scholarly journals Study of Binding Kinetics and Specificity of 99mTc-SSS-Complex and 99mTc-HMPAO to Blood Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
S. Auletta ◽  
V. Iodice ◽  
F. Galli ◽  
N. Lepareur ◽  
A. Devillers ◽  
...  

Nuclear medicine offers several techniques and procedures to image infection, but radiolabelled autologous white blood cells (WBCs) are still the gold standard. These cells are usually labelled with 111In or 99mTc bound to a hydrophobic chelating agent that allows these isotopes to pass through the plasma membrane and enter in the cytoplasm. The most common compound in Europe is HMPAO that efficiently chelates 99mTc. However, up to 20–40% of the complex is released from the cells in the first few hours. The aim of this study was to radiolabel a new compound, (S3CPh)2 (S2CPh)-complex (SSS-complex) with 99mTc and compare its binding kinetics and specificity for WBC with HMPAO. The SSS-complex was labelled with 99mTc and analysed by iTLC and RP-HPLC. In vitro quality controls included a stability assay in serum and saline. Results showed a labelling efficiency of 95 ± 1.2% and 98 ± 1.4% for 99mTc-SSS-complex and 99mTc-HMPAO, respectively (p=ns). 99mTc-SSS-complex was stable in serum and in saline up to 24 h (94 ± 0.1%). Cell labelling experiments showed a higher incorporation of 99mTc-SSS-complex than 99mTc-HMPAO by granulocytes (62.6 ± 17.8% vs 40.5 ± 15%, p=0.05), lymphocytes (59.9 ± 22.2% vs 29.4 ± 13.5%; p=0.03), and platelets (44.4 ± 24% vs 20.5 ± 10.7%; p=ns), but the release of radiopharmaceutical from granulocytes at 1 h was lower for HMPAO than for SSS-complex (10.3 ± 1.9% vs 21.3 ± 1.8%; p=0.001). In conclusion, 99mTc-SSS-complex, although showing high labelling efficiency, radiochemical purity, and stability, is not a valid alternative to 99mTc-HMPAO, for example, in vivo white blood cells labelling because of high lymphocyte and platelet uptake and rapid washout from granulocytes.

1998 ◽  
Vol 95 ◽  
pp. 41
Author(s):  
B. Marczynski ◽  
M. Peel ◽  
P. Rozynek ◽  
J. Elliehausen ◽  
M. Korn ◽  
...  

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 53-62 ◽  
Author(s):  
H Loos ◽  
D Roos ◽  
R Weening ◽  
J Houwerzijl

A virtually complete absence of glutathione reductase activity was found in the erythrocytes of all three children (one male, two females) from a consanguineous marriage. Intermediate values were found in the erythrocytes of both parents. The enzyme activity could not be restored either by addition of FAD in vitro or by administration of riboflavin in vivo. The amount of reduced glutathione in the erythrocytes was normal in each case. Severely diminished glutathione stability during incubation with acetylphenylhydrazine was observed in the erythrocytes of the siblings, as well as intermediate stability in the parents' red cells. Clinically, this deficiency was manifested by hemolytic crises after eating fava beans in the eldest daughter (patient), and possibly by cataracts in her own and in her brother's eyes. Very low activities of glutathione reductase were also found in the leukocytes of this family: 13%-15% of normal values for the children and 64%-66% for the parents. Moreover, the same deficiency was found in the purified white blood cells of the propositus: 8% of normal values in the polymorphonuclear (PMN) cells, 4% in the lymphocytes, and 15% in the monocytes, together with 11% in the platelets. Finally, we found an abnormal oxygen consumption of the propositus' PMNs after phagocytosis of zymosan particles, suggesting that the glutathione reductase reaction was involved in the bactericidal capacity of these cells.


2021 ◽  
Vol 12 ◽  
Author(s):  
Gregory Barshtein ◽  
Ivana Pajic-Lijakovic ◽  
Alexander Gural

Red blood cells (RBCs) deformability refers to the cells’ ability to adapt their shape to the dynamically changing flow conditions so as to minimize their resistance to flow. The high red cell deformability enables it to pass through small blood vessels and significantly determines erythrocyte survival. Under normal physiological states, the RBCs are attuned to allow for adequate blood flow. However, rigid erythrocytes can disrupt the perfusion of peripheral tissues and directly block microvessels. Therefore, RBC deformability has been recognized as a sensitive indicator of RBC functionality. The loss of deformability, which a change in the cell shape can cause, modification of cell membrane or a shift in cytosol composition, can occur due to various pathological conditions or as a part of normal RBC aging (in vitro or in vivo). However, despite extensive research, we still do not fully understand the processes leading to increased cell rigidity under cold storage conditions in a blood bank (in vitro aging), In the present review, we discuss publications that examined the effect of RBCs’ cold storage on their deformability and the biological mechanisms governing this change. We first discuss the change in the deformability of cells during their cold storage. After that, we consider storage-related alterations in RBCs features, which can lead to impaired cell deformation. Finally, we attempt to trace a causal relationship between the observed phenomena and offer recommendations for improving the functionality of stored cells.


Perfusion ◽  
1994 ◽  
Vol 9 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Per Bergman ◽  
Ali Belboul ◽  
Lars Göran Friberg ◽  
Najib Al-Khaja ◽  
Gösta Mellgren ◽  
...  

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% ± 9, 72% ± 2 and 76% ± 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 ± 1.5, 32.6 ± 2.2 and 40.3 ± 8.3 x 102%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 ± 1.5, 9.7 ± 1.2 and 13.9 ± 2.1 x 106/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% ± 0.3, 23% ± 0.2 and 14% ± 0.1 at 24,48 and 72 hours respectively (p < 0.001). This study showed a serious loss in white cell rheology during PPMO, which may contribute to the plugging effect of the microvessels in clinical use and may explain the organ dysfunction seen during ECMO on the basis of inadequate tissue oxygenation and nutrition due to areas of reduced perfusion, which results in increased frequency of morbidity.


2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Diones Caeran Bueno ◽  
Daiane Francine Meinerz ◽  
Josiane Allebrandt ◽  
Emily Pansera Waczuk ◽  
Danúbia Bonfanti dos Santos ◽  
...  

Organochalcogens, particularly ebselen, have been used in experimental and clinical trials with borderline efficacy. (PhSe)2and (PhTe)2are the simplest of the diaryl dichalcogenides and share with ebselen pharmacological properties. In view of the concerns with the use of mammals in studies and the great number of new organochalcogens with potential pharmacological properties that have been synthesized, it becomes important to develop screening protocols to select compounds that are worth to be testedin vivo. This study investigated the possible use of isolated human white cells as a preliminary model to test organochalcogen toxicity. Human leucocytes were exposed to 5–50 μM of ebselen, (PhSe)2, or (PhTe)2. All compounds were cytotoxic (Trypan’s Blue exclusion) at the highest concentration tested, and Ebselen was the most toxic. Ebselen and (PhSe)2were genotoxic (Comet Assay) only at 50 μM, and (PhTe)2at 5–50 μM. Here, the acute cytotoxicity did not correspond within vivotoxicity of the compounds. But the genotoxicity was in the same order of thein vivotoxicity to mice. These results indicate thatin vitrogenotoxicity in white blood cells should be considered as an early step in the investigation of potential toxicity of organochalcogens.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2273-2273
Author(s):  
Nathalie W.D. Jansen ◽  
Goris Roosendaal ◽  
Marion Wenting ◽  
Herman A.W. Hazewinkel ◽  
Johannes W.J. Bijlsma ◽  
...  

Abstract Purpose Joint bleeds lead to joint destruction. In vitro exposure of human and canine cartilage to blood results in long lasting severe adverse changes in cartilage. An in vivo joint haemorrhage in the canine knee joint demonstrates similar adverse effects although less outspoken and long-lasting. We investigated the clearance rate of blood from canine knee joints as a possible explanation for this discrepancy. Methods Blood was injected into the knee joint of Beagle dogs, either 48h, 24h or 15m before termination. The amount of red and white blood cells present in the joint cavity was determined. Chondrocyte activity and cartilage matrix integrity as well as cartilage destructive activity of synovial tissue were determined biochemically. Additionally, synovial tissue was analyzed by use of histochemistry. Results Fifteen minutes after the injection of autologous blood, the red blood cell count was 5,7*1012/L, comparable to the amount present in whole blood, and gradually decreased (1,6*1012/L at 24 hours) to 0,2*1012/L within 48 hours (less than 5%). The amount of white blood cells increased in the first 24 hours, and was still increased after 48 hours, although less than after 24 hours. The proteoglycan synthesis rate and -release were adversely affected already within 24 hours (−22% and +24% respectively), and these effects were more severe 48 hours post-injection (−34% and +53% resp.). Synovial tissue culture supernatants demonstrate cartilage destructive properties as expressed by an increased release, a decreased synthesis rate, and decreased content of cartilage proteoglycans; increasing with time after the experimental haemorrhage (+207%/+247%; −58%/−62%; −8%/−28% respectively, for 24/48 hours). Evaluation of the synovial tissue revealed at 15 minutes post-injection countless numbers of intact RBC that were almost completely disappared after 48 hours, withonly limited recruitment of macrophages and iron deposition. Conclusions Blood is cleared very rapidly from the canine knee joint, but in that short time span already has adverse effects on both cartilage and synovial tissue. This rapid clearance can play a role in the discrepancy between long-term in vitro and in vivo effects of blood-induced joint damage since more than 10% v/v blood for 48 hours is needed induced to long-term adverse effects in vitro. Irrespectively, blood has devastating effects on articular cartilage very rapidly, and in this respect it is important to prevent (traumatic) joint haemorrhages and if they occur, to treat them properly.


2009 ◽  
Vol 59 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Sarbani Ray ◽  
Partha Roy ◽  
Supratim Ray

Sterodin®, a novel immunostimulating drug: Some toxicological and pharmacological evaluations in vivo, and drug-lipid interaction studies in vitro Sterodin® is a novel non-specific immunostimulating drug produced by a combination of bile lipids and bacterial metabolites. In the present study, we investigated some of its (i) toxicological and (ii) pharmacological properties in vivo, and (iii) drug-lipid interaction (lipid peroxidation) in vitro. We also evaluated the possible (iv) Sterodin®-induced lipid peroxidation as well as the effect of ascorbic acid on this peroxidation. We found LD50 of Sterodin® to be 31.50 mL kg-1 body mass. In male albino mice, Sterodin® increased the total white blood cells and neutrophils count by 59 and 26%, respectively, on the 6th day, compared to day 0 after injection and stimulated phagocytic activity in vivo. We used goat liver as lipid source in drug-lipid interaction studies in vitro. Our experiments show that Sterodin® induces lipid peroxidation, which was prevented by ascorbic acid.


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