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PubMed1990

Modification of D-galactosamine-induced liver damage in rats by intravenous injection of newly isolated intact splenic cells.

In rats of an inbred F344/DuCrj line, simultaneous injection of newly isolated intact splenic cells (derived from normal rats of the same strain) markedly modified and reduced the liver damage induced by treatment with D-galactosamine. When rats treated with D-galactosamine plus newly isolated intact splenic cells were compared with those treated with D-galactosamine alone, the former showed less atrophy of the liver, a smaller decrease in serum albumin, and lower serum levels of GOT, GPT, LDH, and total bilirubin, suggesting that the escape of these liver components into serum, which occurs when the liver is damaged, was suppressed in the former group. This effect was not observed when mitomycin C-treated splenic cells were injected. These results suggest that intact splenic cells injected intravenously play an important role in mediating the mechanisms responsible for repair of liver damage.

Animals↗
PubMed1986

Difference of 14C turnovers in brain and in transplanted glioma after intravenous injection of 14C-1-pyruvate into rats.

Carbon 14 from 14C-1-pyruvate injected intravenously into glioma-transplanted rats was incorporated into various compounds in the brain and in the tumor. In the brain the majority of activity was found in CO2 (60%), and minor activities were found in alanine, lactate (15%), glutamate, and aspartate, with decreasing order, 5 min after injection. In the tumor, at 5 min, the largest activity was in lactate (56%), and lower activities were found in CO2 (24%), alanine, glutamate, and aspartate. The total 14C concentration in the tumor was twice that in the brain at 5 min and 15 min. The result was in accordance with the prediction that in brain, where the mitochondrial function is active, 14C-1-pyruvate will be oxidized completely into 14CO2, and that in tumor, where the mitochondrial function is insufficient, 14C-1-pyruvate will be converted only into 14C-lactate and prevent further degradation. It may be assumed that this difference in the turnover of 14C of 14C-1-pyruvate between brain and tumor could constitute a basis for the 'hot' visualization of human brain tumor using cyclotron-produced 11C-1-pyruvate and positron-emission tomography.

Animals↗
PubMed1997

Circulatory kinetics of intravenously injected 238Pu(IV) citrate and 14C-CaNa3-DTPA in mice: comparison with rat, dog, and reference man.

New ligands for in vivo chelation of Pu(IV) are being synthesized and evaluated in mice for efficacy and toxicity. Biokinetic studies of the new ligands, CaNa3-DTPA, and Pu(IV) are major components of those investigations. Young adult female mice were injected intravenously (iv) with 3H-inulin, 14C-CaNa3-DTPA, or 238Pu(IV) citrate to provide baseline data for plasma clearance, tissue uptake, and excretion rates and to determine the dilution volume (VOD) and renal clearance rate (RC) of filterable substances. Published plasma clearance data for iv-injected 14C-CaNa3-DTPA and Pu(IV) citrate in Reference Man, dog, and rat were collected. Based on combined data for 3H-inulin and 14C-CaNa3-DTPA, VOD = 17% of body weight and RC = 18 mL kg(-1) min(-1) for mice. Retention of 14C-CaNa3-DTPA in the four species is proportional to body weight and inversely proportional to RC: Integrals of the retention of 14C-CaNa3-DTPA from R(t) = 1.0 to R(t) = 0.05 are 108, 43, 28, and 10 DF min, respectively, for Reference Man, dog, rat, and mouse. Clearances of iv-injected Pu(IV) citrate from plasma are in the same order: The plasma curve integrals from injection to 1440 min are 840, 640, 280, and 67 DF min, respectively, for Reference Man, dog, rat, and mouse. In mice, a large fraction of newly injected Pu(IV) is rapidly transferred to the interstitial water of bulk soft tissue (excluding liver and kidneys), from which it is cleared at the same rate as from the plasma. Rapid plasma clearance, escape into interstitial water (22%ID at 20 min), significant early urinary excretion (8%ID in 12 h), and prompt deposition in liver and skeleton (complete in 12 h) are evidence of inefficient binding to plasma protein (mainly transferrin) of newly injected Pu(IV) in mice. Conversely, slow plasma clearance, little early urinary excretion, and delayed deposition in liver and skeleton reflect more efficient binding by transferrin of newly injected Pu(IV) in Reference Man and dog. Pharmacokinetic parameters (effective dosage, effective concentration) of CaNa3-DTPA, alone or combined with plasma Pu(IV) integrals, yielded only qualitative predictions of the relative efficacies of CaNa3-DTPA therapy in four species. The need for improved models of Pu(IV) and ligand biokinetics and the suitability of the three animals for predicting chelation therapy outcomes in humans are discussed.

Animals↗
PubMed1980

Serum and tissue distribution of benzol[a]pyrene from intravenously injected chylomicrons in rat in vivo.

Rats were injected intravenously with chylomicrons (CM) containing benzo[a]pyrene (B[a]P), a carcinogenic aromatic hydrocarbon. The disappearance of B[a]P paralleled the removal of CM, both having a rapid initial decay and a secondary slow decay. After 5 min, at the end of the rapid phase, blood contained 19% of the total injected B[a]P, with 6% in blood cells and 13% in serum. At 60 min, serum contained 5% and blood cells 6% of the total B[a]P. During the slow phase, further distribution of B[a]P within serum albumin and various lipoproteins occurred, most of the label being in low density and very low density lipoproteins. Highest tissue specific activities of [3H]B[a]P were in the lung, liver and kidney tissues. These results suggest that in the rat, distribution of ingested polycyclic aromatic hydrocarbons in vivo tends to be primarily determined by the catabolism of chylomicrons.

Animals↗
PubMed1982

Lethal effect of the intravenous injection of H-2 alloantigen activated T cells.

T cells of C57BL/6J (B6) mice activated in vitro against the K and D determinants of the H-2d haplotype, and expanded in tissue culture in the presence of interleukin 2, were capable of rapidly killing lethally irradiated BALB/c recipients when injected intravenously. Mice given 10(6), 10(7) and 10(8) such T cells survived 10.5, 8.5 and 0.5 days respectively. Mice given irradiation only survived 10.5 days. Mice given 10(8) B6 T cells activated against all determinants of a third party haplotype (H-2k) survived 8.5 days. Respiratory distress developed within 3 hr of injection in mice given 10(8) T cells activated against the H-2 alloantigens of the recipient haplotype, and at autopsy their lungs showed pulmonary congestion, focal obliteration of the alveolar space and thickening of alveolar interstitial tissue with fibrin, red cell and a mononuclear cell infiltrate. These findings may have relevance to the use of cellular immunotherapy.

Animals↗
PubMed2002

[Repeated metallic mercury intravenous injections for doping].

In this article we described a 24 year-old patient, suffering from nephropathy of unknown origin, who was admitted to the Clinic after having tried to commit suicide for the third time by overusing tricycle antidepressant drugs (TLPD) and ethanol. During toxicological tests the serum TLPD level was 548 micrograms/L and the serum ethanol level was 2.1 g/L. His chest X-ray showed the presence of several metal particles of approx. 1.5 mm in diameter disseminated in both lungs, which could have been particles of metallic mercury. When the state of coma was over the patient admitted that for the past three years he had many times injected intravenously a small amount of metallic mercury (about 0.5 ml/dose) to improve his strength, speed and physical fitness. Tested serum mercury level was 300 micrograms/L and urinary mercury excretion 500 micrograms/L/24 hours.

Adult↗
PubMed1980

Effect of intravenously injected killed pneumococci on leukocytes, complement, and phagocytosis in rabbits.

A pneumococcal infection may be lethal in the absence of overwhelming pulmonary involvement, and death may occur even after the organisms have been killed with antibiotics. The mechanism of death is not understood but may be related to circulating pneumococcal products. For investigating the effects of nonviable pneumococci on several host defense mechanisms, rabbits were injected intravenously with 4 X 10(8) colony-forming units of killed sonified type 13 or type 29 pneumococci. Blood was sampled periodically for the next 24 h, and the following were measured: (i) circulating levels of leukocytes; (ii) activity of the classical and alternate complement pathways; and (iii) ability of the serum to opsonize pneumococci for ingestion and killing by polymorphonuclear leukocytes. Saline-injected control rabbits showed no change in any of the functions. Nonimmune rabbits injected with either pneumococcal serotype showed progressive and profound leukopenia, no change or an increase in classical and alternate complement pathway activity, and a profound reduction in the serum-opsonizing capcity for pneumococci of the same serotype as that used in the injection. The opsonizing capacity remained normal for the other serotype. When a previously immunized animal was injected, the opsonizing capacity for the homologous organism remained intact, but leukopenia nervertheless occurred.

Animals↗
PubMed1998

Regional distribution of 203PbCl2 in the mouse after intravenous injection.

UNLABELLED: Lead is a known neurotoxicant, and concentrations of lead in the CNS after acute exposure to low doses have not been studied in detail. In this investigation, the temporal distribution of lead ([203Pb]), injected intravenously at no-carrier-added (NCA) (0.6-0.7 mumol/kg) and at carrier-added (7.0-62.3 mumol/kg) levels was determined in mice. Concentrations of [203Pb] were measured in major organs and in different regions of the brain. Ex-vivo autoradiographic visualization was used to confirm and extend the brain distribution findings. RESULTS: The highest concentrations of NCA [203Pb] were observed initially in the kidneys (52% of the injected dose (ID)/g at 1 hr) and liver (10.5% ID/g at 30 min). Uptake into bone occurred gradually, reaching 25% ID/g at 24 hr. In accord with previous reports, excretion of the tracer was very slow. Approximately 80% of total ID remained in the body after 24 hr and 68% at 48 hr. Interestingly, in the mouse brain, the highest levels of [203Pb] were noted in the area of the hypothalamus. At all times between 30 min and 16 hr postinjection, and at all Pb dose levels injected, the accumulation of [203Pb] in the hypothalamic region exceeded that in all other brain regions examined. Autoradiography performed at the 16 hr time point confirmed the high uptake and strong retention of [203Pb] by the hypothalamus. These studies afford new insight into the distribution of acutely administered lead in the brain, and may have implications for the understanding of some of the neurotoxic effects of lead.

Animals↗
PubMed1987

Pharmacologic effects of iopentol after intravenous injection in healthy volunteers. Preliminary report.

The effects of the first injections in humans of iopentol, a new non-ionic contrast medium, are briefly reported. Detailed descriptions will be published elsewhere. Iopentol was well tolerated when injected intravenously into 24 healthy male volunteers in doses of 300 to 1,200 mg I/kg body weight and was excreted almost entirely in the urine in unchanged form. The results indicate that iopentol may be used in clinical trials in patients.

Adult↗
PubMed1979

[Prolactin after repeated intravenous injections of cimetidine].

To 4 normal women a bolus of mg 400 of cimetidine was injected intravenously once an hour for three hours in succession and plasma prolactin behaviour studied. No depletion in prolactin pituitary storage was observed in all subjects. The possible usefulness of cimetidine for clinical diagnostic purposes is discussed.

Adult↗
PubMed2001

Changes in murine bone marrow macrophages and erythroid burst-forming cells following the intravenous injection of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP).

In order to explore the effect on bone marrow macrophages of liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP), mice were injected intravenously with a preparation of such liposomes at a dose known to deplete spleen and liver macrophages. Two days later, the macrophages in the marrow of the femoral bones were quantified by flow cytometry using a macrophage-specific monoclonal antibody (F4/80), and their ultrastructure and phagocytic activity towards zymosan particles was assessed. To determine the effect on erythropoiesis of liposome-encapsulated Cl2MDP-induced changes in bone marrow macrophages, red blood cell parameters and the formation of erythroid burst-forming unit (BFU-E)-derived colonies in vitro were evaluated. In mice injected with liposome-encapsulated Cl2MDP, there was a 54% and 67% decrease in the total number of bone marrow macrophages as compared to uninjected controls and mice treated with empty liposomes, respectively. Moreover, residual macrophages showed an abnormal ultrastructure, with reduced numbers of crystalloid inclusions and increased numbers of large myelin figures. However, the phagocytic activity of these cells was unimpaired or slightly enhanced. In mice injected with liposome-encapsulated Cl2MDP there was an approximately 60% decrease in the percentage and total number of circulating reticulocytes and a 54% reduction in the BFU-E number, demonstrating deregulation of erythropoiesis under conditions of macrophage loss and impairment. The results suggest that mice treated with liposome-encapsulated Cl2MDP are a model for studying the role of macrophages in erythropoiesis.

Animals↗
PubMed1978

Haematological, serological and pathological effects in chicks of one or more intravenous injections of Salmonella gallinarum endotoxin.

Abnormalities appeared a few hours after groups of 14-day-old chicks (Gallus domesticus) were injected intravenously with 15 mg/kg of endotoxin (LPS) from Salmonella gallinarum. Clinical illness without mortality was accompanied by significant (P less than 0.05) falls in body temperature, bursa weight, the main haematological parameters, serum iron (SI) and transferrin saturation (TS) and a significant increase in unsaturated iron-binding capacity. All responses, apart from bursa weight, SI values and total and differential white-cell counts, returned to normal within 24 to 48 h. LPS given daily for three consecutive days did not cause changes in the main haematological parameters during the 48 h period following the third injection. However body and bursa weight and heterophil counts were significantly depressed, whereas body temperature, SI and TS were affected biphasically, being first depressed and then raised above normal. Chicks injected with LPS daily for six consecutive days showed broadly similar responses but a persistent microcytosis was also present.

Animals↗
PubMed1996

Comparative studies of the fate of free and liposome-entrapped hydroxypropyl-beta-cyclodextrin/drug complexes after intravenous injection into rats: implications in drug delivery.

Inclusion complexes of 14C-labelled hydroxypropyl-beta-cyclodextrin (HP beta-CD) with tritiated dehydroepiandrosterone (DHEA), retinol (RET) and dexamethasone (DEX) were entrapped in the aqueous phase of liposomes composed of distearoyl phosphatidylcholine. Incubation of liposome-entrapped complexes in the presence of rat blood plasma at 37 degrees C resulted in complex dissociation and drug leakage in the media at a rate which was minimal for DEX/HP beta-CD (11%), modest for RET/HP beta-CD (23%) and considerable for DHEA/HP beta-CD (56%; 60 min). In contrast, the HP beta-CD moiety of the complexes was retained by liposomes quantitatively. Free complexes injected intravenously into rats were cleared rapidly from the circulation with most (up to 94%) of the HP beta-CD moiety recovered in 24 urine together with lesser and variable amounts of drug (up to 46% of the dose) in a pattern (DHEA < RET < DEX) that was consistent with the extent of drug association with HP beta-CD in the presence of plasma. A significant proportion of the drugs (up to 25% of the dose)(but very little HP beta-CD) was removed by the liver where drugs were catabolised rapidly, probably following complex dissociation and transport to the tissue via plasma proteins. Injection of entrapped complexes revealed that liposomes alter their pharmacokinetics with only 6-13% of HP beta-CD and a moderate proportion of drugs (up to 26% of the dose) recovered in the urine. Much of the HP beta-CD moiety of the liposomal complexes was recovered in the liver (up to 83%) and spleen (up to 13% of the dose) by 30 min after injection, together with a variable proportion of drugs in a pattern (DHEA < RET < DEX) which reflected that of complex dissociation in vitro. Longer term experiments where animals injected with liposome-entrapped complexes were killed at time intervals (up to 24 days), revealed that HP beta-CD is eliminated from the tissues, albeit at a very slow rate. Moreover, the metabolism of individual drugs in the tissues following vesicle disintegration, appeared to depend on the rate of complex dissociation with DEX, for instance, reaching values of 4-6% (liver) only after 14 days. It is concluded that administration of drug/cyclodextrin inclusion complexes via liposomes could serve as a means to control the action of a wide range of therapeutic agents.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed2001

Distribution of iodine 125-labeled alpha1-microglobulin in rats after intravenous injection.

The 28-kd plasma protein alpha(1)-microglobulin is found in the blood of mammals and fish in a free, monomeric form and as high-molecular-weight complexes with molecular masses above 200 kd. In this study, iodine 125-labeled free and high-molecular weight rat alpha(1)-microglobulin (a mixture of alpha(1)-microglobulin/alpha(1)-inhibitor-3 and alpha(1)-microglobulin/fibronectin complexes) were injected intravenously into rats. The distribution of the proteins was measured by using scintillation camera imaging. Both forms of (125)I-labeled alpha(1)-microglobulin were rapidly cleared from the blood, with a half-life of 2 and 16 minutes for the initial and late phase, respectively, for free alpha(1)-microglobulin; and a half-life of 3 and 130 minutes for the initial and late phase, respectively, for the complexes. After 45 minutes, 6%, 16%, 27%, 13%, and 34% of the free (125)I-labeled alpha(1)-microglobulin and 18%, 21%, 6%, 10%, and 42% of the (125)I-labeled alpha(1)-microglobulin complexes were found in the blood, gastrointestinal tract, kidneys, liver, and the remainder of the body, respectively. The local distribution of injected (125)I-labeled alpha(1)-microglobulin in intestines and kidneys was investigated by microscopy and autoradiography. In the intestine, both forms were distributed in the basal layers, villi, and luminal contents. The results also suggested intracellular labeling of epithelial cells. Well-defined local regions containing higher concentrations of injected protein could be seen in the intestine. In the kidneys, both forms were found mostly in the cortex. Free (125)I-labeled alpha(1)-microglobulin was found predominantly in epithelial cells of a subset of the tubules, whereas the (125)I-labeled complexes were more evenly distributed. Intracellular labeling was indicated for both alpha(1)-microglobulin forms. The results thus indicate a rapid transport of (125)I-labeled alpha(1)-microglobulin from the blood to most tissues.

Animals↗
PubMed1997

Induction of hepatic egg granuloma hyporesponsiveness in murine schistosomiasis mansoni by intravenous injection of small doses of soluble egg antigen.

This work was designed to test whether hyporesponsiveness to schistosomal egg antigen (SEA) was associated with reduction in size of hepatic granulomas. Multiple small doses of SEA (10 micrograms x 4) were injected intravenously (i.v.) into C57B1/6 mice either at 7 or 30 days prior to cercarial exposure. Eight weeks postinfection, hepatic histopathology and granuloma diameter were studied. SEA-induced lympho-proliferative response, splenic cytokines (IL-2, IL-4 and IL-5) and serum antischistosomal IgG were assessed. Worm burden and tissue egg load were counted. Compared to infected controls, the SEA-treated groups showed decrease in granuloma diameter, remarkable increase in the percentage of degenerated ova within hepatic granulomas and amelioration of histopathological changes. SEA lymphoproliferative response, and levels of Il-2 and IL-4, were lower in SEA-treated groups than infected controls. The levels of IL-5 and antishistosomal IgG were comparable to the infected controls. The intensity of infection was not influenced by i.v. injection of SEA. The present data show that i.v. administration of multiple small doses of SEA induced granulomatous hyporesponsiveness with amelioration of hepatic pathology and acceleration of egg destruction.

Animals↗
PubMed1977

Microembolism in experimental septic shock. Distribution of platelets and fibrinogen after intravenous injection of disintegrated Pseudomonas bacteria to dogs.

Platelets were labelled with 51Cr, fibrinogen with 125I and erythrocytes with 59Fe. Disintegrated Pseudomonas bacteria were injected intravenously and radioactive measurements were made on whole blood; tissue biopsies and clottable fibrinogen. After the infection there was an immediate but transient increase of 51Cr activity in the lung concomitant with a decrease in platelet count and 51Cr activity of blood. In the liver there was a less pronounced increase of 51Cr activity. The fibrinogen concentration decreased slightly, paralleled by the 125I activity of whole blood and of clottable fibrinogen, whereas the 125I activity in the lung and liver remained fairly constant. There was no changes of 51Cr activity or 125I activity in biopsies from muscle, pancreas, small intestine, kidney or spleen. During the experiment (3h) there were no signs of significant disseminated intravascular coagulation other than platelet aggregation. A consumption of fibrinogen related to the formation of fibrin plugs could not be detected. After injection of disintegrated Pseudomonas bacteria reversible platelet aggregates were formed and temporarily trapped in the pulmonary microcirculation. This microembolism might induce tissue damage and could be of importance for the development of septic pulmonary complication.

Animals↗
PubMed1994

[Three-dimensional imaging of portal and hepatic veins using helical CT with intravenous injection of contrast medium].

The authors developed a simple new method for obtaining three-dimensional helical CT images that simultaneously depict both the portal and hepatic veins. One hundred ml of contrast medium was injected intravenously, and helical CT was carried out. Three-dimensional venous images were successfully displayed with rotational movement on the CRT monitor. The new method provided high-quality images in which the anatomical relationship between the portal and hepatic venous systems could be clearly visualized. This information was useful in helping angiographers to successfully perform transjugular intrahepatic portosystemic shunt and will be of great value for the presurgical planning of hepatic resection.

Adult↗