scholarly journals Cobalt exposure via skin alters lung immune cells and enhances pulmonary responses to cobalt in mice

2020 ◽  
Vol 319 (4) ◽  
pp. L641-L651 ◽  
Author(s):  
Hung-Chang Tsui ◽  
Tatjana Decaesteker ◽  
Anne-Charlotte Jonckheere ◽  
Greetje Vande Velde ◽  
Jonathan Cremer ◽  
...  

Cobalt has been associated with allergic contact dermatitis and occupational asthma. However, the link between skin exposure and lung responses to cobalt is currently unknown. We investigated the effect of prior dermal sensitization to cobalt on pulmonary physiological and immunological responses after subsequent challenge with cobalt via the airways. BALB/c mice received epicutaneous applications (25 μL/ear) with 5% CoCl2*6H2O (Co) or the vehicle (Veh) dimethyl sulfoxide (DMSO) twice; they then received oropharyngeal challenges with 0.05% CoCl2*6H2O or saline five times, thereby obtaining four groups: Veh/Veh, Co/Veh, Veh/Co, and Co/Co. To detect early respiratory responses noninvasively, we performed sequential in vivo microcomputed tomography (µCT). One day after the last challenge, we assessed airway hyperreactivity (AHR) to methacholine, inflammation in bronchoalveolar lavage (BAL), innate lymphoid cells (ILCs) and dendritic cells (DCs) in the lungs, and serum IgE. Compared with the Veh/Veh group, the Co/Co group showed increased µCT-derived lung response, increased AHR to methacholine, mixed neutrophilic and eosinophilic inflammation, elevated monocyte chemoattractant protein-1 (MCP-1), and elevated keratinocyte chemoattractant (KC) in BAL. Flow cytometry in the Co/Co group demonstrated increased DC, type 1 and type 2 conventional DC (cDC1/cDC2), monocyte-derived DC, increased ILC group 2, and natural cytotoxicity receptor-ILC group 3. The Veh/Co group showed only increased AHR to methacholine and elevated MCP-1 in BAL, whereas the Co/Veh group showed increased cDC1 and ILC2 in lung. We conclude that dermal sensitization to cobalt may increase the susceptibility of the lungs to inhaling cobalt. Mechanistically, this enhanced susceptibility involves changes in pulmonary DCs and ILCs.

VASA ◽  
2020 ◽  
Vol 49 (4) ◽  
pp. 281-284
Author(s):  
Atıf Yolgosteren ◽  
Gencehan Kumtepe ◽  
Melda Payaslioglu ◽  
Cuneyt Ozakin

Summary. Background: Prosthetic vascular graft infection (PVGI) is a complication with high mortality. Cyanoacrylate (CA) is an adhesive which has been used in a number of surgical procedures. In this in-vivo study, we aimed to evaluate the relationship between PVGI and CA. Materials and methods: Thirty-two rats were equally divided into four groups. Pouch was formed on back of rats until deep fascia. In group 1, vascular graft with polyethyleneterephthalate (PET) was placed into pouch. In group 2, MRSA strain with a density of 1 ml 0.5 MacFarland was injected into pouch. In group 3, 1 cm 2 vascular graft with PET piece was placed into pouch and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. In group 4, 1 cm 2 vascular graft with PET piece impregnated with N-butyl cyanoacrylate-based adhesive was placed and MRSA strain with a density of 1 ml 0.5 MacFarland was injected. All rats were scarified in 96th hour, culture samples were taken where intervention was performed and were evaluated microbiologically. Bacteria reproducing in each group were numerically evaluated based on colony-forming unit (CFU/ml) and compared by taking their average. Results: MRSA reproduction of 0 CFU/ml in group 1, of 1410 CFU/ml in group 2, of 180 200 CFU/ml in group 3 and of 625 300 CFU/ml in group 4 was present. A statistically significant difference was present between group 1 and group 4 (p < 0.01), between group 2 and group 4 (p < 0.01), between group 3 and group 4 (p < 0.05). In terms of reproduction, no statistically significant difference was found in group 1, group 2, group 3 in themselves. Conclusions: We observed that the rate of infection increased in the cyanoacyrylate group where cyanoacrylate was used. We think that surgeon should be more careful in using CA in vascular surgery.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Natasha Kishore Pahuja ◽  
Rohit Shetty ◽  
Rudy M. M. A. Nuijts ◽  
Aarti Agrawal ◽  
Arkasubhra Ghosh ◽  
...  

Purpose.To study the corneal nerve morphology and its importance in unilateral keratoconus.Materials and Methods.In this prospective cross-sectional study, 33 eyes of 33 patients with keratoconus in one eye (Group 3) were compared with the other normal eye of the same patients (Group 2) and 30 eyes of healthy patients (Group 1). All patients underwent detailed ophthalmic examination followed by topography with Pentacam HR and in vivo confocal microscopy (IVCM). Five images obtained with IVCM were analyzed using an automated CCmetrics software version 1.0 for changes in subbasal plexus of nerves.Results.Intergroup comparison showed statistically significant reduction in corneal nerve fiber density (CNFD) and length (CNFL) in Group 3 as compared to Group 1 (p<0.001andp=0.001, resp.) and Group 2 (p=0.01andp=0.02, resp.). Though corneal nerve fiber length, diameter, area, width, corneal nerve branch density, and corneal total branch density were found to be higher in decentered cones, only the corneal nerve branch density (CNBD) was found to be statistically significant (p<0.01) as compared to centered cones.Conclusion.Quantitative changes in the corneal nerve morphology can be used as an imaging marker for the early diagnosis of keratoconus before the onset of refractive or topography changes.


2018 ◽  
Vol 115 (52) ◽  
pp. E12313-E12322 ◽  
Author(s):  
Tingting Zheng ◽  
Baohua Zhang ◽  
Ce Chen ◽  
Jingyu Ma ◽  
Deyun Meng ◽  
...  

Dendritic cells (DCs) play pivotal roles in maintaining intestinal homeostasis, but how the DCs regulate diverse immune networks on homeostasis breakdown remains largely unknown. Here, we report that, in response to epithelial barrier disruption, colonic DCs regulate the differentiation of type 1 regulatory T (Tr1) cells through p38α-dependent IL-27 production to initiate an effective immune response. Deletion of p38α in DCs, but not in T cells, led to increased Tr1 and protected mice from dextran sodium sulfate-induced acute colitis and chronic colitis-associated colorectal cancer. We show that higher levels of IL-27 in p38α-deficient colonic cDC1s, but not cDC2s, were responsible for the increase of Tr1 cells. Moreover, p38α-dependent IL-27 enhanced IL-22 secretion from intestinal group 3 innate lymphoid cells and protected epithelial barrier function. In p38α-deficient DCs, the TAK1–MKK4/7–JNK–c-Jun axis was hyperactivated, leading to high IL-27 levels, and inhibition of the JNK–c-Jun axis suppressed IL-27 expression. ChIP assay revealed direct binding of c-Jun to the promoter of Il27p28, which was further enhanced in p38α-deficient DCs. In summary, here we identify a key role for p38α signaling in DCs in regulating intestinal inflammatory response and tumorigenesis, and our finding may provide targets for the treatment of inflammatory intestinal diseases.


Author(s):  
Peyman Sadeghi ◽  
Yagoob Garedaghi ◽  
Mirhadi Khayatnouri ◽  
Hosein Hashemzade Farhang ◽  
Ramin Kaffash Elahi

Introduction: Hydatidosis is a global disease and one of the most dangerous zoonotic diseases which is found in areas where humans, dogs, and herbivores are in close contact with each other. Methods: In this study, a total of 64 rats were divided into control and case groups, and then 3000 protoscolices were injected into the peritoneal cavity. After 2 months, rats in the case group were given triclabendazole + levamisole at a dose of 6 mg + 4.41 mg/mL orally for 60 days, respectively. Then, after 6 months of infection, the rats of the control and case groups were killed by anesthesia and then an autopsy was performed and the viscera were carefully examined for hydatid cyst infection. Results: The results showed that in the control group, 3 cysts were observed in the liver, 10 in the kidney, and 88 in the lung. The mean number of hydatid cysts in this group was determined to be 33.6. In the case group, 2 cysts were observed in the liver, 6 in the kidney, and 64 in the lungs. The mean number of hydatid cysts in the viscera was 24 in the case group. Conclusions: Statistical analysis of the results obtained from the case and control groups showed that the therapeutic efficacy of triclabendazole + levamisole was 31%, which is not enough to treat cases of hydatid cyst.


2018 ◽  
Author(s):  
Maria Pokrovskii ◽  
Jason A. Hall ◽  
David E. Ochayon ◽  
Ren Yi ◽  
Natalia S. Chaimowitz ◽  
...  

SummaryInnate lymphoid cells (ILCs) can be subdivided into several distinct cytokine-secreting lineages that promote tissue homeostasis and immune defense but also contribute to inflammatory diseases. Accumulating evidence suggests that ILCs, similarly to other immune populations, are capable of phenotypic and functional plasticity in response to infectious or environmental stimuli. Yet the transcriptional circuits that control ILC identity and function are largely unknown. Here we integrate gene expression and chromatin accessibility data to infer transcriptional regulatory networks within intestinal type 1, 2, and 3 ILCs. We predict the “core” sets of transcription-factor (TF) regulators driving each ILC subset identity, among which only a few TFs were previously known. To assist in the interpretation of these networks, TFs were organized into cooperative clusters, or modules that control gene programs with distinct functions. The ILC network reveals extensive alternative-lineage-gene repression, whose regulation may explain reported plasticity between ILC subsets. We validate new roles for c-MAF and BCL6 as regulators affecting the type 1 and type 3 ILC lineages. Manipulation of TF pathways identified here might provide a novel means to selectively regulate ILC effector functions to alleviate inflammatory disease or enhance host tolerance to pathogenic microbes or noxious stimuli. Our results will enable further exploration of ILC biology, while our network approach will be broadly applicable to identifying key cell state regulators in otherin vivocell populations.


2009 ◽  
Vol 296 (4) ◽  
pp. L657-L665 ◽  
Author(s):  
Mohammad Abolhassani ◽  
Adeline Guais ◽  
Philippe Chaumet-Riffaud ◽  
Annie J. Sasco ◽  
Laurent Schwartz

The aim of this study was to assess whether one of the most common poisons of cellular respiration, i.e., carbon dioxide, is proinflammatory. CO2 is naturally present in the atmosphere at the level of 0.038% and involved in numerous cellular biochemical reactions. We analyzed in vitro the inflammation response induced by exposure to CO2 for 48 h (0–20% with a constant O2 concentration of 21%). In vivo mice were submitted to increasing concentrations of CO2 (0, 5, 10, and 15% with a constant O2 concentration of 21%) for 1 h. The exposure to concentrations above 5% of CO2 resulted in the increased transcription (RNase protection assay) and secretion (ELISA) of proinflammatory cytokines [macrophage inflammatory protein-1α (MIP-1α), MIP-1β, MIP-2, IL-8, IL-6, monocyte chemoattractant protein-1, and regulated upon activation, normal T cell expressed, and, presumably, secreted (RANTES)] by epithelial cell lines HT-29 or A549 and primary pulmonary cells retrieved from the exposed mice. Lung inflammation was also demonstrated in vivo by mucin 5AC-enhanced production and airway hyperreactivity induction. This response was mostly mediated by the nuclear translocation of p65 NF-κB, itself a consequence of protein phosphatase 2A (PP2A) activation. Short inhibiting RNAs (siRNAs) targeted toward PP2Ac reversed the effect of carbon dioxide, i.e., disrupted the NF-κB activation and the proinflammatory cytokine secretion. In conclusion, this study strongly suggests that exposure to carbon dioxide may be more toxic than previously thought. This may be relevant for carcinogenic effects of combustion products.


Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1872
Author(s):  
Martha Sahylí Ortega Pijeira ◽  
Paulo Sérgio Gonçalves Nunes ◽  
Sofia Nascimento dos Santos ◽  
Zhengxing Zhang ◽  
Arian Pérez Nario ◽  
...  

Losartan is widely used in clinics to treat cardiovascular related diseases by selectively blocking the angiotensin II type 1 receptors (AT1Rs), which regulate the renin-angiotensin system (RAS). Therefore, monitoring the physiological and pathological biodistribution of AT1R using positron emission tomography (PET) might be a valuable tool to assess the functionality of RAS. Herein, we describe the synthesis and characterization of two novel losartan derivatives PET tracers, [18F]fluoroethyl-losartan ([18F]FEtLos) and [18F]ammoniomethyltrifluoroborate-losartan ([18F]AMBF3Los). [18F]FEtLos was radiolabeled by 18F-fluoroalkylation of losartan potassium using the prosthetic group 2-[18F]fluoroethyl tosylate; whereas [18F]AMBF3Los was prepared following an one-step 18F-19F isotopic exchange reaction, in an overall yield of 2.7 ± 0.9% and 11 ± 4%, respectively, with high radiochemical purity (>95%). Binding competition assays in AT1R-expressing membranes showed that AMBF3Los presented an almost equivalent binding affinity (Ki 7.9 nM) as the cold reference Losartan (Ki 1.5 nM), unlike FEtLos (Ki 2000 nM). In vitro and in vivo assays showed that [18F]AMBF3Los displayed a good binding affinity for AT1R-overexpressing CHO cells and was able to specifically bind to renal AT1R. Hence, our data demonstrate [18F]AMBF3Los as a new tool for PET imaging of AT1R with possible applications for the diagnosis of cardiovascular, inflammatory and cancer diseases.


1987 ◽  
Author(s):  
C J Parker ◽  
D E Huber ◽  
A R Hedges ◽  
V V Kakkar

In a randomized clinical trial of 100 patients, the in vivo antithrombotic effects of a subcutaneously administered LMW heparin fraction (CY216) used in the treatment of established DVT, was compared with UF heparin administered by either intravenous or subcutaneous routes.Venograms were used to make the initial diagnosis, and efficacy of treatment was assessed by a repeat venogram done on day 6. Comparison of the venograms were done blind by an expert radiologist.Patients were randomized to one of three groups: Group 1 received subcutaneous CY216; Group 2 received subcutaneous UF heparin: Group 3 received continuous intravenous UF heparin. Random patients from each group had detailed haematological tests consisting of twicedaily KCCT and anti-Xa levels. Extension of thrombus occurred in significantly morepatients receiving intravenous heparin than subcutaneous heparin (p-0.02).There was no difference between the two subcutaneousgroups. There were no haematological complications.We conclude that subcutaneous administratiyon of heparin is the treatment of choice in the treatment of DVT.


1988 ◽  
Vol 254 (4) ◽  
pp. F477-F483 ◽  
Author(s):  
A. van de Stolpe ◽  
R. L. Jamison

Micropuncture collections were obtained from the terminal collecting duct (CD) at base and tip of the renal papilla of the rat. Group 1 was studied before and during infusion with atrial natriuretic peptide (ANP), group 2 was administered the vehicle only, and group 3 received acetazolamide to increase sodium delivery to the base to a similar extent as after ANP. ANP caused a decrease in blood pressure, a slight increase in GFR, natriuresis, and diuresis. Sodium delivery to the collecting duct at the base of the papilla increased. Between base and tip, sodium reabsorption was inhibited. Tubule fluid sodium concentration (TFNa) was increased at the base and remained high at the tip; in contrast TFNa fell between base and tip in control and acetazolamide groups. After acetazolamide, sodium reabsorption in the terminal CD was not inhibited. These results demonstrate that in vivo ANP 1) increases the delivery of sodium to the terminal CD and 2) inhibits sodium reabsorption in the terminal CD. The findings for chloride were similar to those for sodium. ANP also increased delivery of H2O, K, Ca, and Mg to the CD at the papillary base but did not significantly affect their transport by the terminal CD.


2019 ◽  
Vol 89 (6) ◽  
pp. 883-888
Author(s):  
Sérgio Elias Neves Cury ◽  
Silvio Augusto Bellini-Pereira ◽  
Aron Aliaga-Del Castillo ◽  
Sérgio Schneider ◽  
Arnaldo Pinzan ◽  
...  

ABSTRACT Objective: To evaluate the effect of two different prophylaxis protocols on the friction force in sliding mechanics during in vivo leveling and alignment. Materials and Methods: The sample comprised 48 hemi-arches divided into three groups according to the prophylactic protocol adopted. Group 1 consisted of patients undergoing prophylaxis with sodium bicarbonate, group 2 consisted of patients submitted to prophylaxis with glycine, and group 3 consisted of patients without prophylaxis, as a control. All patients received hygiene instructions and, with the exception of group 3, prophylaxis was performed monthly. After 10 months, the brackets were removed from the oral cavity and submitted to friction force tests and qualitative analysis by scanning electron microscopy. Analysis of variance followed by Tukey tests was performed for intergroup comparison regarding the friction force. Results: The experimental groups presented significantly smaller friction forces than the group without prophylaxis. Accordingly, qualitative analysis showed greater debris accumulation in the group without the prophylactic procedures. Conclusions: Prophylactic blasting with sodium bicarbonate or glycine can significantly prevent an increase of the friction force during sliding mechanics.


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