Very Rapid Clearance after a Joint Bleed Knee Can Not Prevent Adverse Effects on Cartilage and Synovial Tissue: A Canine in Vivo Study.

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 ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Knee Joint ◽  
Synovial Tissue ◽  
Blood Cells ◽  
White Blood Cells ◽  
Synthesis Rate ◽  
Rapid Clearance

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.

NORMAL GRANULOCYTE INFUSION THERAPY FOR ASPERGILLOSIS IN CHRONIC GRANULOMATOUS DISEASE

PEDIATRICS ◽  
1973 ◽  
Vol 51 (2) ◽  
pp. 230-233
Author(s):  
Andrew A. Raubitschek ◽  
Alan S. Levin ◽  
Daniel P. Stites ◽  
Edward B. Shaw ◽  
H. Hugh Fudenberg
Keyword(s):  
Adverse Effects ◽  
Chronic Granulomatous Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Infusion Therapy ◽  
Granulomatous Disease ◽  
Transient Improvement ◽  
Life Threatening ◽  
Granulocyte Function

An 8-year-old boy with chronic granulomatous disease (CGD) was admitted in moribund condition with aspergillus pneumonia. Because of the gravity of the situation, normal granulocyte infusions were used as adjuncts to the more conventional antimicrobial therapy. White blood cells, derived from a total of 58 units of whole blood obtained by leukophoresis of the father, were given in two separate doses. The first dose, totaling 2.8 x 1010 granulocytes, was coincident with significant improvement, and the second, totaling 3.0 x 1010 granulocytes, was coincident with the onset of clinical improvement and interim recovery. Transient improvement in in vitro granulocyte function was noted in cells taken from the patient's blood immediately after infusion. No adverse effects of the infusions were noted in either the patient or the donor. Although it is impossible to divorce the therapeutic effect of the granulocyte infusions from the more conventional therapy, we conclude that normal granulocyte infusions can be considered a valid adjunct in children with CGD who are suffering from a life-threatening infection.

Hepatocytes Ingest Longterm Refrigerated Platelets: A Novel Platelet Clearance Mechanism.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1523-1523 ◽  
Author(s):  
Viktoria Rumjantseva ◽  
Emma C. Josefsson ◽  
Hans Wandall ◽  
John H. Hartwig ◽  
Thomas P. Stossel ◽  
...  
Keyword(s):  
Cold Storage ◽  
Fluorescent Microscopy ◽  
Hepatic Clearance ◽  
Human Platelets ◽  
Lectin Domain ◽  
Clearance Mechanism ◽  
Rapid Clearance

Abstract We previously reported that the lectin domain of αMβ2 receptors on hepatic macrophages mediates rapid clearance of washed murine platelets transfused after refrigeration for 2 hours, recognizing exposed βN-acetylglucosamine (βGlcNAc) residues of N-linked glycans on clustered platelet GPIbα molecules and that the same receptors elicit phagocytosis of refrigerated human platelets human macrophages in vitro. A platelet-associated galactosyltransferase catalyzes the covering of βGlcNAc residues with galactose in the presence of UDP-galactose, thereby blocking clearance of cold mouse platelets in vivo and phagocytosis of human platelets in vitro. These intriguing findings contradicted earlier evidence that refrigeration of human platelets procured for transfusion only promotes their rapid clearance after prolonged (>8h) incubation and also are inconsistent with the well-known recognition system for exposed galactose residues through asialoglycoprotein (ASGP) receptors. Reconciling these contradictions, we report that the absence of plasma during storage accounts for the differences in time of exposure to cold to promote clearance and that mouse platelets cold-stored in plasma also only clear rapidly after long-term (48h) storage. We also found that hepatic clearance of long-term cold-stored (LTCS) mouse platelets occurs in hepatocytes. Streptavidin-POD staining revealed abundant LTCS biotinylated platelets in hepatocyte phagosomes. Furthermore, cells of the hepatocyte HepG2 line avidly ingest fluorescently-labeled LTCS human platelets (7-fold above the baseline of room-temperature-stored platelets), as evidenced by flow cytometry, fluorescent microscopy and by time-laps video microscopy. Long-term cold storage increases by ~1.7-fold platelet binding of the galactose-specific lectin RCA I, implying that with long-term cold storage, exposed galactose residues cluster sufficiently to induce recognition by hepatocyte ASGPR receptors. The results define a new clearance mechanism, representing the first example of blood cell removal by a non-myeloid cell. Since we find that human platelets also express a cell surface sialotransferase that adds sialic acid to galactose residues, we suggest that a combination of sialylation and glactosylation, achievable by addition of sugar substrates alone, might accommodate long-term cold storage of platelets for transfusion.

Genotoxic effects in human white blood cells following styrene (in vivo) and styrene oxide (in vitro) exposure

1998 ◽  
Vol 95 ◽  
pp. 41
Author(s):  
B. Marczynski ◽  
M. Peel ◽  
P. Rozynek ◽  
J. Elliehausen ◽  
M. Korn ◽  
...  
Keyword(s):  
Blood Cells ◽  
Styrene Oxide ◽  
White Blood Cells ◽  
Genotoxic Effects ◽  
In Vitro Exposure ◽  
Human White Blood Cells

In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34+ cord blood cells

2000 ◽  
Vol 28 (12) ◽  
pp. 1470-1480 ◽  
Author(s):  
Ladan Kobari ◽  
Françoise Pflumio ◽  
Marie-Catherine Giarratana ◽  
Xiaxin Li ◽  
Monique Titeux ◽  
...  
Keyword(s):  
Cord Blood ◽  
Blood Cells ◽  
Ex Vivo ◽  
Human Cd34 ◽  
Cord Blood Cells

scholarly journals Familial deficiency of glutathione reductase in human blood cells

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 53-62 ◽  
Author(s):  
H Loos ◽  
D Roos ◽  
R Weening ◽  
J Houwerzijl
Keyword(s):  
Glutathione Reductase ◽  
Blood Cells ◽  
Normal Values ◽  
Reductase Activity ◽  
White Blood Cells ◽  
Human Blood Cells ◽  
Glutathione Reductase Activity ◽  
Fava Beans

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.

In vitro And In vivo Evidences for the long-term multilineage (Myeloid, b, nk & t) Reconstitution capacity of Ex vivo Expanded human CD34+ cord blood cells

2000 ◽  
Vol 28 (7) ◽  
pp. 47-48
Author(s):  
L. Douay ◽  
L. Kobari ◽  
F. Pflumio ◽  
M.C. Giarratana ◽  
X. Li ◽  
...  
Keyword(s):  
Cord Blood ◽  
Blood Cells ◽  
Ex Vivo ◽  
Human Cd34 ◽  
Cord Blood Cells

scholarly journals Cytotoxicity and Genotoxicity Evaluation of Organochalcogens in Human Leucocytes: A Comparative Study between Ebselen, Diphenyl Diselenide, and Diphenyl Ditelluride

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Diones Caeran Bueno ◽  
Daiane Francine Meinerz ◽  
Josiane Allebrandt ◽  
Emily Pansera Waczuk ◽  
Danúbia Bonfanti dos Santos ◽  
...  
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Pharmacological Properties ◽  
Potential Toxicity ◽  
Early Step ◽  
Preliminary Model ◽  
Diphenyl Ditelluride ◽  
Acute Cytotoxicity

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.

scholarly journals Sterodin®, a novel immunostimulating drug: Some toxicological and pharmacological evaluations in vivo, and drug-lipid interaction studies in vitro

2009 ◽  
Vol 59 (3) ◽  
pp. 325-334 ◽  
Author(s):  
Sarbani Ray ◽  
Partha Roy ◽  
Supratim Ray
Keyword(s):  
Lipid Peroxidation ◽  
Ascorbic Acid ◽  
Blood Cells ◽  
White Blood Cells ◽  
Pharmacological Properties ◽  
Lipid Source ◽  
Interaction Studies ◽  
Lipid Interaction

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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