Paraquat Poisoning by Skin Absorption: A Review

1988 ◽  
Vol 7 (1) ◽  
pp. 15-19 ◽  
Author(s):  
J.G. Smith
Keyword(s):  
Human Skin ◽  
Animal Experiments ◽  
Systemic Absorption ◽  
In Vitro Tests ◽  
Skin Damage ◽  
Fatal Poisoning ◽  
Head Restraint ◽  
Paraquat Poisoning

All reported cases of paraquat poisoning by absorption through the skin are briefly reviewed. It is concluded that, while paraquat cannot be absorbed significantly through intact human skin, damage to the skin, either by paraquat itself or by other means, will permit greater systemic absorption and possibly poisoning. The lowest known concentration of paraquat to result in fatal poisoning through the skin is 5 g/l. Animal experiments with paraquat are also reviewed. The fact that the reported lethal dermal dose of paraquat in rats is slightly less than the oral dose is probably due to the lack of head restraint on the rats in the dermal dosing experiments. In vivo and in vitro tests on human skin at concentrations of 9 g/l and 5 g/l did not result in significant absorption of paraquat through the skin but in these experiments the skin was intact.

Development and Test of an Extendable Endoprosthesis for Bone Reconstruction in the Leg

1994 ◽  
Vol 17 (3) ◽  
pp. 155-162 ◽  
Author(s):  
G.J. Verkerke ◽  
H. Schraffordt Koops ◽  
R.P.H. Veth ◽  
H.J. Grootenboer ◽  
L.J. De Boer ◽  
...  
Keyword(s):  
Magnetic Field ◽  
External Magnetic Field ◽  
Growth Plate ◽  
Animal Experiments ◽  
Bone Tumour ◽  
In Vitro Tests ◽  
Bone Reconstruction ◽  
Malignant Bone Tumour

A malignant bone tumour may develop in the femur of a child. In the majority of cases it will be necessary to resect the bone involved, growth plate and adjacent tissues. A modular endoprosthetic system has been developed which can be extended non-invasively to bridge the defect resulting from such a resection. Elongation is achieved by using an external magnetic field. In vitro tests with a prototype showed that the lengthening element met all requirements. Six animal experiments showed that the lengthening element also functioned in vivo.

scholarly journals Topical Delivery of Carvedilol Loaded Nano-Transfersomes for Skin Cancer Chemoprevention

Pharmaceutics ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1151
Author(s):  
Mengbing Chen ◽  
Md Abdullah Shamim ◽  
Ayaz Shahid ◽  
Steven Yeung ◽  
Bradley T. Andresen ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Cancer Chemoprevention ◽  
Tween 80 ◽  
Topical Delivery ◽  
Human Keratinocytes ◽  
Systemic Absorption ◽  
Skin Damage ◽  
Β Blocker

The β-blocker carvedilol has been shown to prevent skin carcinogenesis in vitro and in vivo. Since systemic absorption of the β-blocker may cause cardiovascular disturbance, we developed a carvedilol loaded transfersome for skin-targeted delivery. Transfersomes were prepared using phospholipids and surfactants at various ratios and characterized. One formulation (F18) selected for further analysis was composed of carvedilol, soy phosphatidylcholine, and Tween-80 at a ratio of 1:3:0.5, which had a particle size of 115.6 ± 8.7 nm, a zeta potential of 11.34 ± 0.67 mV, and an encapsulation efficiency of 93.7 ± 5.1%. F18 inhibited EGF-induced neoplastic transformation of mouse epidermal JB6 P+ cells at non-toxic concentrations, while only high concentrations induced cytotoxicity in JB6 P+ and human keratinocytes HaCaT. Compared to the free drug, F18 released through the dialysis membrane and permeated through the porcine ear skin at a slower rate, but similarly depositing the drug in the epidermis and dermis of the skin. Consistently, surface application of F18 on reconstructed full-thickness human skin showed slower drug permeation, while it suppressed ultraviolet-induced DNA damage, inflammatory gene expression, and apoptosis. These data indicate that transfersome is a promising topical delivery system of carvedilol for preventing ultraviolet-induced skin damage and carcinogenesis.

scholarly journals Luteolin Prevents UVB-Induced Skin Photoaging Damage by Modulating SIRT3/ROS/MAPK Signaling: An in vitro and in vivo Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Mu ◽  
Huisheng Ma ◽  
Hong Chen ◽  
Xiaoxia Zhang ◽  
Mengyi Ye
Keyword(s):  
Animal Experiments ◽  
Mapk Signaling ◽  
Dermal Fibroblasts ◽  
In Vivo Studies ◽  
Uvb Radiation ◽  
Skin Damage ◽  
Cellular Protection ◽  
Uvb Irradiation

The aim of this study was to investigate the role of luteolin in the mechanism of ultraviolet radiation B (UVB)-induced photoaging. An in vivo photoaging model was established using UVB irradiation of bare skin on the back of rats, and an in vitro photoaging model was established using UVB irradiation of human dermal fibroblasts (HDF). Skin damage was observed using hematoxylin-eosin (HE) and Masson staining, skin and cellular reactive oxygen species (ROS) levels were detected by DHE and DCF fluorescent probes, mitochondrial membrane potential was detected by JC-1 staining, and protein expressions were detected by immunofluorescence and Western Blot. Results from animal experiments showed that luteolin reduced UVB-induced erythema and wrinkle formation. Results from cellular assays showed that luteolin inhibited UVB-induced decrease in cell viability. In addition, in vitro and in vivo experiments showed that luteolin reduced oxidative stress levels, decreased activation of matrix metalloproteinases (MMPs) and increased collagen expression. Continued cellular experiments using 3-TYP, an inhibitor of Sirtuin 3 (SIRT3), revealed a loss of cellular protection by luteolin and a decrease in collagen, suggesting that luteolin acts by targeting and promoting SIRT3. luteolin is involved in the protection of skin cells against UVB radiation-induced ageing via the SIRT3/ROS/mitogen-activated protein kinases (MAPK) axis and it may be a promising therapeutic agent for the prevention of UVB photoaging.

Some aspects of metal oxide nanoparticles toxicity assessment on cell cultures as exemplified by NiO and Mn3O4

2017 ◽  
pp. 35-43 ◽  
Author(s):  
I. А. Minigalieva ◽  
T. V. Bushueva ◽  
V. G. Panov ◽  
A. N. Varaksin ◽  
V. Ya. Shur ◽  
...  
Keyword(s):  
Culture Media ◽  
Cell Damage ◽  
Metal Oxide Nanoparticles ◽  
Animal Experiments ◽  
Toxicity Assessment ◽  
In Vitro Tests ◽  
Fetal Bovine ◽  
Nio Nps

Comparative and combined damaging actions of NiO and Mn3O4 anoparticles were estimated on cultures of different established human cell lines. It was found out that the addition of the fetal bovine serum (FBS) to the culture media ,used in the investigation, renders NiO-NPs and, to even a greater extent, Mn3O4-NPs exponentially soluble while without FBS their dissolution was extremely low. Along with it, sedimentation of those MeO-NPs caused by their aggregation noticeably slowed down in the presence of the same FBS. The dependence of cell damage on the MeO-NPs concentration was found out, at a higher cytotoxicity of Mn3O4-NP as compared to NiO-NP. Thus, comparative assessment of NPs non-specific toxicity previously obtained in animal experiments was reproduced in the «in vitro» tests. However, with respect to manganese-specific brain damage «in vivo» discovered previously in sub-chronic intoxication with the same MeO-NPs, the present «in vitro» experiment on neurons only showed a certain enhancing effect of Mn3O4-NP on the action of NiO-NP, but the role of NiO-NP in the combination prevailed.

scholarly journals The Beneficial Effect of Rosmarinic Acid on Benzophenone-3-Induced Alterations in Human Skin Fibroblasts

2021 ◽  
Vol 22 (21) ◽  
pp. 11451
Author(s):  
Anna Galicka ◽  
Joanna Sutkowska-Skolimowska
Keyword(s):  
Human Skin ◽  
Rosmarinic Acid ◽  
Type I Collagen ◽  
Skin Fibroblasts ◽  
Percutaneous Penetration ◽  
Systemic Absorption ◽  
Type I ◽  
Human Skin Fibroblasts

Benzophenone-3 (BP-3) is one of the most widely used chemical sunscreens. The results of many in vitro and in vivo tests confirm its high percutaneous penetration and systemic absorption, which question the safety of its wide use. The aim of our research was to assess the effect of this compound on components of the skin extracellular matrix, and to investigate whether rosmarinic acid (RA) could reduce BP-3-induced changes in human skin fibroblasts. BP-3 used at concentrations of 0.1–100 µM caused a number of unfavorable changes in the level of type I collagen, decorin, sulfated glycosaminoglycans, hyaluronic acid, elastin, and expression or activity of matrix metalloproteinases (MMP-1, MMP-2), elastase and hyaluronidase. Moreover, the intracellular retention of collagen was accompanied by changes in the expression of proteins modifying and controlling the synthesis and secretion of this protein. Most importantly, RA at a concentration of 100 µM significantly reduced or completely abolished the adverse effects of BP-3. Based on these findings, it can be concluded that this polyphenol may provide effective protection against BP-3-induced disturbances in skin cells, which may have important clinical implications.

Comparison of High Purity Factor IX Concentrates and a Prothrombin Complex Concentrate in a Canine Model of Thrombogenicity

1991 ◽  
Vol 66 (05) ◽  
pp. 609-613 ◽  
Author(s):  
I R MacGregor ◽  
J M Ferguson ◽  
L F McLaughlin ◽  
T Burnouf ◽  
C V Prowse
Keyword(s):  
High Purity ◽  
Time Course ◽  
Prothrombin Complex Concentrate ◽  
Degradation Products ◽  
Canine Model ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Albumin Infusion

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

A Comparison of the in Vitro and in Vivo Thrombogenic Activity of Factor IX Concentrates Using Stasis (Wessler) and Non-Stasis Rabbit Models

1980 ◽  
Vol 44 (02) ◽  
pp. 081-086 ◽  
Author(s):  
C V Prowse ◽  
A E Williams
Keyword(s):  
Platelet Rich Plasma ◽  
Thrombus Formation ◽  
Factor Ix ◽  
Coagulation System ◽  
In Vitro Tests ◽  
Clinical Use ◽  
Low Activity

SummaryThe thrombogenic effects of selected factor IX concentrates were evaluated in two rabbit models; the Wessler stasis model and a novel non-stasis model. Concentrates active in either the NAPTT or TGt50 in vitro tests of potential thrombogenicity, or both, caused thrombus formation in the Wessler technique and activation of the coagulation system in the non-stasis model. A concentrate with low activity in both in vitro tests did not have thrombogenic effects in vivo, at the chosen dose. Results in the non-stasis model suggested that the thrombogenic effects of factor IX concentrates may occur by at least two mechanisms. A concentrate prepared from platelet-rich plasma and a pyrogenic concentrate were also tested and found to have no thrombogenic effect in vivo.These studies justify the use of the NAPTT and TGt50 in vitro tests for the screening of factor IX concentrates prior to clinical use.

Inhibition of Fibrinolysis and Fibrinogenolysis in Man: Comparison of ε-Aminocaproic Acid and Kallikrein Inhibitor

1963 ◽  
Vol 10 (01) ◽  
pp. 106-119 ◽  
Author(s):  
E Beck ◽  
R Schmutzler ◽  
F Duckert ◽  
Keyword(s):  
Aminocaproic Acid ◽  
Side Reactions ◽  
In Vitro Tests ◽  
Factor V ◽  
Clinical Use ◽  
Strong Inhibitor ◽  
Kallikrein Inhibitor ◽  
Therapeutic Possibilities

SummaryInhibitor of kallikrein and trypsin (KI) extracted from bovine parotis was compared with ε-aminocaproic acid (EACA): both substances inhibit fibrinolysis induced with streptokinase. EACA is a strong inhibitor of fibrinolysis in concentrations higher than 0, 1 mg per ml plasma. The same amount and higher concentrations are not able to inhibit completely the proteolytic-side reactions of fibrinolysis (fibrinogenolysis, diminution of factor V, rise of fibrin-polymerization-inhibitors). KI inhibits well proteolysis of plasma components in concentrations higher than 2,5 units per ml plasma. Much higher amounts of KI are needed to inhibit fibrinolysis as demonstrated by our in vivo and in vitro tests.Combination of the two substances for clinical use is suggested. Therapeutic possibilities are discussed.

Role of in vivo and in vitro Tests in the Diagnosis of Severe Cutaneous Adverse Reactions (SCAR) to Drug

2019 ◽  
Vol 25 (36) ◽  
pp. 3872-3880 ◽  
Author(s):  
Marcel M. Bergmann ◽  
Jean-Christoph Caubet
Keyword(s):  
Adverse Reactions ◽  
Lymphocyte Transformation ◽  
Stevens Johnson Syndrome ◽  
In Vitro Tests ◽  
High Morbidity ◽  
Patch Tests ◽  
Severe Cutaneous Adverse Reactions ◽  
Cutaneous Adverse Reactions

Severe cutaneous adverse reactions (SCAR) are life-threatening conditions including acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Diagnosis of causative underlying drug hypersensitivity (DH) is mandatory due to the high morbidity and mortality upon re-exposure with the incriminated drug. If an underlying DH is suspected, in vivo test, including patch tests (PTs), delayed-reading intradermal tests (IDTs) and in vitro tests can be performed in selected patients for which the suspected culprit drug is mandatory, or in order to find a safe alternative treatment. Positivity of in vivo and in vitro tests in SCAR to drug varies depending on the type of reaction and the incriminated drugs. Due to the severe nature of these reactions, drug provocation test (DPT) is highly contraindicated in patients who experienced SCAR. Thus, sensitivity is based on positive test results in patients with a suggestive clinical history. Patch tests still remain the first-line diagnostic tests in the majority of patients with SCAR, followed, in case of negative results, by delayed-reading IDTs, with the exception of patients with bullous diseases where IDTs are still contra-indicated. In vitro tests have shown promising results in the diagnosis of SCAR to drug. Positivity is particularly high when the lymphocyte transformation test (LTT) is combined with cytokines and cytotoxic markers measurement (cyto-LTT), but this still has to be confirmed with larger studies. Due to the rarity of SCAR, large multi-center collaborative studies are needed to better study the sensitivity and specificity of in vivo and in vitro tests.

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