scholarly journals Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1054
Author(s):  
Ilya Yakavets ◽  
Igor Yankovsky ◽  
Tatyana Zorina ◽  
Mikhail Belevtsev ◽  
Lina Bezdetnaya ◽  
...  

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

2021 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Inès Ait Belkacem ◽  
Isabelle Arnoux ◽  
Pierre-Emmanuel Morange ◽  
Fabrice Malergue

Aim: A new one-step flow cytometry procedure has been recently demonstrated for identifying subjects with infections, but only for fresh whole blood samples. The goal of this study was to assess its applicability on frozen samples, by proposing a new method to perform the sample freezing directly and easily. Methods: Fresh blood was tested, then frozen either directly or with dimethylsulfoxide and serum. Common markers of white blood cells as well as infection-related biomarkers were tested. Results: All percentages of leucocyte subsets and levels of infection-related biomarkers were significantly correlated between frozen and fresh samples. Conclusion: The direct freezing method enables an accurate assessment of common cellular sub-populations and of levels of important infectious biomarkers via flow cytometry.


2005 ◽  
Vol 48 (spe2) ◽  
pp. 13-27 ◽  
Author(s):  
Mario Bernardo-Filho ◽  
Sebastião David Santos-Filho ◽  
Egberto Gaspar de Moura ◽  
Adalgisa Ieda Maiworm ◽  
Margarida Maria de Camões Orlando ◽  
...  

Clinical images are worthwhile in Health Sciences and their analysis and correct interpretation aid the professionals,such as physicians, physiotherapists and occupational therapists, to make decisions and take subsequent therapeutic and/or rehabilitation measures. Other factors, besides the state of the disease, may interfere and affect the bioavailability of the radiopharmaceuticals (radiobiocomplexes) and the quality of the SPECT and PET images. Furthermore, the labeling of some of these radiobiocomplexes, such as plasma proteins, white blood cells and red blood cells, with 99mT, can also be modified. These factors include drugs (synthetic and natural) and dietary conditions, as well as some medical procedures (invasive or non-invasive), such as radiation therapy, surgical procedures, prostheses, cardioversion, intubation, chemoperfusion, external massage, immunotherapy, blood transfusion and hemodialysis. In conclusion, the knowledge about these factors capable of interfering with the bioavailability of the radiobiocomplexes is worthwhile for secure diagnosis. Moreover, the development of biological models to study these phenomena is highly relevant and desirable.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4741-4741
Author(s):  
Xiaoxian Zhao ◽  
Wouter Korver ◽  
Nichole Prescott ◽  
Arie Abo ◽  
Eric Hsi

Abstract Introduction: Expressed on T, B, NK cells and neutrophils, NTB-A belongs to the signaling lymphocytic activation molecule (SLAM) family of immune receptors. It was reported recently that cross-linking of NTB-A induces T cell activation and Ly108 (the presumed mouse orthologue of NTB-A) controls the production of reactive oxygen species in neutrophils. To date, little is known about its expression at the protein level in normal tissues, or in hematologic malignancies. Methods: We have generated monoclonal antibodies (mAbs) to NTB-A and used tissue microarrays (TMAs) to screen normal tissues and lymphomas. Western blotting and flow cytometry were used for confirmation of selected entities. Complement dependent cytotoxicity (CDC) assays were performed using the CellTiter-Glo Luminescent Cell Viability Assay kit (Promega). Results: NTB-A was not detected in normal tissues including heart, liver, breast, kidney, brain, lung, uterus, small intestine, skin, prostate, pancreas, ovary, bladder, testis and stomach (5/5 negative cases for all above tissues) by IHC. Expression was observed in lymphocytes of normal tonsil and spleen. In lymphomas, we found NTB-A expression in diffuse large B-cell lymphoma (DLBL), follicular lymphoma, small lymphocytic lymphoma (SLL), mantle cell lymphoma and Burkitt lymphoma. Western blotting and flow cytometry of B-cell lymphoma cell lines DOHH2 (DLBL) and Raji (Burkitt) confirmed NTB-A expression in these lines. Myeloma cell lines were negative for expression. Flow cytometry of normal blood cells showed expression of NTB-A in B-cells, T-cells and NK cells (95.5 ± 6.7%, 62.6 ± 29.5% and 72.7 ± 26.5%, respectively) but not in CD66+ granulocytes. Furthermore, CD34+ progenitor cells from bone marrow were negative. Because of the expression in SLL, we focused on chronic lymphocytic leykemia (CLL) cells. All (15/15) patient samples were confirmed positive by flow cytometry. No significant differences in expression levels were observed comparing CLL B-cells vs normal B-cells (n = 10). However, anti-NTB-A antibodies were capable of inducing CDC in white blood cells from CLL patients (n=5) but not in normal white blood cells (n=5), in addition to CDC activity against Raji cells. Preliminary data also suggests that the CDC effect is greater in purified CLL B-cells than purified normal B-cells. Conclusions: These results show that NTB-A is expressed in normal lymphocytes but not in other solid tissues or in CD34+ progenitor cells. B cell malignancies, including Non-Hodgkin lymphoma cells appear to express NTB-A. In particular CLL patient cells express NTB-A, and an anti-NTB-A mouse mAb is capable of inducing CDC, suggesting NTB-A may be a potential immunotherapeutic target. Further studies examining the expression patterns in hematologic malignancies are ongoing.


2016 ◽  
Vol 54 (2) ◽  
pp. 266-270 ◽  
Author(s):  
Silvia Castegnaro ◽  
Patrizia Dragone ◽  
Katia Chieregato ◽  
Alberta Alghisi ◽  
Francesco Rodeghiero ◽  
...  

2017 ◽  
Vol 45 (5) ◽  
Author(s):  
Alicia Martinez-Varea ◽  
Roberto Romero ◽  
Yi Xu ◽  
Derek Miller ◽  
Ahmed I. Ahmed ◽  
...  

AbstractObjectives:1) To characterize the cellular composition of the amniotic fluid of patients diagnosed with clinical chorioamnionitis at term, as a function of the presence or absence of microorganisms determined by cultivation techniques, and 2) to characterize the cytokine production by white blood cells present in the amniotic fluid using flow cytometry-based techniques.Materials and methods:Amniotic fluid samples from 20 women who had the diagnosis of clinical chorioamnionitis at term were analyzed using cultivation techniques (for aerobic and anaerobic bacteria as well as genital Mycoplasmas). Amniotic fluid IL-6 concentrations were determined by an enzyme-linked immunosorbent assay. Amniotic fluid leukocytes were visualized by using hematoxylin and eosin staining and immunofluorescence. Immunophenotyping of surface markers and cytokines was performed in amniotic fluid leukocytes using flow cytometry.Results:1) Neutrophils (CD45+CD15+ cells) were the most common leukocyte subset found in the amniotic fluid, followed by monocytes (CD45+CD14+ cells); other white blood cells (such as lymphocytes and natural killer cells) were scarce in the amniotic fluid; 2) the absolute counts of neutrophils and monocytes were significantly higher in patients with microorganisms found in the amniotic fluid than in those without detectable microorganisms, using cultivation techniques; 3) there was a significant correlation between the absolute counts of neutrophils and monocytes determined by flow cytometry (Spearman’s correlation=0.97; P<0.001); 4) there was a significant correlation between the absolute white blood cell count determined with a hemocytometer chamber and by flow cytometric analysis (Spearman’s correlation=0.88; P<0.001); and 5) the profile of cytokine expression differed between monocytes and neutrophils; while neutrophils predominantly produced TNF-α and MIP-1β, monocytes expressed higher levels of IL-1β and IL-1α.Conclusion:Flow cytometry analysis of the amniotic fluid of patients with intra-amniotic infection and clinical chorioamnionitis at term demonstrated that neutrophils and monocytes are the most common cells participating in the inflammatory process. We have characterized, for the first time, the differential cytokine expression by these cells in this important complication of pregnancy.


2021 ◽  
pp. 25-30
Author(s):  
R. R. Ismagilov ◽  
F. S. Bilalov ◽  
Yu. A. Ahmadullina ◽  
M. N. Sitdikova ◽  
A. Zh. Gilmanov

We studied changes in the parameters of the general (clinical) blood test in dynamics in outpatient patients with an asymptomatic course and a mild degree of severity of COVID-19. The study involved 67 patients. 30 men and 37 women were examined, their average age was 35 years. All the interviewed patients did not take specific antiviral drugs. Clinical manifestations were evaluated at the time of the survey on the 1st and 7th day from the day of receiving a positive PCR result. The parameters of the general (clinical) blood test were determined by flow cytometry in the CBC + 5Diff mode on a Unicel® DxH 800 hematological analyzer (Beckman Coulter, USA) in dynamics on the 1st and 7th days of observation. The features of clinical manifestations in patients with an asymptomatic course and mild severity coincided with the data of other authors. Hematological changes were mainly characterized by changes in the number of white blood cells and their subpopulations. On the 7th day of observation, there was a significant tendency to increase the number of white blood cells, lymphocytes, eosinophils, neutrophils and platelets within the reference intervals.


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