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The pharmacokinetics of iohexol, a new nonionic, water-soluble contrast medium, have been determined after intravenous injection in 20 healthy volunteers, at four different dose levels (125-500 mg I/kg). The apparent volume of distribution was 0.27 1/kg, indicating distribution in the extracellular water. The biologic half-life was 121 minutes, comparable with that of other intravascular contrast media. Iohexol was excreted completely unmetabolized in the urine, with a 100% recovery 24 hours after injection. A comparison of iohexol and chromium-51 (51Cr)-EDTA clearances indicates that iohexol is mainly excreted by glomerular filtration. The 51Cr-EDTA clearance was the same when injected separately and concomitantly with iohexol, indicating that glomerular filtration rate is not affected by iohexol. No dose dependency was observed in the investigated parameters t1/2 alpha, t1/2 beta, Vd, ClT or ClR. Iohexol pharmacokinetics are in correspondence with previously reported data on intravascular contrast media.

Wound chambers implanted subcutaneously in rabbits proved suitable for measurements of leukocyte chemotaxis. Injection of bacterial lipopolysaccharide (LPS) in the chambers the sixth day after implantation was followed by a marked increase of polymorphonuclear leukocytes in the wound chamber fluid, the number of which was dependent on the time after application of LPS. Up to a certain amount of LPS, the concentration of leukocytes in the chamber fluid was dose-dependent. The histopathological appearance of the granulation tissue lining the chamber wall one day after the injection of LPS from Veillonella revealed aggregation of blood cells plugging the lumina of small vessels and many eosinophilic leukocytes.

Endotoxic lipopolysaccharides (LPS) isolated from Fusobacterium are similar to those of Salmonella with respect to chemical composition, O-antigenic specificity and endotoxic activity. Bacteroides LPS are highly atypical with respect to the chemical composition, and their endotoxic activity is low. O-Antigenic specificity is present. B. fragilis LPS is chemotactic for polymorphonuclear leukocytes in vitro and in vivo. The chemotactic activity is brought about by activation of the alternative complement pathway.

Preparations of the polymorphonuclear leukocyte (PMN) chemotactic factor isolated from lipopolysaccharide (LPS)-induced inflammatory exudate in rabbits were immunogenic in guinea pigs. Complete fusion of the precipitation lines produced against anti-CF by LPS-CF (molecular weigth 16,000) and material eluted on Sephadex G-200 columns with molecular weights (MW) of 68,000, 16,000 and 7,000 was found. Also, the chemotactically active material with MW of 68,000 and 7,000 eluted on G-75 columns after fractionation of the fraction of MW 16,000 from the G-200 eluate was antigenically identical to LPS-CF in double diffusion in agar. Normal rabbit serum (NRS) incubated with LPS, LPS-induced wound chamber exudate and NRS alone gave lines of precipitation against the anti-LPS-CF sera identical to that of LPS-CF. The capacity of LPS-CF to attract PMNs was significantly higher than that of LPS, and a peak in the number of PMNs in the exudate of wound chambers implanted in rabbits was found 4 h after the local injection of LPS-CF. When injected intraperitoneally in C5 deficient mice, LPS-CF stimulated a PMN migration which was only slightly below that in C5 normal mice. Antisera to LPS-CF inhibited the chemotactic activity of LPS-CF as well as that of LPS-NRS when the supernatants were tested using the Boyden's technique. Also, preincubation of PMNs with LPS-CF suppressed the migration towards a chemotactic gradient of LPS-CF molecules of these PMNs.

Chambers implanted subcutaneously in C5 normal (C5 N) and C5 deficient (C5 D) mice were used to examine the migration of polymorphonuclear leukocytes (PMNs) into the wound chamber fluid in response to injected Bacteroides fragilis lipopolysaccharide (LPS). The difference in PMN migration was highly significant between the two mouse strains, the C5 D mice showing no initial, but a low, delayed migration. The results from the study indicated that chemotaxis plays a major role in the accumulation of PMNs in the acute inflammatory response. Intraperitoneal endotoxin stimulation also showed a significantly lower total number of leukocytes in the exudate from C5 D mice as well as a delayed migration of cells compared to C5 N mice. No leukotactic mediators were elaborated in C5 D serum or exudate upon incubation with LPS when tested in a modified Boyden chamber. However, endotoxin-induced wound chamber fluid in C5 D mice showed an increasing leukotactic activity at the same time as the acute inflammatory response subsided in C5 N mice. Incubation of B. fragilis LPS in C4 deficient (C4 D) guinea pig serum indicated that the LPS was able to activate complement components to generated split products chemotacic for rabbit PMNs via the alternative complement pathway.

The effect on hemostatic parameters of two non-ionic contrast media, iopentol and iohexol in concentrations of 350 mg I/ml, were tested in vitro. The new medium iopentol had similar effects to those of iohexol, both with respect to the intrinsic coagulation system and platelet aggregation. As part of a human pharmacologic study the effects of iopentol on hemostatic parameters were tested in 8 volunteers in vivo. Iopentol induced a slightly decreased coagulability and aggregability in venous blood. It was concluded that the effects were of very little consequence for hemostasis as a whole.

An allotransplantation of a partly developed premolar from a 12-year-old daughter to her mother is reported. The tooth graft was selected by the use of HLA-A, -B, -C and DR typing and the MLC tests. Follow-up over a 3-year period included periodic identically taken radiographs, electric and galvanic pulp tests and tests for cytotoxic antibodies. Almost complete closure of the apex of the tooth has occurred with no sign of root resorption. The transplant has remained vital, and no production of antibodies against the graft has occurred.

Lipopolysaccharides (LPS) isolated from oral strains of Veillonella, Fusobacterium and Bacteroides stimulated the release of 45Ca from prelabeled fetal rat bones in culture. There was a typical dose-response relationship between the quantities of released 45Ca and LPS used for stimulation. Bacteroides-LPS proved to be the less active inducer of 45Ca release. LPS had no stimulating effect on the release of 45Ca from devitalized bone. The stimulated 45Ca release was paralleled by an increase in the culture medium of hydroxyproline and lactate. This, together with the findings of numerous osteoclasts in stained histological specimens of the experimental bones, indicates that LPS stimulated the osteoclasts to bone resorption. Heparin, which did not directly induce 45Ca release, potentiated the bone resorption stimulating capability of LPS. The lipid A and the polysaccharide portion of Fusobacterium LPS also stimulated bone resorption and, remarkably, the polysaccharide portion showed the greatest activity. This may explain the mode of action of LPS lacking a typical lipid A. It is suggested that stimulation of osteoclasts by LPS may result from activation of complement components by lipid A or its polysaccharide portion.

Phenol-water extracted lipopolysaccharides (LPS) from Veillonella, Fusobacterium nucleatum, Bacteroides fragilis and Bacteroides melaninogenicus were lethal for mice and 11-days-old chick embryos, pyrogenic in rabbits, and gelated Limulus amoebocyte lysate. Mouse lethality was considerably enhanced by actinomycin-D. In all test systems the endotoxin activity of Veillonella and Fusocbacterium LPS was comparable to that of LPS from Salmonella enteritidis, which was included as a reference endotoxin. The endotoxicity of the Bacteroides LPS was very low. While nanograms of the Veillonella and Fusobacterium LPS killed the chick embryos and gelated the Limulus lysates, microgram amounts of the Bacteroides LPS were needed to give positive reaction in the same test systems. As much as 74 microgram of the most active B. fragilis LPS were required to give a typical biphasic fever response in rabbits. A significant correlation was found between all test results (r = 0.90-0.98, p less than 0.001).

Exudate aspirated from wound chambers implanted subcutaneously on rabbits at different time intervals after local lipopolysaccharide (LPS) injection, showed a peak of chemotactic mediator concentration in vitro about two hours before the peak of polymorphonuclear lekocytes accumulated in vivo was demonstrated. Injection of LPS locally into the wound chambers three days after the first injection of LPS showed a reduced number of PMNs accumulated in the exudate. Antibodies to the LPS preparation were demonstrated in the exudate and serum by indirect haemagglutination of sheep erythrocytes before the second LPS injection. This antibody titre increased up to two weeks after the first LPS injection, and was slightly higher in the serum than in the exudate. Also, a migration inhibition factor (MIF) activity was demonstrated in the exudates formed. This MIF activity of the exudates increased after the second LPS injection. The increased titre of specific antibody may indicate an accelerated clearance of LPS, and the MIF activity may indicate a reduced response of PMNs to chemotactic mediators. However, the involvement of other biological mechanisms contributing to the decreased response, cannot be excluded.