scholarly journals Macrophages of diverse phenotypes drive vascularization of engineered tissues

2020 ◽  
Vol 6 (18) ◽  
pp. eaay6391 ◽  
Author(s):  
P. L. Graney ◽  
S. Ben-Shaul ◽  
S. Landau ◽  
A. Bajpai ◽  
B. Singh ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Cell Behavior ◽  
Short Term ◽  
M1 Macrophages ◽  
Sprouting Angiogenesis ◽  
Engineered Tissues ◽  
Short Term Exposure ◽  
Vessel Networks

Macrophages are key contributors to vascularization, but the mechanisms behind their actions are not understood. Here, we show that diverse macrophage phenotypes have distinct effects on endothelial cell behavior, with resulting effects on vascularization of engineered tissues. In Transwell coculture, proinflammatory M1 macrophages caused endothelial cells to up-regulate genes associated with sprouting angiogenesis, whereas prohealing (M2a), proremodeling (M2c), and anti-inflammatory (M2f) macrophages promoted up-regulation of genes associated with pericyte cell differentiation. In 3D tissue-engineered human blood vessel networks in vitro, short-term exposure (1 day) to M1 macrophages increased vessel formation, while long-term exposure (3 days) caused regression. When human tissue-engineered blood vessel networks were implanted into athymic mice, macrophages expressing markers of both M1 and M2 phenotypes wrapped around and bridged adjacent vessels and formed vessel-like structures themselves. Last, depletion of host macrophages inhibited remodeling of engineered vessels, infiltration of host vessels, and anastomosis with host vessels.

Short-Term Exposure of Cancer Cells to Micromolar Doses of Paclitaxel, with or without Hyperthermia, Induces Long-Term Inhibition of Cell Proliferation and Cell Death In Vitro

2007 ◽  
Vol 14 (3) ◽  
pp. 1220-1228 ◽  
Author(s):  
John Michalakis ◽  
Spyros D. Georgatos ◽  
Eelco de Bree ◽  
Hara Polioudaki ◽  
John Romanos ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Death ◽  
Cancer Cells ◽  
Short Term ◽  
Short Term Exposure

scholarly journals Thymidine-Dependent Staphylococcus aureus Small-Colony Variants Are Induced by Trimethoprim-Sulfamethoxazole (SXT) and Have Increased Fitness during SXT Challenge

2015 ◽  
Vol 59 (12) ◽  
pp. 7265-7272 ◽  
Author(s):  
Andre Kriegeskorte ◽  
Nicola Ivan Lorè ◽  
Alessandra Bragonzi ◽  
Camilla Riva ◽  
Marco Kelkenberg ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Short Term ◽  
Small Colony Variants ◽  
Content Type ◽  
Short Term Exposure ◽  
Small Colony ◽  
Selection Of

ABSTRACTTrimethoprim-sulfamethoxazole (SXT) is a possible alternative for the treatment of community- and hospital-acquired methicillin-resistantStaphylococcus aureus(MRSA) due to the susceptibility of most MRSA strains to the drug. However, after long-term treatment with SXT, thymidine-dependent (TD) SXT-resistant small-colony variants (SCVs) emerge. In TD-SCVs, mutations of thymidylate synthase ([TS]thyA) occur. Until now, it has never been systematically investigated that SXT is triggering the induction and/or selection of TD-SCVs. In our study, we performed induction, reversion, and competition experimentsin vitroandin vivousing a chronic mouse pneumonia model to determine the impact of SXT on the emergence of TD-SCVs. SCVs were characterized by light and transmission electron microscopy (TEM) and auxotrophism testing. Short-term exposure ofS. aureusto SXT induced the TD-SCV phenotype inS. aureusSH1000, while selection of TD-SCVs withthyAmutations occurred after long-term exposure. In reversion experiments with clinical and laboratory TD-SCVs, all revertants carried compensating mutations at the initially identified mutation site. Competition experimentsin vitroandin vivorevealed a survival and growth advantage of the ΔthyAmutant under low-thymidine availability and SXT exposure although this advantage was less profoundin vivo. Our results show that SXT induces the TD-SCV phenotype after short-term exposure, while long-term exposure selects forthyAmutations, which provide an advantage for TD-SCVs under specified conditions. Thus, our results further an understanding of the dynamic processes occurring during SXT exposure with induction and selection ofS. aureusTD-SCVs.

Ultrastructural investigations of MDL 19,660-induced effects on the canine platelet and megakaryocyte

1990 ◽  
Vol 48 (3) ◽  
pp. 374-375
Author(s):  
D.E. Loudy ◽  
J. Sprinkle-Cavallo ◽  
J.T. Yarrington ◽  
F.Y. Thompson ◽  
J.P. Gibson
Keyword(s):  
Antidepressant Drug ◽  
Beagle Dogs ◽  
Long Term Effects ◽  
Short Term ◽  
Platelet Counts ◽  
Toxicological Studies ◽  
Induced Aggregation ◽  
Internal Architecture

Previous short term toxicological studies of one to two weeks duration have demonstrated that MDL 19,660 (5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3Hl, 2,4-triazole-3-thione), an antidepressant drug, causes a dose-related thrombocytopenia in dogs. Platelet counts started to decline after two days of dosing with 30 mg/kg/day and continued to decrease to their lowest levels by 5-7 days. The loss in platelets was primarily of the small discoid subpopulation. In vitro studies have also indicated that MDL 19,660: does not spontaneously aggregate canine platelets and has moderate antiaggregating properties by inhibiting ADP-induced aggregation. The objectives of the present investigation of MDL 19,660 were to evaluate ultrastructurally long term effects on platelet internal architecture and changes in subpopulations of platelets and megakaryocytes.Nine male and nine female beagle dogs were divided equally into three groups and were administered orally 0, 15, or 30 mg/kg/day of MDL 19,660 for three months. Compared to a control platelet range of 353,000- 452,000/μl, a doserelated thrombocytopenia reached a maximum severity of an average of 135,000/μl for the 15 mg/kg/day dogs after two weeks and 81,000/μl for the 30 mg/kg/day dogs after one week.

The Effect of Dimethyl Sulfoxide on In Vitro Platelet Function

1976 ◽  
Vol 36 (01) ◽  
pp. 221-229 ◽  
Author(s):  
Charles A. Schiffer ◽  
Caroline L. Whitaker ◽  
Morton Schmukler ◽  
Joseph Aisner ◽  
Steven L. Hilbert
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Dimethyl Sulfoxide ◽  
Platelet Function ◽  
Platelet Volume ◽  
Short Term ◽  
Platelet Factor ◽  
Short Term Exposure ◽  
Structural Abnormalities

SummaryAlthough dimethyl sulfoxide (DMSO) has been used extensively as a cryopreservative for platelets there are few studies dealing with the effect of DMSO on platelet function. Using techniques similar to those employed in platelet cryopreservation platelets were incubated with final concentrations of 2-10% DMSO at 25° C. After exposure to 5 and 10% DMSO platelets remained discoid and electron micrographs revealed no structural abnormalities. There was no significant change in platelet count. In terms of injury to platelet membranes, there was no increased availability of platelet factor-3 or leakage of nucleotides, 5 hydroxytryptamine (5HT) or glycosidases with final DMSO concentrations of 2.5, 5 and 10% DMSO. Thrombin stimulated nucleotide and 5HT release was reduced by 10% DMSO. Impairment of thrombin induced glycosidase release was noted at lower DMSO concentrations and was dose related. Similarly, aggregation to ADP was progressively impaired at DMSO concentrations from 1-5% and was dose related. After the platelets exposed to DMSO were washed, however, aggregation and release returned to control values. Platelet aggregation by epinephrine was also inhibited by DMSO and this could not be corrected by washing the platelets. DMSO-plasma solutions are hypertonic but only minimal increases in platelet volume (at 10% DMSO) could be detected. Shrinkage of platelets was seen with hypertonic solutions of sodium chloride or sucrose suggesting that the rapid transmembrane passage of DMSO prevented significant shifts of water. These studies demonstrate that there are minimal irreversible alterations in in vitro platelet function after short-term exposure to DMSO.

Short-term exposure and long-term consequences of neonatal exposure to Δ9-tetrahydrocannabinol (THC) and ibuprofen in mice

2016 ◽  
Vol 307 ◽  
pp. 137-144 ◽  
Author(s):  
Gaëtan Philippot ◽  
Fred Nyberg ◽  
Torsten Gordh ◽  
Anders Fredriksson ◽  
Henrik Viberg
Keyword(s):  
Neonatal Exposure ◽  
Short Term ◽  
Short Term Exposure ◽  
Long Term Consequences

scholarly journals Spatio-temporal associations of air pollutant concentrations, GP respiratory consultations and respiratory inhaler prescriptions: a 5-year study of primary care in the borough of Lambeth, South London

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Mark Ashworth ◽  
◽  
Antonis Analitis ◽  
David Whitney ◽  
Evangelia Samoli ◽  
...  
Keyword(s):  
Primary Care ◽  
Negative Binomial ◽  
Hospital Admissions ◽  
Air Pollutant ◽  
Respiratory Morbidity ◽  
Short Term ◽  
Short Term Exposure ◽  
Short And Long Term ◽  
Spatio Temporal

Abstract Background Although the associations of outdoor air pollution exposure with mortality and hospital admissions are well established, few previous studies have reported on primary care clinical and prescribing data. We assessed the associations of short and long-term pollutant exposures with General Practitioner respiratory consultations and inhaler prescriptions. Methods Daily primary care data, for 2009–2013, were obtained from Lambeth DataNet (LDN), an anonymised dataset containing coded data from all patients (1.2 million) registered at general practices in Lambeth, an inner-city south London borough. Counts of respiratory consultations and inhaler prescriptions by day and Lower Super Output Area (LSOA) of residence were constructed. We developed models for predicting daily PM2.5, PM10, NO2 and O3 per LSOA. We used spatio-temporal mixed effects zero inflated negative binomial models to investigate the simultaneous short- and long-term effects of exposure to pollutants on the number of events. Results The mean concentrations of NO2, PM10, PM2.5 and O3 over the study period were 50.7, 21.2, 15.6, and 49.9 μg/m3 respectively, with all pollutants except NO2 having much larger temporal rather than spatial variability. Following short-term exposure increases to PM10, NO2 and PM2.5 the number of consultations and inhaler prescriptions were found to increase, especially for PM10 exposure in children which was associated with increases in daily respiratory consultations of 3.4% and inhaler prescriptions of 0.8%, per PM10 interquartile range (IQR) increase. Associations further increased after adjustment for weekly average exposures, rising to 6.1 and 1.2%, respectively, for weekly average PM10 exposure. In contrast, a short-term increase in O3 exposure was associated with decreased number of respiratory consultations. No association was found between long-term exposures to PM10, PM2.5 and NO2 and number of respiratory consultations. Long-term exposure to NO2 was associated with an increase (8%) in preventer inhaler prescriptions only. Conclusions We found increases in the daily number of GP respiratory consultations and inhaler prescriptions following short-term increases in exposure to NO2, PM10 and PM2.5. These associations are more pronounced in children and persist for at least a week. The association with long term exposure to NO2 and preventer inhaler prescriptions indicates likely increased chronic respiratory morbidity.

Proliferation and agglutinability of primary and transformed human epithelial cells in culture

1976 ◽  
Vol 21 (3) ◽  
pp. 553-561
Author(s):  
M.A. Ricard ◽  
R.J. Hay
Keyword(s):  
Culture Medium ◽  
Monolayer Culture ◽  
Primary Cultures ◽  
Short Term ◽  
Chloromethyl Ketone ◽  
Normal Populations ◽  
Short Term Exposure ◽  
Cell Strains ◽  
Human Placentae

Primary epithelial populations (HAM) were obtained by dissociation of the amniotic membrane stripped from human placentae. Agglutinability of cells from such normal populations and of cells from the transformed epithelial line WISH was then compared using concavanalin A as mediator. Extensive similar studies have previously been reported with cell strains isolated from other species. Freshly dissociated HAM cells from primary cultures agglutinated much less readily than did cells from WISH populations. Furthermore, the former exhibited a drastic decline in agglutinability as a function of time in suspension culture after trypsinization. Short-term exposure (60 h) of HAM cells in monolayer culture to 5-bromodeoxyuridine (BrdU) elicited heightened agglutinability detectable through 22 days in vitro. Addition of the protease inhibitors n-tosyl-L-lysyl-chloromethyl ketone (TLCK) or p-tosyl-L-arginine-methyl ester (TAME) to the culture medium inhibited proliferation of the WISH line by 40–50% while effecting only a 10–15% inhibition of HAM cells. These results also confirm data with other cell species indicating that high proteolytic activity at the surface of transformed cells may be related to the rapid proliferation rate.

scholarly journals Effects of Long-Term Triclosan Exposure on Microbiota in Zebrafish

2021 ◽  
Vol 12 ◽  
Author(s):  
Ning Tang ◽  
Pianpian Fan ◽  
Xiaogang Yu ◽  
Rui Ma ◽  
Yexuan Tao ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Early Adulthood ◽  
Rrna Gene ◽  
Adult Zebrafish ◽  
Short Term ◽  
Microbial Composition ◽  
Short Term Exposure ◽  
Embryonic Life ◽  
A Minor

Background: Triclosan (TCS) is a widely used antibacterial agent in personal care products and is ubiquitous in the environment. We aimed to examine whether TCS exposure affects microbiota in the gastrointestinal tract of zebrafish.Methods: After exposure to TCS 0 (Dimethyl Sulphoxide, DMSO control), 0.03, 0.3, 3, 30, 100, and 300ng/ml, respectively, from day 0 to 120days post fertilization (dpf), or for 7days in adult 4-month zebrafish, the long- and short-term impact of TCS exposure on the microbiome in the gastrointestinal tract was evaluated by analyzing 16S rRNA gene V3-V4 region sequencing.Results: The top two most dominant microbiota phyla were Proteobacteria and Fusobacteria phylum in all zebrafish groups. In TCS exposure 0–120 dpf, compared with DMSO control, the mean number of microbial operational taxonomic units (OTUs) was 54.46 lower (p<0.0001), Chao indice 41.40 lower (p=0.0004), and Ace indice 34.10 lower (p=0.0044) in TCS 300ng/ml group, but no change was observed in most of the other TCS concentrations. PCoA diagram showed that the microbial community in the long-term TCS 300ng/ml exposure group clustered differently from those in the DMSO control and other TCS exposure groups. A shorter body length of the zebrafish was observed in the long-term TCS exposure at 0.03, 100, and 300ng/ml. For 7-day short-term exposure in adult zebrafish, no difference was observed in alpha or beta diversity of microbiota nor the relative abundance of Proteobacteria or Fusobacteria phylum among DMSO control and any TCS levels, but a minor difference in microbial composition was observed for TCS exposure.Conclusions: Long-term exposure to high TCS concentration in a window from early embryonic life to early adulthood may reduce diversity and alter the composition of microbiota in the gastrointestinal tract. The effect of short-term TCS exposure was not observed on the diversity of microbiota but there was a minor change of microbial composition in adult zebrafish with TCS exposure.

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