Very Fast Drug Application to Dissociated Cells and Membrane Patches

2019 ◽  
pp. 73-79
Author(s):  
J. Clements
Keyword(s):  
Drug Application ◽  
Dissociated Cells

Influence of Certain Drugs on the Adhesiveness of Human, Rat, and Rabbit Blood Platelets in Vitro

1965 ◽  
Vol 13 (02) ◽  
pp. 428-438 ◽  
Author(s):  
K Reber ◽  
A Studer
Keyword(s):  
Sodium Citrate ◽  
Blood Platelets ◽  
Drug Application ◽  
Normal Range ◽  
Blood Samples ◽  
Serotonin Antagonist ◽  
Thrombocyte Count ◽  
Particle Count ◽  
Rabbit Blood

SummaryThis is a comparative study of the methods described by H. P. Wright and O’Brien for determining the adhesiveness of thrombocytes. An attempt is made to characterize and statistically correlate both techniques. With the aid of a Coulter Counter for thrombocyte counts, a normal range is presented for human, rat, and rabbit blood. Anticoagulants used are sodium citrate and Heparin.The influence of Cocaine and the Serotonin antagonist Ro 3-0837 was studied on these same substrates, to determine a pharmacological interference with results of either Wright’s test or O’Brien’s. Both drugs are found to induce a statistically significant increase in the “thrombocyte count” as compared to the corresponding controls. These effects are not real but to be attributed to an increase in particle count due to thrombocyte fragmentation as a consequence of drug application. There is no evidence for the claim that these drugs decrease the adhesiveness of thrombocytes.Numerical results of both tests often show a high and statistically significant correlation, especially following the addition of Ro 3-0837. Such is not true of individual blood samples to which no drug has been added. Evidentally, both tests are not specific for the same characteristic of normal blood platelets. But, when Ro 3-0837 is added, the breakdown of unstable platelets is induced; and the corresponding increase in count of thrombocyte fragments is expressed by both tests in the same fashion.

scholarly journals Clinical Presentation and Management of a Dinutuximab Beta Extravasation in a Patient with Neuroblastoma

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 91
Author(s):  
Michael Launspach ◽  
Marita Seif ◽  
Theresa M. Thole ◽  
Patrick Jesse ◽  
Joachim Schulz ◽  
...  
Keyword(s):  
High Risk ◽  
Neuroblastoma Cells ◽  
Drug Application ◽  
Immunocompromised Host ◽  
Laboratory Diagnostics ◽  
Chemotherapy Drugs ◽  
Reactive Protein ◽  
Intravenous Antibiotics ◽  
Inflammatory Toxicity ◽  
Bacterial Superinfection

Extravasation can present serious accidental complication of intravenous drug application. While monoclonal antibodies do not show the necrotic potential of cytotoxic chemotherapy drugs, considerable inflammatory toxicity can occur, necessitating standardized operating procedures for the management of their extravasation. Here, we report the clinical course and management of dinutuximab beta extravasation in a 3-year-old child. Dinutuximab beta is a chimeric monoclonal antibody targeting the GD2 disialoganglioside on the surface of neuroblastoma cells that has in recent years gained significant importance in the treatment of high-risk neuroblastoma, now contributing to both first- and second-line therapy protocols. The dinutuximab beta extravasation reported here occurred when the patient received the antibody cycle as a continuous infusion over a 10-day period after haploidentical stem cell transplantation for relapsed high-risk neuroblastoma. The extravasated dinutuximab beta caused local pain, swelling, and hyperemia accompanied by fever and an overall deterioration in the general condition. Laboratory diagnostics demonstrated an increase in C-reactive protein level and total white blood cell count. Clinical complication management consisted of intravenous fluid therapy, local dabbing with dimethyl sulfoxide (DMSO), analgesia with dipyrone, as well as application of intravenous antibiotics to prevent bacterial superinfection in the severely immunocompromised host. The patient considerably improved after six days with this treatment regimen and fully recovered by day 20.

scholarly journals MYL6B drives the capabilities of proliferation, invasion, and migration in rectal adenocarcinoma through the EMT process

2020 ◽  
Vol 15 (1) ◽  
pp. 522-531
Author(s):  
Jin-Liang Li ◽  
Zai-Qiu Wang ◽  
Xiao-Li Sun
Keyword(s):  
Western Blot ◽  
Cell Apoptosis ◽  
Rectal Adenocarcinoma ◽  
Drug Application ◽  
Biological Significance ◽  
Expression Level ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Promoting Effect

AbstractObjectiveThis study was designed to explore the biological significance of myosin light chain 6B (MYL6B) in rectal adenocarcinoma.MethodsProfiles on the Oncomine dataset, GEPIA website, and UALCAN-TCGA database were searched to assess the MYL6B expression level in rectal adenocarcinoma tissues and normal tissues. After MYL6B knockdown using siRNA strategy, cell counting kit-8 (CCK-8) and transwell assays were conducted to measure cell proliferation, migration and invasion, respectively. Flow cytometry analysis was conducted to assess cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot were performed to detect the expression level of mRNAs and proteins.ResultsThe data showed that overexpression of MYL6B was observed in rectal adenocarcinoma tissues and correlated with a poor prognosis of patients. Functional in vitro experiments revealed that MYL6B knockdown could inhibit proliferation, migration, and invasion of rectal adenocarcinoma cells, while promote cell apoptosis. Moreover, western blot analysis suggested that increased expression of E-cadherin and decreased expression of N-cadherin and Vimentin were induced by si-MYL6B.ConclusionIn summary, this study elaborated on the promoting effect of MYL6B in rectal adenocarcinoma progression, thus providing novel insight for strategies of clinical diagnosis and drug application in the future clinical study.

Subcellular Localization and Complements of GABAA and GABAC Receptors on Bullfrog Retinal Bipolar Cells

2000 ◽  
Vol 84 (2) ◽  
pp. 666-676 ◽  
Author(s):  
Jiu-Lin Du ◽  
Xiong-Li Yang
Keyword(s):  
Subcellular Localization ◽  
Receptor Antagonist ◽  
Gaba Receptor ◽  
Drug Application ◽  
Bipolar Cells ◽  
Visual Signals ◽  
Receptor Subtypes ◽  
Inner Retina ◽  
Axon Terminals ◽  
Retinal Bipolar Cells

γ-Aminobutyric acid (GABA) receptors on retinal bipolar cells (BCs) are highly relevant to spatial and temporal integration of visual signals in the outer and inner retina. In the present work, subcellular localization and complements of GABAA and GABACreceptors on BCs were investigated by whole cell recordings and local drug application via multi-barreled puff pipettes in the bullfrog retinal slice preparation. Four types of the BCs (types 1–4) were identified morphologically by injection of Lucifer yellow. According to the ramification levels of the axon terminals and the responses of these cells to glutamate (or kainate) applied at their dendrites, types 1 and 2 of BCs were supposed to be off type, whereas types 3 and 4 of BCs might be on type. Bicuculline (BIC), a GABAA receptor antagonist, and imidazole-4-acetic acid (I4AA), a GABAC receptor antagonist, were used to distinguish GABA receptor-mediated responses. In all BCs tested, not only the axon terminals but also the dendrites showed high GABA sensitivity mediated by both GABAA and GABACreceptors. Subcellular localization and complements of GABAA and GABAC receptors at the dendrites and axon terminals were highly related to the dichotomy of offand on BCs. In the case of off BCs, GABAA receptors were rather evenly distributed at the dendrites and axon terminals, but GABAC receptors were predominantly expressed at the axon terminals. Moreover, the relative contribution of GABAC receptors to the axon terminals was prevalent over that of GABAA receptors, while the situation was reversed at the dendrites. In the case of on BCs, GABAA and GABAC receptors both preferred to be expressed at the axon terminals; relative contributions of these two GABA receptor subtypes to both the sites were comparable, while GABAC receptors were much less expressed than GABAA receptors. GABAA, but not GABAC receptors, were expressed clusteringly at axons of a population of BCs. In a minority of BCs, I4AA suppressed the GABAC responses at the dendrites, but not at the axon terminal, implying that the GABAC receptors at these two sites may be heterogeneous. Taken together, these results suggest that GABAA and GABAC receptors may play different roles in the outer and inner retina and the differential complements of the two receptors on off and on BCs may be closely related to physiological functions of these cells.

PLATELET ACTIVATION BY HUMAN CANCER CELLS GROWN “IN VITRO” OR DISSOCIATED FROM TUMOUR TISSUES

1987 ◽  
Author(s):  
G Grignani ◽  
L Pacchiarini ◽  
M Zucchella ◽  
L Dezza ◽  
S C Rizzo
Keyword(s):  
Platelet Aggregation ◽  
Platelet Activation ◽  
Human Cancer ◽  
Iodoacetic Acid ◽  
Tumour Cells ◽  
Human Cancer Cells ◽  
Human Tumour Cells ◽  
Dissociated Cells ◽  
Lymphoblastic Cells

The mechanisms of platelet activation by human tumour cells grown “in vitro” or freshly dissociated from tumour tissues have been investigated.MoCCL human T-lymphoblastic cells cultured “in vitro” induced platelet aggregation through the production of ADP, as evidenced by inhibition of the effect by apyrase. The maximum of ADP production by tumour cells was reached after 1 hour and was 225 p moles/106 cells.On the contrary, platelet aggregation induced by 5637 human bladder carcinoma cells was not inhibited by apyrase, but was abolished by hirudin, indicating the important role of thrombin in this effect.Tumour cells dissociated from 3 breast carcinomas showed a very high platelet aggregating activity, which was not inhibited by hirudin or apyrase, but was abolished by iodoacetic acid, suggesting a role for a cystein-protease in platelet activation.These results confirm that platelets can be activated by tumour cells through different mechanisms; they also suggest that the methods employed to obtain the tumour cells can influence the results, probably because of the different cell populations which are present in the dissociated tumour tissues.Informations obtained with freshly dissociated cells are interesting, because this method has been used seldom so far and because it provides a more physiological approach to the study of the interactions of tumours and platelets.

scholarly journals In Vitro Systematic Drug Testing Reveals Carboplatin, Paclitaxel, and Alpelisib as a Potential Novel Combination Treatment for Adult Granulosa Cell Tumors

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 368
Author(s):  
Joline Roze ◽  
Elena Sendino Garví ◽  
Ellen Stelloo ◽  
Christina Stangl ◽  
Ferdinando Sereno ◽  
...  
Keyword(s):  
Granulosa Cell ◽  
Cell Lines ◽  
Combination Treatment ◽  
Drug Testing ◽  
Drug Application ◽  
Hormonal Treatment ◽  
Patient Specific ◽  
Granulosa Cell Tumors ◽  
Potential Synergy

Adult granulosa cell tumors (AGCTs) arise from the estrogen-producing granulosa cells. Treatment of recurrence remains a clinical challenge, as systemic anti-hormonal treatment or chemotherapy is only effective in selected patients. We established a method to rapidly screen for drug responses in vitro using direct patient-derived cell lines in order to optimize treatment selection. The response to 11 monotherapies and 12 combination therapies, including chemotherapeutic, anti-hormonal, and targeted agents, were tested in 12 AGCT-patient-derived cell lines and an AGCT cell line (KGN). Drug screens were performed within 3 weeks after tissue collection by measurement of cell viability 72 h after drug application. The potential synergy of drug combinations was assessed. The human maximum drug plasma concentration (Cmax) and steady state (Css) thresholds obtained from available phase I/II clinical trials were used to predict potential toxicity in patients. Patient-derived AGCT cell lines demonstrated resistance to all monotherapies. All cell lines showed synergistic growth inhibition by combination treatment with carboplatin, paclitaxel, and alpelisib at a concentration needed to obtain 50% cell death (IC50) that are below the maximum achievable concentration in patients (IC50 < Cmax). We show that AGCT cell lines can be rapidly established and used for patient-specific in vitro drug testing, which may guide treatment decisions. Combination treatment with carboplatin, paclitaxel, and alpelisib was consistently effective in AGCT cell lines and should be further studied as a potential effective combination for AGCT treatment in patients.

scholarly journals Whole-Body Regeneration in Sponges: Diversity, Fine Mechanisms, and Future Prospects

Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 506
Author(s):  
Alexander Ereskovsky ◽  
Ilya E. Borisenko ◽  
Fyodor V. Bolshakov ◽  
Andrey I. Lavrov
Keyword(s):  
Single Species ◽  
Whole Body ◽  
Phylogenetic Position ◽  
Main Body ◽  
Regenerative Processes ◽  
Cellular Mechanisms ◽  
Different Types ◽  
Dissociated Cells ◽  
Shed Light ◽  
Regeneration Processes

While virtually all animals show certain abilities for regeneration after an injury, these abilities vary greatly among metazoans. Porifera (Sponges) is basal metazoans characterized by a wide variety of different regenerative processes, including whole-body regeneration (WBR). Considering phylogenetic position and unique body organization, sponges are highly promising models, as they can shed light on the origin and early evolution of regeneration in general and WBR in particular. The present review summarizes available data on the morphogenetic and cellular mechanisms accompanying different types of WBR in sponges. Sponges show a high diversity of WBR, which principally could be divided into (1) WBR from a body fragment and (2) WBR by aggregation of dissociated cells. Sponges belonging to different phylogenetic clades and even to different species and/or differing in the anatomical structure undergo different morphogeneses after similar operations. A common characteristic feature of WBR in sponges is the instability of the main body axis: a change of the organism polarity is described during all types of WBR. The cellular mechanisms of WBR are different across sponge classes, while cell dedifferentiations and transdifferentiations are involved in regeneration processes in all sponges. Data considering molecular regulation of WBR in sponges are extremely scarce. However, the possibility to achieve various types of WBR ensured by common morphogenetic and cellular basis in a single species makes sponges highly accessible for future comprehensive physiological, biochemical, and molecular studies of regeneration processes.

scholarly journals Effects of different combined regimens of cisplatin, metformin, and quercetin on nasopharyngeal carcinoma cells and subcutaneous xenografts

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhongwei Chen ◽  
Zhen Zeng ◽  
Shanshan Zhu ◽  
Ying Zeng ◽  
Qihuang Lin ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Nude Mice ◽  
Drug Combination ◽  
Drug Application ◽  
Inhibitory Effects ◽  
Single Drug ◽  
Combined Application ◽  
Subcutaneous Xenograft ◽  
Recurrent Nasopharyngeal Carcinoma ◽  
Combination Regimens

AbstractCisplatin, metformin, and quercetin are all reliable anticancer drugs. However, it is unclear how effective their different combination regimens are on the growth of nasopharyngeal carcinoma cell line Sune-1 and subcutaneous xenograft in nude mice. This study evaluated the effects of single-drug, two-drug, and three-drug simultaneous or sequential combined application of these drugs on the growth of Sune-1 cells and subcutaneous xenograft tumors in nude mice. The results showed that the different combination regimens of cisplatin, metformin and quercetin all had significant inhibitory effects on the proliferation of Sune-1 cells and the growth of subcutaneous xenografts in nude mice (P < 0.01), and the inhibition rate of the three drugs simultaneous combined application was significant Higher than the two-drug combination or single-drug application (P < 0.05), the contribution level of each drug in the three-drug combination application from high to low were cisplatin > metformin > quercetin. In summary, our results indicate that the simultaneous combination of cisplatin, metformin, and quercetin may synergistically inhibit the growth of Sune-1 cells and subcutaneous xenografts in nude mice through their different anticancer mechanisms, which may be clinically refractory and provide reference for chemotherapy of patients with recurrent nasopharyngeal carcinoma.

scholarly journals Comparison of Antimicrobial Treatment Incidence Quantification Based on Detailed Field Data on Animal Level with the Standardized Methodology of the European Medicines Agency in Veal Calves, Switzerland, 2016–2018

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 832
Author(s):  
Jens Becker ◽  
Mireille Meylan
Keyword(s):  
Field Data ◽  
Drug Application ◽  
Drug Level ◽  
Antimicrobial Treatment ◽  
European Medicines Agency ◽  
Veterinary Medicines ◽  
Defined Daily Doses ◽  
Class Level ◽  
Precise Quantification ◽  
Good Agreement

Precise quantification of antimicrobial treatment incidence (TI) is crucial for benchmarking. Two widespread methods for treatment incidence quantification were compared for agreement. Field data were obtained from 38 veal farms from 2016 to 2018 (1905 calves, 1864 treatments). Calculation of TIswiss for calves was based on detailed treatment records using pharmacokinetic values from the Swiss Veterinary Medicines Compendium. The method published by the European Medicines Agency was used to calculate TI in defined daily doses (TIDDD). For each calf and treatment, TIswiss and TIDDD were calculated on level of the antimicrobial class, drug, application route, and farm. The quotient (Q) of TIswiss and TIDDD was calculated. Divergence in results between the two methods of ≤25% was arbitrarily set as good agreement. The agreement between TIswiss and TIDDD was mostly good. On class level, good agreement was observed for treatments representing 71.5% of the TIDDD, and 74.5% of the total TIDDD on drug level. Poor agreement was mainly observed for tylosin and sulfadimidine. The agreement was better for parenteral than for oral treatments (81.6% vs. 72.3%). For practically orientated calculation on farm level, good agreement was observed (77.5% of the TIDDD). The TIDDD method showed mostly good agreement, especially for parenteral treatments.

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