scholarly journals Impact of Cytokines and Phosphoproteins in Response to Chronic Joint Infection

Biology ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 167
Author(s):  
Nicole Prince ◽  
Julia A. Penatzer ◽  
Matthew J. Dietz ◽  
Jonathan W. Boyd
Keyword(s):  
Chronic Inflammation ◽  
Cellular Response ◽  
Joint Infection ◽  
Acute Infection ◽  
Network Centrality ◽  
Chronic Infections ◽  
Aseptic Inflammation ◽  
Total Knee ◽  
Ifn Γ ◽  
The Impact

The early cellular response to infection has been investigated extensively, generating valuable information regarding the mediators of acute infection response. Various cytokines have been highlighted for their critical roles, and the actions of these cytokines are related to intracellular phosphorylation changes to promote infection resolution. However, the development of chronic infections has not been thoroughly investigated. While it is known that wound healing processes are disrupted, the interactions of cytokines and phosphoproteins that contribute to this dysregulation are not well understood. To investigate these relationships, this study used a network centrality approach to assess the impact of individual cytokines and phosphoproteins during chronic inflammation and infection. Tissues were taken from patients undergoing total knee arthroplasty (TKA) and total knee revision (TKR) procedures across two tissue depths to understand which proteins are contributing most to the dysregulation observed at the joint. Notably, p-c-Jun, p-CREB, p-BAD, IL-10, IL-12p70, IL-13, and IFN-γ contributed highly to the network of proteins involved in aseptic inflammation caused by implants. Similarly, p-PTEN, IL-4, IL-10, IL-13, IFN-γ, and TNF-α appear to be central to signaling disruptions observed in septic joints. Ultimately, the network centrality approach provided insight into the altered tissue responses observed in chronic inflammation and infection.

scholarly journals The Impact of use of Double Set-up on Infection Rates in Revision Total Knee Replacement and Limb Salvage Procedures

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jennifer Waterman ◽  
Jon Minter ◽  
Paul Ghattas ◽  
Brandon Green
Keyword(s):  
Limb Salvage ◽  
Recent Literature ◽  
Joint Infection ◽  
Recurrent Infection ◽  
Revision Total Knee Arthroplasty ◽  
Infection Rates ◽  
Revision Total Knee Replacement ◽  
Total Knee ◽  
Set Up ◽  
The Impact

A retrospective analysis was performed to determine the impact of utilizing a double set-up procedure on reducing infection rates revision total knee and limb salvage procedures in patients with known joint infection.  Eighteen cases fit selection criteria.  The recurrence rate of infection was 5.5% which is less than reported recent literature review.   This suggests the use of a double set-up in combination with other infection reducing protocols may help further reduce recurrent infection. Keywords: double set-up, infection, revision total knee arthroplasty, limb-salvage

scholarly journals Involvement of Host Defense Mechanisms against Toxoplasma gondii Infection in Anhedonic and Despair-Like Behaviors in Mice

2017 ◽  
Vol 85 (4) ◽  
Author(s):  
Motamed Elsayed Mahmoud ◽  
Ragab Fereig ◽  
Yoshifumi Nishikawa
Keyword(s):  
Toxoplasma Gondii ◽  
Host Defense ◽  
Defense Mechanisms ◽  
Defense Mechanism ◽  
Acute Infection ◽  
Sickness Behavior ◽  
Wild Type ◽  
Chronic Infections ◽  
Content Type ◽  
Ifn Γ

ABSTRACT Toxoplasma gondii is a pathogen relevant to psychiatric disorders. We recently showed that reactivation of chronic T. gondii infection induced depression-like behaviors in mice. Furthermore, it has been hypothesized that depression-like behaviors are mediated via a host defense mechanism against invading pathogens; proximate mechanisms of this behavioral hypothesis remain unclear. In the present study, we investigate the contribution of indoleamine 2,3-dioxygenase (IDO), inflammation, and interferon gamma (IFN-γ) to anhedonic and despair-related behaviors in T. gondii-infected mice by using sucrose preference and forced-swim tests, respectively. First, we confirmed that BALB/c mice exhibited both sickness and depression-like behaviors during acute infection. Treatment of infected wild-type mice with minocycline (anti-inflammatory drug) abated sickness and anhedonic and despair-like behaviors, whereas in T. gondii-infected mice, treatment normalized kynurenine/tryptophan (Kyn/Trp) ratios in both plasma and brain tissue. Additionally, T. gondii infection failed to induce anhedonic and despair-like behaviors or increase the Kyn/Trp ratio in immunocompromised (IFN-γ−/−) mice, whereas sickness behavior was observed in both immunocompetent and IFN-γ−/− mice following infection. Furthermore, treatment with 1-methyl tryptophan (an IDO inhibitor) did not affect locomotor activity, attenuated clinical scores and anhedonic and despair-like behaviors, and resulted in normal Kyn/Trp ratios in T. gondii-infected wild-type mice. Although low levels of serotonin and dopamine were observed in the brain during acute and chronic infections, anhedonic and despair-like behaviors were not detected in the chronic stage of infection. Collectively, our results demonstrated that immune enhancement in response to infection with T. gondii resulted in IFN-γ production, IDO activation, and inflammation associated with anhedonic and despair-like behaviors.

scholarly journals High throughput screen identifies IFN-γ-dependent inhibitors of Toxoplasma gondii growth

2018 ◽  
Author(s):  
Joshua B. Radke ◽  
Kimberly L. Carey ◽  
Subrata Shaw ◽  
Shailesh R. Metkar ◽  
Carol Mulrooney ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
High Throughput ◽  
Severe Disease ◽  
Acute Infection ◽  
Congenital Infection ◽  
Host Cells ◽  
High Throughput Screen ◽  
Chronic Infections ◽  
Ifn Γ

AbstractToxoplasma gondii is an obligate intracellular parasite capable of causing severe disease due to congenital infection and in patients with compromised immune systems. Control of infection is dependent on a robust Th1 type immune response including production of interferon gamma (IFN-γ), which is essential for control. IFN-γ activates a variety of anti-microbial mechanisms in host cells, which are then able to control intracellular parasites such as T. gondii. Despite the effectiveness of these pathways in controlling acute infection, the immune system is unable to eradicate chronic infections that can persist for life. Similarly, while antibiotic treatment can control acute infection, it is unable to eliminate chronic infection. To identify compounds that would act synergistically with IFN-γ, we performed a high-throughput screen of diverse small molecule libraries to identify inhibitors of T. gondii. We identified a number of compounds that inhibited parasite growth in vitro at low μM concentrations and that demonstrated enhanced potency in the presence of low level of IFN-γ. A subset of these compounds act by enhancing the recruitment of LC3 to the parasite-containing vacuole, suggesting they work by an autophagy-related process, while others were independent of this pathway. The pattern of IFN-γ-dependence was shared among the majority of analogs from 6 priority scaffolds and analysis of structure activity relationships for one such class revealed specific stereochemistry associated with this feature. Identification of these IFN-γ-dependent leads may lead to development of improved therapeutics due to their synergistic interactions with immune responses.

Results of debridement, antibiotics, and implant retention for periprosthetic knee joint infection supplemented with the use of intraosseous antibiotics

2021 ◽  
Vol 103-B (6 Supple A) ◽  
pp. 185-190
Author(s):  
Beau J. Kildow ◽  
Shaun P. Patel ◽  
Jesse E. Otero ◽  
Keith A. Fehring ◽  
Brian M. Curtin ◽  
...  
Keyword(s):  
Joint Infection ◽  
Acute Infection ◽  
Clinical Signs ◽  
Case Series ◽  
Antibiotic Administration ◽  
Chronic Infections ◽  
Musculoskeletal Infection ◽  
Local Bone ◽  
Implant Retention

Aims Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190.

Early outcomes of a modern cemented total knee arthroplasty

2021 ◽  
Vol 103-B (6 Supple A) ◽  
pp. 51-58
Author(s):  
JaeWon Yang ◽  
Nathanael D. Heckmann ◽  
Cindy R. Nahhas ◽  
Michael B. Salzano ◽  
Gregory P. Ruzich ◽  
...  
Keyword(s):  
Total Knee Arthroplasty ◽  
Aseptic Loosening ◽  
Knee Arthroplasty ◽  
Joint Infection ◽  
Posterior Stabilized ◽  
Cruciate Retaining ◽  
Primary Tkas ◽  
Total Knee ◽  
The Impact

Aims Recent total knee arthroplasty (TKA) designs have featured more anatomical morphologies and shorter tibial keels. However, several reports have raised concerns about the impact of these modifications on implant longevity. The aim of this study was to report the early performance of a modern, cemented TKA design. Methods All patients who received a primary, cemented TKA between 2012 and 2017 with a minimum two-year follow-up were included. The implant investigated features an asymmetrical tibial baseplate and shortened keel. Patient demographic details, Knee Society Scores (KSS), component alignment, and the presence of radiolucent lines at final follow-up were recorded. Kaplan-Meier analyses were performed to estimate survivorship. Results A total of 720 of 754 primary TKAs (95.5%) were included with a mean follow-up of 3.9 years (SD 1.3); 562 (78.1%) were cruciate-retaining and 158 (21.9%) were posterior-stabilized. A total of 11 (1.5%) required reoperation for periprosthetic joint infection and seven (1.0%) for aseptic tibial loosening (five cruciate-retaining, two posterior-stabilized). Loosening occurred at a mean of 3.3 years (0.9 to 6.5). There were no cases of loosening in the 33 patients who received a 14 mm × 30 mm tibial stem extension. All-cause survivorship was 96.6% at three years (95% confidence interval (CI) 95.3% to 98.0%) and 96.2% at five years (95% CI 94.8% to 97.7%). Survivorship with revision for aseptic loosening was 99.6% at three years (95% CI 99.1% to 100.0%) and 99.1% at five years (95% CI 98.4% to 99.9%). Tibial components were in significantly more varus in those with aseptic loosening (mean 3.4° (SD 3.7°) vs 1.3° (SD 2.0°); p = 0.015). There were no other differences in demographic, radiological, or surgical characteristics between revised and non-revised TKAs for aseptic loosening (p = 0.293 to 1.00). Mean KSS improved significantly from 57.3 (SD 9.5) preoperatively to 92.6 (SD 8.9) at the final follow-up (p < 0.001). Conclusion This is the largest series to date of this design of implant. At short-term follow-up, the rate of aseptic tibial loosening is not overly concerning. Further observation is required to determine if there will be an abnormal rate of loosening at mid- to long-term follow-up. Cite this article: Bone Joint J 2021;103-B(6 Supple A):51–58.

scholarly journals ‘Liver let die’: oxidative DNA damage and hepatotropic viruses

2014 ◽  
Vol 95 (5) ◽  
pp. 991-1004 ◽  
Author(s):  
Martin R. Higgs ◽  
Philippe Chouteau ◽  
Hervé Lerat
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cellular Response ◽  
Oxidative Dna Damage ◽  
Molecular Mechanisms ◽  
Large Body ◽  
Clinical Importance ◽  
Dna Lesions ◽  
Chronic Infections ◽  
The Impact

Chronic infections by the hepatotropic viruses hepatitis B virus (HBV) and hepatitis C virus (HCV) are major risk factors for the development of hepatocellular carcinoma (HCC). It is estimated that more than 700 000 individuals per year die from HCC, and around 80 % of HCC is attributable to HBV or HCV infection. Despite the clear clinical importance of virus-associated HCC, the underlying molecular mechanisms remain largely elusive. Oxidative stress, in particular DNA lesions associated with oxidative damage, play a major contributory role in carcinogenesis, and are strongly linked to the development of many cancers, including HCC. A large body of evidence demonstrates that both HBV and HCV induce hepatic oxidative stress, with increased oxidative DNA damage being observed both in infected individuals and in murine models of infection. Here, we review the impact of HBV and HCV on the incidence and repair of oxidative DNA damage. We begin by giving a brief overview of oxidative stress and the repair of DNA lesions induced by oxidative stress. We then review in detail the evidence surrounding the mechanisms by which both viruses stimulate oxidative stress, before focusing on how the viral proteins themselves may perturb the cellular response to oxidative DNA damage, impacting upon genome stability and thus hepatocarcinogenesis.

The impact of Zataria multiflora Boiss extract on in vitro and in vivo Th1/Th2 cytokine (IFN-γ/IL4) balance

2013 ◽  
Vol 150 (3) ◽  
pp. 1024-1031 ◽  
Author(s):  
Mohammad Hossein Boskabady ◽  
Sakine Shahmohammadi Mehrjardi ◽  
Abadorrahim Rezaee ◽  
Houshang Rafatpanah ◽  
Sediqeh Jalali
Keyword(s):  
Zataria Multiflora ◽  
Th2 Cytokine ◽  
Ifn Γ ◽  
The Impact

scholarly journals Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 868
Author(s):  
Fabiana Albani Zambuzi ◽  
Priscilla Mariane Cardoso-Silva ◽  
Ricardo Cardoso Castro ◽  
Caroline Fontanari ◽  
Flavio da Silva Emery ◽  
...  
Keyword(s):  
Immune Response ◽  
Hematological Malignancies ◽  
M2 Macrophage ◽  
M2 Polarization ◽  
Tnf Α ◽  
Monocytes And Macrophages ◽  
Ifn Γ ◽  
And Function ◽  
The Impact

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to Mycobacterium tuberculosis in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.

scholarly journals Oxidative Stress Compromises Lymphocyte Function in Neonatal Dairy Calves

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 255
Author(s):  
Wilmer Cuervo ◽  
Lorraine M. Sordillo ◽  
Angel Abuelo
Keyword(s):  
Oxidative Stress ◽  
Immune Responses ◽  
Immune Cell ◽  
Lymphocyte Activation ◽  
Dairy Calves ◽  
Lymphocyte Function ◽  
Newborn Calves ◽  
Ifn Γ ◽  
The Impact

Dairy calves are unable to mount an effective immune response during their first weeks of life, which contributes to increased disease susceptibility during this period. Oxidative stress (OS) diminishes the immune cell capabilities of humans and adult cows, and dairy calves also experience OS during their first month of life. However, the impact that OS may have on neonatal calf immunity remains unexplored. Thus, we aimed to evaluate the impact of OS on newborn calf lymphocyte functions. For this, we conducted two experiments. First, we assessed the association of OS status throughout the first month of age and the circulating concentrations of the cytokines interferon-gamma (IFN-γ) and interleukin (IL) 4, as well as the expression of cytokine-encoding genes IFNG, IL2, IL4, and IL10 in peripheral mononuclear blood cells (PBMCs) of 12 calves. Subsequently, we isolated PBMCs from another 6 neonatal calves to investigate in vitro the effect of OS on immune responses in terms of activation of lymphocytes, cytokine expression, and antibody production following stimulation with phorbol 12-myristate 13-acetate or bovine herpesvirus-1. The results were compared statistically through mixed models. Calves exposed to high OS status in their first month of age showed higher concentrations of IL-4 and expression of IL4 and IL10 and lower concentrations of IFN-γ and expression of IFNG and IL2 than calves exposed to lower OS. In vitro, OS reduced lymphocyte activation, production of antibodies, and protein and gene expression of key cytokines. Collectively, our results demonstrate that OS can compromise some immune responses of newborn calves. Hence, further studies are needed to explore the mechanisms of how OS affects the different lymphocyte subsets and the potential of ameliorating OS in newborn calves as a strategy to augment the functional capacity of calf immune cells, as well as enhance calves’ resistance to infections.

The impact of mental models on the treatment and research of chronic infections due to biofilms

Apmis ◽  
2021 ◽  
Author(s):  
Thomas Bjarnsholt ◽  
Enrico Mastroianni ◽  
Klaus Kirketerp‐Møller ◽  
Philip S. Stewart ◽  
Aline Meret Mähr ◽  
...  
Keyword(s):  
Mental Models ◽  
Chronic Infections ◽  
The Impact
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