Assessment of the Skin Irritancy Potential of Synthetic Detergents (Syndets)

1984 ◽  
Vol 12 (1) ◽  
pp. 25-32
Author(s):  
P.J. Dykes ◽  
D.L. Williams ◽  
L.A. Jenner ◽  
R. Marks
Keyword(s):  
Rank Order ◽  
Viable Cell ◽  
Skin Surface ◽  
Test System ◽  
Human Skin Fibroblasts ◽  
Test Systems ◽  
Viable Cells ◽  
Cell Layers

Summary Among the factors which determine the degree of damage to the skin are (a) the resistance of the stratum corneum to the solubilisation of its components, (b) the intrinsic toxicity of the compound, and (c) the susceptibility of the viable cell layers to damage. In this study of the toxicity of syndets we have attempted to compare their properties in vivo and in vitro and relate these to cutaneous irritancy studies in normal volunteers. The “solubilising” effect of a series of syndets has been studied using the forced desquamation technique. Although no differences could be determined in terms of the corneocytes released from the skin surface, the protein solubilised did differ according to the syndet used and a rank order could be obtained. The susceptibility of viable cells to lysis by syndets has been studied in vitro, using human skin fibroblasts. This test system was able to discriminate between the different syndets and gave the same rank order as the in vivo human test. Comparison with the standard cutaneous irritancy test indicated some correlation between the two test systems and the irritancy test. However, the rank order correlation did show some discrepancy, and the use of such test systems as predictors of cutaneous irritancy is still being investigated.

Role of the ligand in intracellular receptor function: receptor affinity determines activation in vitro of the latent dioxin receptor to a DNA-binding form

1991 ◽  
Vol 11 (1) ◽  
pp. 401-411
Author(s):  
S Cuthill ◽  
A Wilhelmsson ◽  
L Poellinger
Keyword(s):  
Dna Binding ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Rank Order ◽  
Receptor Ligands ◽  
Free System ◽  
Dioxin Receptor

To reconstitute the molecular mechanisms underlying the cellular response to soluble receptor ligands, we have exploited a cell-free system that exhibits signal- (dioxin-)induced activation of the latent cytosolic dioxin receptor to an active DNA-binding species. The DNA-binding properties of the in vitro-activated form were qualitatively indistinguishable from those of in vivo-activated nuclear receptor extracted from dioxin-treated cells. In vitro activation of the receptor by dioxin was dose dependent and was mimicked by other dioxin receptor ligands in a manner that followed the rank order of their relative affinities for the receptor in vitro and their relative potencies to induce target gene transcription in vivo. Thus, in addition to triggering the initial release of inhibition of DNA binding and presumably allowing nuclear translocation, the ligand appears to play a crucial role in the direct control of the level of functional activity of a given ligand-receptor complex.

Abstract 1340: Disruption of a Hepatocyte Growth Factor/c-Met Receptor Autocrine Loop Severely Impairs the Potency of Pluripotent Adipose Stromal Cells

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Liying Cai ◽  
Brian H Johnstone ◽  
Zhong Liang ◽  
Dmitry Traktuev ◽  
Todd G Cook ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Rank Order ◽  
Residual Activity ◽  
Autocrine Loop ◽  
Major Mode ◽  
Factor C ◽  
Hepatocyte Growth

Background Paracrine stimulation of endogenous repair, rather than direct tissue regeneration, is increasingly accepted as a major mode of therapeutic stem and progenitor cell action; yet, this principle has not been fully established in vivo . Adipose-derived stem cells (ASCs) secrete many factors and promote reperfusion and tissue repair in ischemia models. RNA interference was used to silence the expression of the abundant protein, hepatocyte growth factor (HGF), to determine its contribution to ASC potency in vivo . Methods and Results Dual-cassette lentiviral vectors, expressing GFP and either a small hairpin RNA (shRNA) specific for HGF mRNA (shHGF) or a control sequence (shCtrl), were used to stably transduce ASCs (ASC-shHGF or ASC-shCtrl). ASC-shHGF secreted 5-fold less HGF, which resulted in a reduced ability of these cells to promote survival, proliferation and migration of mature and progenitor endothelial cells in vitro ( p <0.01). HGF knockdown also severely impaired the ability of ASCs to promote reperfusion in a mouse hindlimb ischemia model. Perfusion of the ischemic leg at 15 d in mice treated with ASC-Ctrl was 84±4%, compared to only 69±5% for ASC-shHGF ( p <0.05). Even so, ASC-shHGF retained residual activity as indicated by greater reperfusion ( p <0.05) than with saline treatment (58±6%). Capillary densities in ischemic tissues from each group followed a similar rank order (ASC-Ctrl>ASC-shHGF>saline) ( p <0.05 between each group). While there was no difference in total GFP + cells in ischemic limbs at 5 d after infusion, indicating similar homing potentials, 3-fold fewer ASC-shHGF were present in ischemic tissues at 15 d compared to ASC-shCtrl ( p <0.01). This was accompanied by an increase in TUNEL-positive ASC-shHGF cells (61 ± 0.1%) compared to ASC-Ctrl (41% ± 3.2%) in ischemic tissues at 5 d ( p <0.01); suggesting that attenuated potency of ASC-shHGF was related to reduced survival in ischemic tissues. Conclusions These results indicate that secretion of HGF is critically important for ASC potency. In addition to promoting endogenous repair, the data suggest that an important effect of HGF is autocrine promotion of ASC survival in ischemic tissue. Enhanced donor cell survival is an important goal for increasing the efficacy of cell therapy.

scholarly journals Effects of costimulation of dopamine D1- and D2-like receptors on renal function

1998 ◽  
Vol 275 (4) ◽  
pp. R986-R994 ◽  
Author(s):  
Pedro A. Jose ◽  
Laureano D. Asico ◽  
Gilbert M. Eisner ◽  
Felice Pocchiari ◽  
Claudio Semeraro ◽  
...  
Keyword(s):  
Dopamine Receptor ◽  
Sodium Transport ◽  
Sodium Excretion ◽  
Rank Order ◽  
Sch 23390 ◽  
Urine Flow ◽  
Dopamine Receptor Agonist ◽  
Vasodilatory Effect

In vitro studies have suggested that dopamine D1- and D2-like receptors interact to inhibit renal sodium transport. We used Z-1046, a dopamine receptor agonist with the rank-order potency D3 ≥ D4 > D2 > D5 > D1, to test the hypothesis that D1- and D2-like receptors interact to inhibit renal sodium transport in vivo in anesthetized rats. Increasing doses of Z-1046, administered via the right renal artery, increased renal blood flow (RBF), urine flow, and absolute and fractional sodium excretion without affecting glomerular filtration rate. For determination of the dopamine receptor involved in the renal functional effects of Z-1046, another group of rats received Z-1046 at 2 μg ⋅ kg−1 ⋅ min−1( n = 10) in the presence or absence of the D2-like receptor antagonist domperidone and/or the D1-like antagonist SCH-23390. Domperidone alone had no effect but blocked the Z-1046-mediated increase in urine flow and sodium excretion; it enhanced the increase in RBF after Z-1046. SCH-23390 by itself decreased urine flow and sodium excretion without affecting RBF and blocked the diuretic, natriuretic, and renal vasodilatory effect of Z-1046. We conclude that the renal vasodilatory effect of Z-1046 is D1-like receptor dependent, whereas the diuretic and natriuretic effects are both D1- and D2-like receptor dependent.

scholarly journals Genotoxic and Chemopreventive Effects of Vochysia divergens Leaves (Pantanal, Brazil)

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Pollyanna Francielli de Oliveira ◽  
Suzana Amorim Mendes ◽  
Nathália Oliveira Acésio ◽  
Luis Claudio Kellner Filho ◽  
Leticia Pereira Pimenta ◽  
...  
Keyword(s):  
Protective Effect ◽  
Skin Diseases ◽  
Chemical Constituents ◽  
Test System ◽  
Negative Control ◽  
Control Group ◽  
Xtt Assay ◽  
Vochysia Divergens

The medicinal plant Vochysia divergens is a colonizing tree species of the Pantanal, a unique and little explored wetland region in Brazil. This species is used in folk medicine as syrups and teas to treat respiratory infections, digestive disorders, asthma, scarring, and skin diseases. The objectives of this study were to evaluate the antioxidant, cytotoxic, and genotoxic potential of the ethanolic extract of Vochysia divergens leaves (VdE), as well as the influence of VdE and its major component (the flavone 3′,5-dimethoxy luteolin-7-O-β-glucopyranoside; 3′5 DL) on MMS-induced genotoxicity. The extract significantly reduced the viability of V79 cells in the colorimetric XTT assay at concentrations ≥ 39 μg/mL. A significant increase in micronucleus frequencies was observed in V79 cell cultures treated with VdE concentrations of 160 and 320 μg/mL. However, animals treated with the tested doses of VdE (500, 1000, and 2000 mg/kg b.w.) exhibited frequencies that did not differ significantly from those of the negative control group, indicating the absence of genotoxicity. The results also showed that VdE was effective in reducing MMS-induced genotoxicity at concentrations of 20, 40, and 80 μg/mL in the in vitro test system and at a dose of 15 mg/kg b.w. in the in vivo test system. Its major component 3′5 DL exerted no protective effect, suggesting that it is not responsible for the effect of the extract. The results of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay showed that VdE was able to scavenge 92.6% of free radicals. In conclusion, the results suggest that the protective effect of VdE may be related, at least in part, to the antioxidant activity of its chemical constituents.

scholarly journals Co-Treatment with the Epigenetic Drug, 3-Deazaneplanocin A (DZNep) and Cisplatin after DZNep Priming Enhances the Response to Platinum-Based Therapy in Chondrosarcomas

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4648
Author(s):  
Eva Lhuissier ◽  
Juliette Aury-Landas ◽  
Marion Lenté ◽  
Karim Boumediene ◽  
Catherine Baugé
Keyword(s):  
Tumor Volume ◽  
Mice Model ◽  
Antitumoral Effect ◽  
Viable Cells ◽  
Epigenetic Drug ◽  
Xenograft Mice Model ◽  
Xenograft Mice ◽  
Tumoral Cells

Background: We have previously shown that 3-Deazaneplanocin A (DZNep) induces apoptosis in chondrosarcomas. Herein, we tested whether the combination of this epigenetic drug to a standard anticancer therapy may enhance the response to each drug in these bone tumors. Methods: Two chondrosarcoma cell lines (SW1353 and JJ012) were cultured in the presence of DZNep and/or cisplatin. Cell growth was evaluated by counting viable cells, and apoptosis was determined by Apo2.7 expression by flow cytometry. In vivo, the antitumoral effect of the DZNep/cisplatin combination was assessed through measurements of tumor volume of JJ012 xenografts in nude mice. Results: In vitro, the DZNep/cisplatin combination reduced cell survival and increased apoptosis compared to each drug alone in chondrosarcomas, but not in normal cells (chondrocytes). This enhancement of the antitumoral effect of the DZNep/cisplatin combination required a priming incubation with DZNep before the co-treatment with DZNep/cisplatin. Furthermore, in the chondrosarcoma xenograft mice model, the combination of both drugs more strongly reduced tumor growth and induced more apoptosis in tumoral cells than each of the drugs alone. Conclusion: Our results show that DZNep exposure can presensitize chondrosarcoma cells to a standard anticancer drug, emphasizing the promising clinical utilities of epigenetic-chemotherapeutic drug combinations in the future treatment of chondrosarcomas.

Acoustic Signals from Skeletal Muscle

Physiology ◽  
1990 ◽  
Vol 5 (1) ◽  
pp. 17-21 ◽  
Author(s):  
DT Barry
Keyword(s):  
Skeletal Muscles ◽  
Acoustic Signals ◽  
Skin Surface ◽  
Pressure Waves ◽  
Mechanical Vibrations ◽  
Intrinsic Component ◽  
Measuring Force ◽  
Muscle Sounds

Contracting skeletal muscles emit pressure waves that are audible at the skin surface and are easily recorded with standard microphones both in vivo and in vitro. These muscle sounds are an intrinsic component of the contractile mechanism and are produced by mechanical vibrations at the resonant frequency of the muscle. The sounds are useful in measuring force, fatigue, and mechanical properties of muscle.

scholarly journals Prediction of in Vivo Cytotoxicity of Chemotherapeutic Agents by Their Effect on Malignant Leukocytes in Vitro

Blood ◽  
1967 ◽  
Vol 30 (2) ◽  
pp. 176-188 ◽  
Author(s):  
MARTIN J. CLINE
Keyword(s):  
Test System ◽  
Chemotherapeutic Agents ◽  
Response To Treatment ◽  
In Vitro Test ◽  
Malignant Cells ◽  
Vitro Test ◽  
In Vitro Effects ◽  
In Vivo Cytotoxicity

Abstract In order to develop a test system for predicting the response to chemotherapeutic agents, leukocytes from patients with leukemia and leukolymphosarcoma were cultured in vitro and the effect of several drugs on the incorporation of H3-uridine into ribonucleic acid was measured. Cortisol, vincristine and cytosine arabinoside at concentrations near the therapeutic range produced inhibition of H3-uridine incorporation in sensitive leukocytes. The in vitro effects of 6-mercaptopurine and methotrexate were variable. In 39 trials on 25 patients with leukemia or lymphosarcoma, the in vitro test was used successfully to predict the response to treatment with prednisone and vincristine. It was concluded that the in vitro test system can predict the in vivo cytotoxicity of certain drugs for malignant cells, although it cannot be used to predict the likelihood of the induction of remissions with these drugs.

IS IT POSSIBLE TO IDENTIFY HUMAN PLATELETS IN VITRO AS BEING DESENSITIZED TO PLATELET ACTIVATING FACTOR (PAF-ACETHER,PAF) IN VIVO?

1987 ◽  
Author(s):  
Cs Perger ◽  
A von Felten
Keyword(s):  
Platelet Activating Factor ◽  
Test System ◽  
Human Platelets ◽  
Vacuum Filtration ◽  
Reversible Aggregation ◽  
The Individual ◽  
20 Nm ◽  
And Control

PAF is suggested to be of pathophysiological importance in a variety of diseases. Since platelets exhibit a reduced sensitivity to PAF after a contact with this agent, this behavior may be used as indicator of PAF released into the circulation. In extrinsic asthma, platelets show a diminished reaction to PAF after exposition of the patients to the antigen compared to their own platelets before exposition (Beer and von Felten, Adv. Inflamm. Res. 10:323,1986). We were therefore looking for a test system indicating directly whether platelets had been in contact with PAF.Preparation of PAF-desensitized platelets: Citrated PRP was placed in a cuvette of an aggregometer, and PAF was added in 10 portions at intervals of 10 sec (37oc, constant stirring) to a final concentration of 10 to 100 nM, depending on the individual sensitivity of each platelet preparation. Therby, only a minimal, completely reversible aggregation was registered without any release of serotonin (ST) or 3-thromboglobulin (BTG). Control platelets were pretreated with buffer instead of PAF. Both platelets preparations were kept at 37°C for 45 min. Whereas control platelets showed a secondary aggregation to PAF (5x conc. used for desensitization), PAF-pretreated piatelets were only reversibly aggregated.Sensitivity of PAF-desensitized and control platelets to other platelet agonists: No difference in aggregation, ST-or BTG-relea-se was observed after stimulation with several concentrations of ADP, collagen and arachidonate (p>0.05,n= 41).Binding of 3H-PAF to platelets: PAF-desensitized and control platelets were separated from plasma by filtration through sepharose CL-2B (Pharmacia) in hepes-buffered Tyrode’s solution. After incubation with 3H-PAF, platelets were washed on Whatman 934-AH filters (vacuum filtration). On desensitized and control platelets, we found 175±48 (mean±sd) and 231±70 3H-PAF molecules / platelet respectively after incubation with 5 nM ^h-PAF, 399±36 and 504±66 ^H-PAF molecules / platelet after incubation with 20 nM. In spite of a statistically significant reduction of PAF-binding after desensitization (p<0.01),the variability of PAF-binding between platelets of different individuals is too high to allow a discrimination of normal from PAF-desensitized platelets.

In vitro characterisation of ultrasound-induced heating effects in the mother and fetus: A clinical perspective

Ultrasound ◽  
2020 ◽  
pp. 1742271X2095319
Author(s):  
Stephanie F Smith ◽  
Piero Miloro ◽  
Richard Axell ◽  
Gail ter Haar ◽  
Christoph Lees
Keyword(s):  
Temperature Increase ◽  
Skin Surface ◽  
Maximum Temperature ◽  
Factors Affecting ◽  
Bone Interface ◽  
Heating Effects ◽  
Power Setting ◽  
Lower Temperature

Introduction The quantification of heating effects during exposure to ultrasound is usually based on laboratory experiments in water and is assessed using extrapolated parameters such as the thermal index. In our study, we have measured the temperature increase directly in a simulator of the maternal–fetal environment, the ‘ISUOG Phantom’, using clinically relevant ultrasound scanners, transducers and exposure conditions. Methods The study was carried out using an instrumented phantom designed to represent the pregnant maternal abdomen and which enabled temperature recordings at positions in tissue mimics which represented the skin surface, sub-surface, amniotic fluid and fetal bone interface. We tested four different transducers on a commercial diagnostic scanner. The effects of scan duration, presence of a circulating fluid, pre-set and power were recorded. Results The highest temperature increase was always at the transducer–skin interface, where temperature increases between 1.4°C and 9.5°C were observed; lower temperature rises, between 0.1°C and 1.0°C, were observed deeper in tissue and at the bone interface. Doppler modes generated the highest temperature increases. Most of the heating occurred in the first 3 minutes of exposure, with the presence of a circulating fluid having a limited effect. The power setting affected the maximum temperature increase proportionally, with peak temperature increasing from 4.3°C to 6.7°C when power was increased from 63% to 100%. Conclusions Although this phantom provides a crude mimic of the in vivo conditions, the overall results showed good repeatability and agreement with previously published experiments. All studies showed that the temperature rises observed fell within the recommendations of international regulatory bodies. However, it is important that the operator should be aware of factors affecting the temperature increase.

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