The Relationship Between In Vivo Dermal Penetration Studies in Humans and In Vitro Predictions Using Human Skin

Author(s):  
Simon Wilkinson ◽  
Faith Williams
2004 ◽  
Vol 23 (9) ◽  
pp. 421-430 ◽  
Author(s):  
B Van Ravenzwaay ◽  
E Leibold

In vitro skin penetration rates in rat and man were compared to those obtained in vivo in rats. Saturation of absorption was frequently observed at higher exposure levels in in vitro and in vivo. Lipophilic compounds showed the highest penetration rates through rat skin in vitro. In all cases in vitro dermal penetration through rat skin was higher than in vivo. Thus, the in vitro study may serve as a first tier test. The in vivo data suggest an inverse relationship between molecular weight and the rate of dermal absorption for lipophilic as well as hydrophilic compounds. Rat skin was more permeable to all tested substances than human skin (mean difference 10.9-fold). Thus, the systemic exposure of humans may be significantly overestimated if risk assessment is based only on the results of an in vivo rat study, because human skin is less permeable than rat skin. It would appear, therefore, that an estimate of actual dermal penetration through human skin should be based on the combined use of in vivo and in vitro data, using the following equation: %Human dermal penetration =(%rat in vivo dermal penetration) (See PDF for Formula)


Author(s):  
M.J. Murphy ◽  
R.R. Price ◽  
J.C. Sloman

The in vitro human tumor cloning assay originally described by Salmon and Hamburger has been applied recently to the investigation of differential anti-tumor drug sensitivities over a broad range of human neoplasms. A major problem in the acceptance of this technique has been the question of the relationship between the cultured cells and the original patient tumor, i.e., whether the colonies that develop derive from the neoplasm or from some other cell type within the initial cell population. A study of the ultrastructural morphology of the cultured cells vs. patient tumor has therefore been undertaken to resolve this question. Direct correlation was assured by division of a common tumor mass at surgical resection, one biopsy being fixed for TEM studies, the second being rapidly transported to the laboratory for culture.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yi Xin She ◽  
Qing Yang Yu ◽  
Xiao Xiao Tang

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Pengfei Liu ◽  
Jing Yuan ◽  
Yetong Feng ◽  
Xin Chen ◽  
Guangsuo Wang ◽  
...  

AbstractFerroptosis is a novel type of programmed cell death, which is different from apoptosis and autophagic cell death. Recently, ferroptosis has been indicated to contribute to the in vitro neurotoxicity induced by isoflurane, which is one of the most common anesthetics in clinic. However, the in vivo position of ferroptosis in isoflurane-induced neurotoxicity as well as learning and memory impairment remains unclear. In this study, we mainly explored the relationship between ferroptosis and isoflurane-induced learning and memory, as well as the therapeutic methods in mouse model. Our results indicated that isoflurane induced the ferroptosis in a dose-dependent and time-dependent manner in hippocampus, the organ related with learning and memory ability. In addition, the activity of cytochrome c oxidase/Complex IV in mitochondrial electron transport chain (ETC) was increased by isoflurane, which might further contributed to cysteine deprivation-induced ferroptosis caused by isoflurane exposure. More importantly, isoflurane-induced ferroptosis could be rescued by both ferroptosis inhibitor (ferrostatin-1) and mitochondria activator (dimethyl fumarate), which also showed effective therapeutic action against isoflurane-induced learning and memory impairment. Taken together, our data indicate the close association among ferroptosis, mitochondria and isoflurane, and provide a novel insight into the therapy mode against isoflurane-induced learning and memory impairment.


2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Xiaoping Zhang ◽  
Dan Li ◽  
Chengyou Jia ◽  
Haidong Cai ◽  
Zhongwei Lv ◽  
...  

Abstract Background Papillary thyroid cancer (PTC) is the most common type of cancer of the endocrine system. Long noncoding RNAs (lncRNAs) are emerging as a novel class of gene expression regulators associated with tumorigenesis. Through preexisting databases available for differentially expressed lncRNAs in PTC, we uncovered that lncRNA OIP5-AS1 was significantly upregulated in PTC tissues. However, the function and the underlying mechanism of OIP5-AS1 in PTC are poorly understood. Methods Expression of lncRNA OIP5-AS1 and miR-98 in PTC tissue and cells were measured by quantitative real-time PCR (qRT-PCR). And expression of METTL14 and ADAMTS8 in PTC tissue and cells were measured by qRT-PCR and western blot. The biological functions of METTL14, OIP5-AS1, and ADAMTS8 were examined using MTT, colony formation, transwell, and wound healing assays in PTC cells. The relationship between METTL14 and OIP5-AS1 were evaluated using RNA immunoprecipitation (RIP) and RNA pull down assay. And the relationship between miR-98 and ADAMTS8 were examined by luciferase reporter assay. For in vivo experiments, a xenograft model was used to investigate the effects of OIP5-AS1 and ADAMTS8 in PTC. Results Functional validation revealed that OIP5-AS1 overexpression promotes PTC cell proliferation, migration/invasion in vitro and in vivo, while OIP5-AS1 knockdown shows an opposite effect. Mechanistically, OIP5-AS1 acts as a target of miR-98, which activates ADAMTS8. OIP5-AS1 promotes PTC cell progression through miR-98/ADAMTS8 and EGFR, MEK/ERK pathways. Furthermore, RIP and RNA pull down assays identified OIP5-AS1 as the downstream target of METTL14. Overexpression of METTL14 suppresses PTC cell proliferation and migration/invasion through inhibiting OIP5-AS1 expression and regulating EGFR, MEK/ERK pathways. Conclusions Collectively, our findings demonstrate that OIP5-AS1 is a METTL14-regulated lncRNA that plays an important role in PTC progression and offers new insights into the regulatory mechanisms underlying PTC development.


1970 ◽  
Vol 50 (3) ◽  
pp. 557-562 ◽  
Author(s):  
J. E. TROELSEN

Forage of six pure species was harvested for hay at several maturity stages during four years. The digestible energy content of 102 different lots of hay was determined by feeding to four groups of sheep during the same period, and by in vitro digestions and energy analysis of the undigested residues. The relationship between digestible energy content assayed by the two methods was highly significant (r = 0.85) and did not differ between years and species. Exclusion from regression of the hays containing less than 2 or more than 3 digestible kcal/g revealed that the in vitro assay could reproduce the in vivo digestible energy value with a standard deviation of 0.31 in over 70% of the hays. This represented the maturity and quality range of forage commonly fed to cattle and sheep. The in vitro assay therefore appeared promising for commercial quality determinations.


1980 ◽  
Vol 9 (4) ◽  
pp. 179-183 ◽  
Author(s):  
H L Stark ◽  
A Al-Haboubi

The relationships of width, thickness, volume and load to extension for human skin in vitro are reported. The specimens tested exhibited a low stiffness phase followed by a high stiffness phase. Volume rose than fell back to the initial volume at approximately the end of the low stiffness phase, and continued on falling to a final reduction of about 20 per cent at failure. Width decreased throughout, showing a maximum rate of reduction at approximately the end of the low stiffness phase. Thickness increased at a rate which also was maximum at the end of the low stiffness phase. The specimens used were long compared with their width and thickness thus offering no constraint to lateral contraction. An interpretation of this data in respect of the behaviour of the collagen fibre matrix is postulated.


Sign in / Sign up

Export Citation Format

Share Document