner

The effect of florfenicol against Escherichia coli (E. coli) was investigated in vivo to confirm results of an in vitro study of Bruer et al. (2019), which has shown positive effects of various antibacterial agents in combination with the antihistamine mepyramine (MEP). Therefore, pigs were treated in three different settings: An untreated control group, 10 mg/kg florfenicol (FFC) and 10 mg/kg FFC in combination with 20 mg/kg MEP. E. coli were isolated from faecal samples and analyzed in growth quantity and resistance to FFC. The FFC medication induced an increased number of resistant E. coli strains isolated from faecal samples. The number of colonies detected after cultivation of animal samples treated with 10 mg/kg FFC was higher than the number of colonies after treatment with 10 mg/kg FFC in combination with of FFC and MEP. Furthermore, the effect of both compounds was examined on bacterial susceptibility of Pasteurella multocida in vitro, where the combination of FFC with MEP resulted in a diminished minimum inhibitory concentration. We confirmed the development of bacterial resistance in the intestine as non-target tissue caused by the use of the antibacterial agent florfenicol. Moreover, the combination of FFC with an antihistamine like MEP offers a possibility to enhance the efficacy of an antibacterial treatment and modifies the effect on gut microbiota.


Author(s):  
Hervé Poilvache ◽  
Albert Ruiz-Sorribas ◽  
Olivier Cornu ◽  
Françoise Van Bambeke

Prosthetic Joint Infections (PJI) are frequent complications of arthroplasties. Their treatment is made complex by the rapid formation of bacterial biofilms, limiting the effectiveness of antibiotic therapy. In this study, we explore the effect of a tri-enzymatic cocktail (TEC) consisting of an endo-1,4-β-d-glucanase, a β-1,6-hexosaminidase, and an RNA/DNA nonspecific endonuclease combined with antibiotics of different classes against biofilms of S. aureus, S. epidermidis, and E. coli grown on Ti6Al4V substrates. Biofilms were grown in TSB with 10g/L glucose and 20g/L NaCl (TGN). Mature biofilms were assigned to a control group or treated with the TEC for 30 min, then either analyzed or reincubated for 24h in TGN or TGN with antibiotics. The cytotoxicity of the TEC was assayed against MG-63 osteoblasts, primary murine fibroblasts, and J-774 macrophages using the LDH release test. The TEC dispersed 80.3 to 95.2% of the biofilms’ biomass after 30 min. The reincubation of the treated biofilms with antibiotics resulted in a synergistic reduction of the total culturable bacterial count (CFU) compared to biofilms treated with antibiotics alone in the three tested species (additional reduction from 2 to more than 3 log10 CFU). No toxicity of the TEC was observed against the tested cell lines after a 24 h of incubation. The combination of pretreatment with TEC followed by a 24 h of incubation with antibiotics had a synergistic effect against biofilms of S. aureus, S. epidermidis, and E. coli. Further studies should assess the potential of the TEC as an adjuvant therapy in in vivo models of PJI.


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