scholarly journals Pulmonary instillation of MWCNT increases lung permeability, decreases gp130 expression in the lungs, and initiates cardiovascular IL-6 transsignaling

2016 ◽  
Vol 310 (2) ◽  
pp. L142-L154 ◽  
Author(s):  
Leslie C. Thompson ◽  
Nathan A. Holland ◽  
Ryan J. Snyder ◽  
Bin Luo ◽  
Daniel P. Becak ◽  
...  
Keyword(s):  
Vascular Tissue ◽  
Epithelial Barrier ◽  
Aortic Tissue ◽  
Serum Concentrations ◽  
Lung Water ◽  
Cell Counts ◽  
Pulmonary Instillation ◽  
The Impact ◽  
Soluble Gp130

Pulmonary instillation of multiwalled carbon nanotubes (MWCNT) has the potential to promote cardiovascular derangements, but the mechanisms responsible are currently unclear. We hypothesized that exposure to MWCNT would result in increased epithelial barrier permeability by 24 h postexposure and initiate a signaling process involving IL-6/gp130 transsignaling in peripheral vascular tissue. To test this hypothesis we assessed the impact of 1 and 10 μg/cm2MWCNT on transepithelial electrical resistance (TEER) and expression of barrier proteins and cell activation in vitro using normal human bronchial epithelial primary cells. Parallel studies using male Sprague-Dawley rats instilled with 100 μg MWCNT measured bronchoalveolar lavage (BAL) differential cell counts, BAL fluid total protein, and lung water-to-tissue weight ratios 24 h postexposure and quantified serum concentrations of IL-6, soluble IL-6r, and soluble gp130. Aortic sections were examined immunohistochemically for gp130 expression, and gp130 mRNA/protein expression was evaluated in rat lung, heart, and aortic tissue homogenates. Our in vitro findings indicate that 10 μg/cm2MWCNT decreased the development of TEER and zonula occludens-1 expression relative to the vehicle. In rats MWCNT instillation increased BAL protein, lung water, and induced pulmonary eosinophilia. Serum concentrations of soluble gp130 decreased, aortic endothelial expression of gp130 increased, and expression of gp130 in the lung was downregulated in the MWCNT-exposed group. We propose that pulmonary exposure to MWCNT can manifest as a reduced epithelial barrier and activator of vascular gp130-associated transsignaling that may promote susceptibility to cardiovascular derangements.

scholarly journals Translational studies of electrophoretic mobility and phase picture of erythrocytes with consideration of development of stress response during a pathological process

2018 ◽  
Vol 46 (8) ◽  
pp. 765-771
Author(s):  
A. V. Deryugina ◽  
M. N. Ivashchenko ◽  
P. S. Ignat'ev ◽  
A. G. Samodelkin
Keyword(s):  
Stress Response ◽  
Electrophoretic Mobility ◽  
Pathological Process ◽  
Diagnostic Methods ◽  
Interference Microscopy ◽  
Control Group ◽  
Cell Counts ◽  
Leukocyte Counts ◽  
The Impact

Rationale:Modern cell diagnostic methods are in high demand during the development of new approaches in personalized medicine. Coherent phase interferometry and cell microelectrophoresis are among such methods that are being actively introduced into the diagnostic process in medical institutions.Aim:To substantiate the potential use of biophysical and morphodensitometrical erythrocytes parameters as criteria of treatment efcacy and course of adaptation process in patients with gastrointestinal tract disorders.Materials and methods:The study included 25 patients aged from 40 to 54 years (11 males and 14 females), among them 9 (36%) with gastric peptic ulcer, 3 (12%) with duodenal ulcer, 8 (32%) with acute gastritis, and 5 (20%) with acute pancreatitis. Biophysical and morphological particulars of peripheral blood erythrocytes were assessed before and after treatment using cell diagnostic techniques, such as microelectrophoresis and laser modulation interference microscopy. Also, we evaluated changes over time in routine clinical laboratory tests, such as red and white blood cell counts, hemoglobin levels, and erythrocyte sedimentation rate (ESR), and differential leukocyte counts. The control group included 10 healthy donors aged from 36 to 52 years.In vitroexperiments were performed to assess the erythrocyte electrophoretic mobility (EEPM) and morphology of erythrocytes treated with epinephrine or cortisol.Results:After the treatment, the patients demonstrated a decrease in their leukocyte counts (by 27%), a 2-fold increase in monocyte counts and an ESR decrease (by 10%), compared to the corresponding baseline values before treatment (p < 0.05 for all comparisons). EEPM increased by 12% (1.37 vs. 1.22 mcm × cm/V × s, p < 0.05). The erythrocyte pool of the patients before treatment, had a decreased proportion of discocytes, compared to that in the control group (85.2 vs. 95.4%, р < 0.05), increased proportions of echinocytes, stomatocytes and degenerative forms (11, 2.8 and 1%, respectively, р < 0.05). After the treatment, the discocytes counts increased virtually up to their physiological normal range (91.3%). However, the surface of the discoid cells remained heterogeneous with multiple microspicules; this resulted in changes of electrokinetic and morphological properties of erythrocyte response to stress reaction occurring in the body. The impact of the stress effectors was confrmed inin vitroexperiments assessing the effects of epinephrine (1 × 10-9 g/mL) and cortisol (5 × 10-7 g/mL) on erythrocytes. At 120 minutes of the experiment, epinephrine decreased EEPM (1.14 vs. 1.24 mcm × cm/V × s at baseline, р < 0.05) and increased cell sphericity. On the contrary, cortisol increased EEPM (1.72 vs. 1.36 mcm × cm/V × s, р < 0.05), with non-signifcant echinocytic transformation.Conclusion:Biophysical and morphodensitometric parameters of red blood cells obtained with the use of current express methods of cell microelectrophoresis and coherent interference microscopy help to objectivize the intensity of stress response during a pathological process and activation of adaptation mechanisms during the treatment.

scholarly journals The effect of a professional cricket match schedule on selected immune parameters

2004 ◽  
Vol 16 (2) ◽  
pp. 22
Author(s):  
AW Williams ◽  
KH Myburgh ◽  
C Smith
Keyword(s):  
Sports Medicine ◽  
Lymphocyte Activation ◽  
Lymphocyte Subpopulation ◽  
Upper Respiratory Tract ◽  
Cd4 Cells ◽  
Immune Parameters ◽  
Cell Counts ◽  
Cd69 Expression ◽  
The Impact

Objective. The impact of a professional cricket match schedule on white blood cell (WBC) distribution and lymphocyte activation (CD69 expression) was investigated. Methods. After a 3-month pre-season training period, physical and immune parameters were determined in 14 male cricketers before (B) and after (A) an intensive 5- week match schedule. Results. Exercise test results were unchanged from B to A. Total WBC counts were similar, but total lymphocyte and lymphocyte subpopulation counts decreased significantly. The CD4:CD8 ratio did not change. After in vitro stimulation, percentage CD4+CD69+ cells increased (B: 54.4 ± 9.7%, A: 64.0 ± 8.5%, p < 0.01), but absolute CD4+CD69+ cell counts did not change from B to A. In contrast, both the %CD8+CD69+ cells and absolute CD8+CD69+ cell count remained similar. Conclusion. A strenuous, interregional, professional cricket match schedule resulted in a decreased number of lymphocytes, but relatively increased in vitro reactivity of CD4+ cells, thus maintaining the absolute capacity of the CD4+ cells to become activated on stimulation. In cricketers who suffered upper respiratory tract symptoms during the match schedule (N = 7), none of the immune parameters investigated differed significantly from the others at B or A. SA Sports Medicine Vol.16(2) 2004: 22-27

Loss of Id4 Accelerates CLL Progression in TCL1 Mice

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3153-3153
Author(s):  
Shih-Shih Chen ◽  
Amy J. Johnson ◽  
Rainer Claus ◽  
Fred Sablitzky ◽  
Christoph Plass ◽  
...  
Keyword(s):  
B Cells ◽  
Dna Binding ◽  
Disease Progression ◽  
Dominant Negative ◽  
P Value ◽  
Bhlh Transcription Factor ◽  
Lymphoid Tissues ◽  
Cell Counts ◽  
The Impact

Abstract The inhibitor of DNA binding protein 4 (ID4) is a member of dominant negative basic helix loop helix (bHLH) transcription factor family that has a HLH domain but lacking DNA-binding domain. Methylation of ID4 in B-cell lineage malignancies including CLL and germinal center non-Hodgkin lymphomas (GC-NHLs) has been described. To date, the impact of Id4 loss in CLL has not been demonstrated. We utilized the TCL1 transgenic mouse model of human CLL to study the importance of loss of ID4 in disease progression. We demonstrated that ID4 was silenced by methylation only at the time mice had symptomatic leukemia. We therefore sought to investigate if earlier loss of Id4 would accelerate CLL progression. We generated mice with haploid loss of Id4 in TCL1 transgenic background by breeding homozygous TCL1 transgenic mice and mice with heterozygous Id4 mutant gene. By comparing to the control littermates with heterozygous TCL1 oncogene, mice with the loss of Id4 occur to have significantly accelerated CLL disease progression with shorter overall survival (12 versus 16 months, p-value&lt;0.0001). The pathological analysis on Id4 mutant mice demonstrated that the CLL symptoms such as the elevated white blood cell counts, enlarged spleen and lymphoid tissues. We then performed the microarray studies on 1 month old TCL1 mice with control or mutant Id4 to identify ID4-dependent transcriptional changes in primary B-cells. Among the identified targets, genes involved in cell proliferation and anti-apoptosis were then verified. Supportively, B-cells from Id4 mutant TCL1 mice have significantly (p-value&lt;0.001) diminished apoptosis in response to dexamethasone treatment. Additionally, both significant in vitro (p-value&lt;0.001) and in vivo (p-value=0.025) increased proliferation of Id4 mutant TCL1 B-cells after the stimulation by CpG685NO168 was demonstrated. These data provide support that Id4 acts as tumor suppressor in transformed B-lymphocytes and is silenced through the process of methylation. The Effort to identify binding partners of Id4 in CLL cells and targeting its re-expression is warranted.

Implementation of Vancomycin Monitoring Criteria in a Pediatric Hospital

2004 ◽  
Vol 9 (3) ◽  
pp. 179-186
Author(s):  
Kelley R. Lee ◽  
Stephanie J. Phelps
Keyword(s):  
Blood Cell ◽  
Serum Creatinine ◽  
White Blood Cell ◽  
Primary Objective ◽  
Serum Concentrations ◽  
Cell Counts ◽  
Group 2 ◽  
Serum Vancomycin ◽  
Group 1

OBJECTIVES The primary objective of this retrospective study was to determine if implementation of vancomycin monitoring criteria could reduce the number of serum vancomycin concentrations obtained without adversely affecting patient outcomes. BACKGROUND Controversy regarding the correlation between serum vancomycin concentrations and its efficacy and/or toxicity persists. Little evidence has shown a correlation between vancomycin peak concentration (20–40 mg/L) and toxicity. Likewise, there is little information that supports an association between trough (5–15 mg/L) serum concentrations and clinical cure or in vitro killing rates. For these reasons, many question the clinical utility and cost-effectiveness of monitoring serum vancomycin concentrations. METHODS We reviewed medical records of 193 patients (1 d-19 yrs) who received vancomycin during a 2-month period before (Group 1; n = 100) and after (Group 2; n = 93) implementation of vancomycin monitoring criteria. RESULTS There was no difference (P &gt; 0.05) in baseline age, weight, white blood cell count, temperature, serum creatinine, and blood urea nitrogen between Groups 1 and 2. Although 49.5% of all patients had vancomycin serum concentrations performed, significantly (P &lt; 0.005) fewer patients in Group 2 (32%) were monitored when compared to Group 1 (65%). Peak serum vancomycin concentrations were within the reference range (20–40 mg/L) in 48% of patients in Group 1 compared to 80% in Group 2 (P = 0.03). The mean duration of vancomycin therapy was greater (P = 0.004) for patients in Group 1 (7 ± 7.5 days) compared to Group 2 (4 ± 4.4 days) and the medians for the two groups were also different. Mean ending temperatures (P = 0.23), white blood cell counts (P = 0.71), serum creatinine (P = 0.3) and BUN (P = 0.24) were not different for the two groups. CONCLUSIONS Implementation of criteria to decrease unnecessary serum vancomycin concentration monitoring does not adversely affect patient outcome and may decrease cost to the institution, healthcare system, and patient.

Alveolar macrophage depletion is associated with increased surfactant pool sizes in adult rats

2007 ◽  
Vol 103 (2) ◽  
pp. 637-645 ◽  
Author(s):  
Amy Forbes ◽  
Mike Pickell ◽  
Mehry Foroughian ◽  
Li-Juan Yao ◽  
James Lewis ◽  
...  
Keyword(s):  
Protein A ◽  
Surfactant Protein ◽  
Normal Lung ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Cell Counts ◽  
And Function ◽  
The Impact ◽  
Pool Sizes

Pulmonary surfactant is a lipid-protein material that is essential for normal lung function. Maintaining normal and consistent alveolar amounts of surfactant is in part dependent on clearance of surfactant by alveolar macrophages (AM). The present study utilized a rat model of AM depletion to determine the impact on surfactant pool sizes and function over time. Male Sprague-Dawley rats were anesthetized and intratracheally instilled with PBS-liposomes (PBS-L) or dichloromethylene diphosphonic acid (DMDP) containing liposomes (DMDP-L) and were killed at various time points up to 21 days for compliance measurements, AM cell counts, and surfactant analysis. AM numbers were significantly decreased 1, 2, and 3 days after instillation in DMDP-L vs. PBS-L, with 72% depletion at 3 days. AM numbers returned to normal levels by 5 days. In DMDP-L rats, there was a rapid increase in surfactant-phospholipid pools, showing a ninefold increase in the amount of surfactant in the lavage 3 days after liposome instillation. Surfactant accumulation progressed up to 7 days, with pools normalizing by 21 days. The increase in surfactant was due to increases in both subfractions of surfactant, the large aggregates (LA) and small aggregates. Surfactant protein A levels, relative to LA phospholipids, were not increased. There was a decreased extent of surfactant conversion in vitro for LA from DMDP-L rats compared with controls. It is concluded that the procedure of AM depletion significantly affects surfactant metabolism. The increased endogenous surfactant must be considered when utilizing the AM depletion model to study the role of these cells during lung insults.

scholarly journals Cornelian Cherry Iridoid-Polyphenolic Extract Improves Mucosal Epithelial Barrier Integrity in Rat Experimental Colitis and Exerts Antimicrobial and Antiadhesive Activities In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Marta Szandruk-Bender ◽  
Maria Rutkowska ◽  
Anna Merwid-Ląd ◽  
Benita Wiatrak ◽  
Adam Szeląg ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Epithelial Barrier ◽  
Trinitrobenzenesulfonic Acid ◽  
Cornelian Cherry ◽  
Polyphenolic Extract ◽  
Tnf Α ◽  
The Impact

Background and Aims. Inflammatory bowel disease pharmacotherapy, despite substantial progress, is still not satisfactory for both patients and clinicians. In view of the chronic and relapsing disease course and not always effective treatment with adverse effects, attempts to search for new, more efficient, and safer substances are essential and reasonable. This study was designed to elucidate the impact of cornelian cherry iridoid-polyphenolic extract (CE) and loganic acid (LA) on adherent-invasive E. coli growth and adhesion in vitro and to assess the effect of pretreatment with CE or LA on the course of intestinal inflammation in rat experimental colitis compared with sulfasalazine. Methods. Antibacterial and antiadhesive activities of CE and LA were assessed using microdilution, Int407 cell adherence, and yeast agglutination assays. The colitis model was induced by 2,4,6-trinitrobenzenesulfonic acid. Studied substances were administered intragastrically for 16 days prior to colitis induction. Body weight loss; colon index; histological injuries; IL-23, IL-17, TNF-α, and chemerin levels; and STAT3, Muc2, and TFF3 mRNA expression were evaluated. Results. Only CE exerted antimicrobial and antiadhesive activities in vitro and alleviated colonic symptoms. CE coadministrated with sulfasalazine was more effective than single compounds in reversing increased concentrations of TNF-α, IL-17, and chemerin and decreased Muc2 mRNA expression. Conclusions. CE exerted a protective effect against experimental colitis via impaired mucosal epithelial barrier restoration and intestinal inflammatory response attenuation and given concomitantly with sulfasalazine counteracted colitis in a more effective way than sulfasalazine alone, which indicates their synergistic interaction. The beneficial effect of CE may also be due to its bacteriostatic and antiadhesive activities.

Stimulation of aortic tissue calcium uptake by an extract of spontaneously hypertensive rats erythrocytes possessing hypertensive properties

1986 ◽  
Vol 64 (12) ◽  
pp. 1515-1520 ◽  
Author(s):  
G. L. Wright ◽  
M. E. Rogerson ◽  
W. D. McCumbee
Keyword(s):  
Spontaneously Hypertensive Rats ◽  
Calcium Uptake ◽  
Vascular Tissue ◽  
Aortic Tissue ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
High K ◽  
Tissue Sensitivity ◽  
Tissue Calcium

In earlier reports we have described the isolation of a fraction from the erythrocytes of spontaneously hypertensive rats that produced hypertension when administered to normotensive rats. In addition, it was found that the fraction stimulated the uptake of "lanthanum-resistant" calcium by aortic rings excised from normotensive rats. In these studies we have found that the fraction causes a greater increase in the in vitro uptake of calcium by aortic tissue than that produced by depolarization of the tissue with high K+ or the receptor-mediated influx of calcium induced with norepinephrine. The hypertensive fraction appeared to be more effective in promoting increased calcium uptake in rabbit than in rat aortic tissue, suggesting that significant differences in tissue sensitivity to the active compound(s) may exist between species. In addition, we obtained evidence indicating that the tissue sensitivity to the action of the hypertensive fraction was greater in aortae from spontaneously hypertensive rats than from those of normotensive animals. Attempts to block the action of the hypertensive fraction with verapamil, nifedipine, and sodium nitroprusside had no significant effect on the elevation in tissue calcium. It was found, however, that the action of the hypertensive fraction was temperature dependent with reduced activity at lower temperatures. The data suggest that a compound(s) is present in the erythrocytes of rats that may have a marked effect on vascular tissue metabolism of calcium.

scholarly journals P681 Higher in vitro mucin degradation, but no increased paracellular permeability by faecal water from Crohn’s disease patients

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S601-S601
Author(s):  
H Becker ◽  
N Kameli ◽  
A Rustichelli ◽  
H Britt ◽  
F Stassen ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Barrier Function ◽  
Disease Onset ◽  
Paracellular Permeability ◽  
Epithelial Barrier ◽  
Rrna Gene ◽  
Relative Abundances ◽  
The Impact

Abstract Background Crohn’s disease (CD) is a chronic inflammatory gastro-intestinal condition with a variable disease course. Impaired intestinal integrity and microbial dysbiosis are associated with disease onset and exacerbations. We hypothesized that a perturbed microbial activity in CD patients may contribute to the impaired barrier function. Therefore, this study aimed to examine the impact of faecal bacterial products of active CD patients, CD patients in remission, and healthy controls (HC) on mucin degradation and intestinal epithelial barrier function in vitro. Methods Six HC and twelve CD patients were included. Faecal samples were obtained within one week prior to endoscopy processed within 6 hours after collection. Disease activity was determined by the short endoscopic score for CD (SES-CD). Faecal water (FW) and bacterial membrane vesicles (MVs) were applied on mucin agar to determine mucin degradation. Further, differentiated Caco-2 cell monolayers were exposed to FW and MVs to assess transepithelial electrical resistance (TEER) and paracellular junction stability using permeation of fluorescein isothiocyanate-labelled dextran of 4 kDa. Relative abundances of faecal bacterial genera were evaluated by 16S rRNA gene amplicon sequencing. Results FW-induced mucin degradation was higher in CD samples as compared to HC (p&lt;0.01), but was not linked to specific bacterial relative abundances. FW resulted in 78–87% decrease of TEER in three of the remissive (p&lt;0.001) but not the active CD or HC samples. The decrease of TEER was not linked to increased paracellular permeability. MVs did not induce mucin degradation or epithelial barrier disruption. Conclusion The higher mucin degradation capacity of CD patient-derived FW might indicate contributions of microbial products to CD pathophysiology and warrants further investigation. Moreover, the altered epithelial resistance in some individuals is not due to paracellular alterations.

Differential impact of rhamnolipids and polysorbate80 on composition and functionality of the gut microbiota in the SHIME system.

2021 ◽  
Author(s):  
Lisa Miclotte ◽  
Ellen De Paepe ◽  
Qiqiong Li ◽  
Andreja Rajkovic ◽  
John Van Camp ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Enrichment Analysis ◽  
Human Colon ◽  
Pathway Enrichment Analysis ◽  
Analysis Tool ◽  
Longitudinal Impact ◽  
Cell Counts ◽  
The Impact

Dietary emulsifiers have been shown to affect the composition and function of the gut microbial community, both in vivo and in vitro. Yet, several knowledge gaps remain to be addressed: the impact from a longer timeframe exposure on the gut microbiota, interindividual variability in microbiome response and the putative impact from novel clean label alternatives for current food emulsifiers. In the present study, the impact of one conventional dietary emulsifier, TWEEN80, and one potential novel alternative, rhamnolipids, on the human gut microbiota was investigated using the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME). The faecal microbiota from two human donors, with high and low responsiveness to the emulsifiers, were exposed to 0,05 m% and 0,5 m% of the emulsifiers for 7 days. The results confirmed previous observations that the effects on the composition and functionality are both emulsifier- and donor dependent. The effects reached an equilibrium after about 3 days of exposure. Overall, TWEEN80 and rhamnolipids displayed opposite effects: TWEEN80 increased cell counts, reduced propionate concentration, increased butyrate levels, increased a.o. Faecalibacterium, Blautia and Hungatella abundance, while rhamnolipids did the opposite. Rhamnolipids also sharply increased the abundance of unclassified Lachnospiraceae. On the other hand, both emulsifiers increased the relative abundance of unclassified Enterobacteriaceae. Both emulsifiers also altered the microbial metabolome in different ways and a pathway enrichment analysis tool revealed that the metabolome alterations could be reminiscent of gut issues and obesity. Overall, the impact from the rhamnolipids was larger than that of TWEEN80 at similar concentrations, indicating that the former may not necessarily be a safer alternative for the latter. The response of the microbiota also depended on its original composition and the sensitivity status for which the faecal donors were selected, was preserved. Whether the same donor-diversity and longitudinal impact can be expected in the human colon as well and what impact this has on the host will have to be further investigated.

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