scholarly journals Studies on the Survival of Incompatible Cells in Patients with Hypogammaglobulinemia

Blood ◽  
1959 ◽  
Vol 14 (1) ◽  
pp. 24-36 ◽  
Author(s):  
HUGH CHAPLIN
Keyword(s):  
Paper Electrophoresis ◽  
In Vitro Tests ◽  
Antibody Activity ◽  
In Vitro Test ◽  
Red Cell ◽  
Survival Times ◽  
Wide Range ◽  
Group B

Abstract 1. Four adult patients are described whose sera showed a complete lack of gamma globulin by paper electrophoresis. 2. All four patients might have been considered "universal recipients" because of the absence of isohemagglutinins on routine laboratory tests. 3. Weak isohemagglutinins were detectable in the sera from three of the four subjects when the sensitivity of the in vitro test was increased. 4. Following intravenous administration of 4 ml. of ABO-incompatible cells, red cell survival was shortened in all of the patients, with a wide range of half-survival times from <10 minutes to as long as 9 days. 5. Although in vitro tests for antibody activity revealed no qualitative differences among the sera from the three patients with detectable isohemagglutinins, two different mechanisms of red cell removal were observed, one which entailed nearly equal activity by both liver and spleen, the other being primarily a function of the spleen. 6. The survival of incompatible cells under conditions of antibody "excess" and antibody "insufficiency" was compared in one of the patients. The findings emphasize the sensitivity of in vivo survival studies employing small volumes of incompatible cells to detect minute quantities of circulating antibody. 7. A fall in anti-A titer following the administration of group B cells to one hypogammaglobulinemic subject is interpreted as a possible in vivo example of the absorption of "cross-reacting" antibody in the ABO system. 8. In the light of the in vivo and in vitro findings, none of the 4 hypogammaglobulinemic patients in the present series could be categorized as "universal recipients."

scholarly journals New Triazole NT-a9 Has Potent Antifungal Efficacy against Cryptococcus neoformans In Vitro and In Vivo

2019 ◽  
Vol 64 (2) ◽  
Author(s):  
Ren-Yi Lu ◽  
Ting-Jun-Hong Ni ◽  
Jing Wu ◽  
Lan Yan ◽  
Quan-Zhen Lv ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Amphotericin B ◽  
Pathogenic Fungi ◽  
Control Group ◽  
Survival Times ◽  
Content Type ◽  
Fungal Burden ◽  
Wide Range

ABSTRACT In the past decades, the incidence of cryptococcosis has increased dramatically, which poses a new threat to human health. However, only a few drugs are available for the treatment of cryptococcosis. Here, we described a leading compound, NT-a9, an analogue of isavuconazole, that showed strong antifungal activities in vitro and in vivo. NT-a9 showed a wide range of activities against several pathogenic fungi in vitro, including Cryptococcus neoformans, Cryptococcus gattii, Candida albicans, Candida krusei, Candida tropicalis, Candida glabrata, and Candida parapsilosis, with MICs ranging from 0.002 to 1 μg/ml. In particular, NT-a9 exhibited excellent efficacy against C. neoformans, with a MIC as low as 0.002 μg/ml. NT-a9 treatment resulted in changes in the sterol contents in C. neoformans, similarly to fluconazole. In addition, NT-a9 possessed relatively low cytotoxicity and a high selectivity index. The in vivo efficacy of NT-a9 was assessed using a murine disseminated-cryptococcosis model. Mice were infected intravenously with 1.8 × 106 CFU of C. neoformans strain H99. In the survival study, NT-a9 significantly prolonged the survival times of mice compared with the survival times of the control group or the isavuconazole-, fluconazole-, or amphotericin B-treated groups. Of note, 4 and 8 mg/kg of body weight of NT-a9 rescued all the mice, with a survival rate of 100%. In the fungal-burden study, NT-a9 also significantly reduced the fungal burdens in brains and lungs, while fluconazole and amphotericin B only reduced the fungal burden in lungs. Taken together, these data suggested that NT-a9 is a promising antifungal candidate for the treatment of cryptococcosis infection.

scholarly journals Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action

2020 ◽  
Author(s):  
Katherine E. Chapman ◽  
Eleanor C. Wilde ◽  
Fiona M. Chapman ◽  
Jatin R. Verma ◽  
Ume-Kulsoom Shah ◽  
...  
Keyword(s):  
Cell Line ◽  
Human Cell Line ◽  
Test System ◽  
In Vitro Tests ◽  
Correct Identification ◽  
In Vitro Test ◽  
Human Lymphoblastoid Cell ◽  
Carcinogenic Potential

Abstract Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound’s subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001–770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the “misleading” in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.

Comparison of methods for measurement of the pressure exerted by knitted fabrics

2016 ◽  
Vol 87 (17) ◽  
pp. 2117-2126 ◽  
Author(s):  
Małgorzata Cieślak ◽  
Agnieszka Karaszewska ◽  
Ewa Gromadzińska ◽  
Izabela Jasińska ◽  
Irena Kamińska
Keyword(s):  
In Vitro Tests ◽  
Knitted Fabric ◽  
In Vitro Test ◽  
Knitted Fabrics ◽  
Weft Knitted Fabric ◽  
In Vivo Tests ◽  
Vitro Test ◽  
Warp Knitted Fabric

The article presents the results of measurements of pressure exerted by two model knitted products – bands with different structure (WI jersey weft-knitted fabric and WII openwork warp-knitted fabric). The tests were carried out with using the I-Scan system (in vivo and in vitro tests) and the STM 579 device (in vitro test). A comparative analysis of the in vivo and in vitro results for the I-Scan method and in vitro results for the I-Scan and STM 579 method was performed. It was found that the pressure values are lower for openwork warp-knitted fabric than for jersey weft-knitted fabric both in the case of the in vitro and in vivo tests, and the values of pressure for the same band are higher in the case of the in vitro tests.

scholarly journals The Removal of in Vitro Damaged Erythrocytes from the Circulation of Normal and Splenectomized Rats

Blood ◽  
1965 ◽  
Vol 26 (1) ◽  
pp. 49-62 ◽  
Author(s):  
JOHN E. ULTMANN ◽  
CLARA S. GORDON
Keyword(s):  
Life Span ◽  
Osmotic Fragility ◽  
Reticuloendothelial System ◽  
Red Cells ◽  
In Vitro Tests ◽  
Red Cell ◽  
Cell Integrity ◽  
Prolonged Incubation

Abstract The in vitro alterations and in vivo fate of erythrocytes treated with N-ethylmaleimide or subjected to prolonged incubation were studied in normal and splenectomized rats. Minimal injury (20 µM NEM/ml. RBC) resulted in red cells with decreased osmotic fragility and increased plasticity; however, mechanical fragility was significantly increased. These cells were removed with a half-time of 78 minutes, mainly by splenic sequestration, and splenectomy prolonged their life span. Incubation at 37 C. for 21 hours produced erythrocytes with increased osmotic and mechanical fragility and decreased plasticity. Erythrocyte clearance was more rapid (T½ = 59 minutes), with spleen and liver removing approximately an equal number of cells and splenectomy having little effect on red cell life span. With severe injury (40 µM NEM/ml. RBC), all three in vitro measurements showed marked alterations, red cell removal was rapid (T½ = 35 minutes), mainly by hepatic sequestration, and clearance was unaffected by splenectomy. The present studies have shown that chemical injury or prolonged incubation lead to profound changes in in vitro tests of red cell integrity, the mechanical fragility predicting most closely the subsequent in vivo events. Although the entire reticuloendothelial system appears to participate in red cell removal, the spleen and liver are the major sites of sequestration in the rat. The splenic removal predominates with minimally injured cells, hepatic removal with moderately and severely altered cells. The type of injury appears to be of less significance than the degree of injury of the red cells.

scholarly journals Single-unit transfusions of RBC enzymatically converted from group B to group O to A and O normal volunteers

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1383-1388 ◽  
Author(s):  
LL Lenny ◽  
R Hurst ◽  
J Goldstein ◽  
LJ Benjamin ◽  
RL Jones
Keyword(s):  
Single Unit ◽  
Small Volume ◽  
Survival Times ◽  
Chronic Anemia ◽  
Group A ◽  
Alpha Galactosidase ◽  
Group B ◽  
Sustained Increase

Abstract Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha- galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.

In Vitro Toxicology and the Test Guidelines

1996 ◽  
Vol 24 (3) ◽  
pp. 435-438
Author(s):  
Kimmo Louekari
Keyword(s):  
Cost Effective ◽  
Test Methods ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
In Vitro Methods ◽  
Effective Manner ◽  
Genotoxic Carcinogens ◽  
Vitro Test

Ethical, economical and scientific considerations should encourage the development of alternative and in vitro test methods. Before their adoption, in vitro methods need to be validated and scientifically justified. Demand for rigorous validation schemes for in vitro tests must be emphasised, even more than in the case of in vivo tests. The OECD has adopted in vitro guidelines for testing genotoxicity; several endpoints and mechanisms can be studied in a cost-effective manner in vitro. Similar advantages could be afforded if acute irritation and corrosion, as well as the non-genotoxic carcinogenic effects of chemicals, could be studied in vitro. Evaluation of the validation status of various methods used to study non-genotoxic carcinogens was begun by the Nordic Working Group on In Vitro Methods for Non-genotoxic Mechanisms in 1996. In some established OECD test guidelines (for example, the dermal irritation/corrosion test), there is already room for the application of in vitro methods which have not been formally validated. In January 1996, the OECD Workshop on Harmonisation of Validation and Acceptance Criteria for Alternative Toxicological Test Methods set the basis for internationally acceptable principles to be followed in the validation of in vitro test methods.

scholarly journals Predicting and Testing Bioavailability of Magnesium Supplements

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1663 ◽  
Author(s):  
Laura Blancquaert ◽  
Chris Vervaet ◽  
Wim Derave
Keyword(s):  
Serum Magnesium ◽  
Area Under The Curve ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Beneficial Effects ◽  
Dissolution Tests ◽  
Acute Ingestion ◽  
In Vivo Testing

Despite the presumption of the beneficial effects of magnesium supplementation, little is known about the pharmacokinetics of different magnesium formulations. We aimed to investigate the value of two in vitro approaches to predict bioavailability of magnesium and to validate this in subsequent in vivo testing. In vitro assessment of 15 commercially available magnesium formulations was performed by means of a Simulator of the Human Intestinal Microbial Ecosystem (SHIME®) and by dissolution tests. Two magnesium formulations with contrasting bioavailability prediction from both in vitro tests (best vs. worst) were selected for in vivo testing in 30 subjects. In vivo bioavailability was compared following one acute ingestion by monitoring blood magnesium concentrations up to 6 h following intake. The in vitro tests showed a very wide variation in absorption and dissolution of the 15 magnesium products. In the in vivo testing, a significant different serum magnesium absorption profile was found up to 4 h following supplement ingestion for the two supplements with opposing in vitro test results. Moreover, maximal serum magnesium increase and total area under the curve were significantly different for both supplements (+6.2% vs. +4.6% and 6.87 vs. 0.31 mM.min, respectively). Collectively, poor bioaccessibility and bioavailability in the SHIME model clearly translated into poor dissolution and poor bioavailability in vivo. This provides a valid methodology for the prediction of in vivo bioavailability and effectiveness of micronutrients by specific in vitro approaches.

scholarly journals IMMUNOREACTIONS INVOLVING PLATELETS

1958 ◽  
Vol 107 (5) ◽  
pp. 711-729 ◽  
Author(s):  
N. Raphael Shulman
Keyword(s):  
Plasma Concentration ◽  
Complement Fixation ◽  
In Vitro Tests ◽  
Antibody Activity ◽  
Minimal Amount ◽  
Thrombocytopenic Purpura ◽  
Safe Method ◽  
In Vivo Tests

Regulated intravenous doses of quinidine were given to patients with the antibody of quinidine purpura to produce controlled thrombocytopenia without clinical sequelae. The degree of thrombocytopenia and the rate at which it developed were dependent on the relative plasma concentration of quinidine and antibody. By relating in vivo changes in platelet levels to concurrent in vitro tests for antibody activity and to quantitative relationships between reactants determined in Papers I and III of this series, it was concluded that the amount of antibody which attaches to platelets when thrombocytopenia develops is insufficient to cause complement fixation or platelet agglutination. Platelets do not appear to be destroyed directly by reaction with antibody in vivo. The minimal amount of antibody which does attach to platelets in vivo appears to increase their susceptibility to the usual mechanisms of sequestration. Megakaryocytes and blood vessels do not appear to be affected directly by the antibody which causes quinidine purpura, and hemorrhagic manifestations of the disease appear to be consequent to changes in platelets alone. A safe method of performing in vivo tests for the presence of an antibody of drug purpura is described. The implications of the present work in idiopathic thrombocytopenic purpura are discussed.

Regulatory Perspective on in Vitro Assays as Predictors of Phototoxicity and Photo Co-Carcinogenicity

1998 ◽  
Vol 17 (5) ◽  
pp. 571-575 ◽  
Author(s):  
Amy L. Ellis
Keyword(s):  
Mammalian Cells ◽  
Hairless Mouse ◽  
In Vitro Assays ◽  
In Vitro Tests ◽  
Drug Products ◽  
Drug Classes ◽  
Wide Range ◽  
Regulatory Perspective

Drugs from a variety of chemical classes used for a wide range of therapeutic indications can be photosensitizers in humans. Several drugs are phototoxic in animal models as well; there are no nonclinical data for many. In vitro tests have been developed as predictors of phototoxicity and although they have been used as screens, none have replaced the in vivo tests done in rodents (usually mice or guinea pigs) since these have been good predictors of clinical phototoxicity. Some phototoxic drug classes are co-carcinogens with ultraviolet radiation (UVA and/or UVB) in hairless mice, specifically psoralens, retinoids, and fluo-roquinolones. Treatment with 8-methoxypsoralen and ultraviolet A radiation for psoriasis is also carcinogenic in humans. It has been suggested that in vitro photogenotoxicity assays using microorganisms or mammalian cells may be predictive of photo co-carcinogenicity. Some attractions of these in vitro assays, compared to the hairless mouse photo co-carcinogenicity assay, are their generally shorter duration and lower cost as well as reducing the number of animals used in research. Currently, personnel at the Food and Drug Administration (FDA) are examining the available data on phototoxicity, photogenotoxicity, and photo co-carcinogenicity to determine how this information can best be used toregulate and label drug products, and considering which assays should be recommended under specific circumstances.

scholarly journals In vivo toxicity of a new antifungal agent 2,4-dithiophenoxy-1-iodo-4-bromo benzene: a follow up on our in vitro study / In vivo toksičnost novoga antimikotika 2,4-ditiofenoksi-1-jodo-4-bromobenzena: proširenje in vitro istraživanja

2015 ◽  
Vol 66 (1) ◽  
pp. 63-72 ◽  
Author(s):  
Aysun Kılıç Süloğlu ◽  
Evrim Koçkaya ◽  
Elif Karacaoğlu ◽  
Güldeniz Selmanoğlu ◽  
Elif Loğoğlu
Keyword(s):  
Antifungal Agent ◽  
Fungal Infections ◽  
In Vitro Study ◽  
Female Rats ◽  
In Vitro Tests ◽  
In Vitro Test ◽  
Benzene Derivative ◽  
New Drug

Abstract Triazole fungicide fluconazole has become the most widely used antifungal agent in the world, mainly because of its ability to penetrate well into body fluids and tissues. However, it has been reported to interact with many drugs and because of its common use, the risk of resistance to fluconazole increases. This calls for new anti-fungal drugs that would be able to replace it. In 2006, a new thialo benzene derivative - 2,4-dithiophenoxy-1-iodo-4-bromo benzene (C18H12S2IBr) - was synthesised with a carbon backbone similar to fluconazole, and, according to the early in vitro tests, much greater efficiency. Followed an in vitro test of its cytotoxicity, in which the new drug showed promising results as an alternative to fluconazole. The aim of this study was take the next step and test C18H12S2IBr toxicity in vivo. We opted for a four-week test on Wistar rats, in which the new antifungal agent was orally applied at doses two and a half and five times lower than those of fluconazole. There were no changes in daily food and water consumption, but weight gain in female rats and relative organ weights changed in the treated groups, pointing to sex-related differences in drug metabolism and effects. Fluconazole significantly increased leukocytes and lowered neutrophils whereas C18H12S2IBr did not, while other haematological changes in respect to the vehicle control were similar between the treated groups. Differences in cytochrome c in the liver and kidney suggested greater apoptotic effect of the new drug, but interpretation remains inconclusive, considering that other key indicators (biochemistry and histopathology) do not support greater toxicity. Considering that C18H12S2IBr is more active at lower concentrations and has comparable toxic effects to fluconazole in rats, this new compound shows some promise in the treatment of fungal infections. Future, more detailed animal studies are needed, that will include drug interactions and molecular toxicity pathways. If the results are promising, clinical studies should follow.

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