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PubMed1977

Vascular changes in the lungs of rats after the intravenous injection of pyrrole carbamates.

The effects on the lung of some synthetic compounds related to monocrotaline pyrrole have been studied and compared with those previously found with that compound. When injected into a systemic vein doses of pyrrole mono- and dicarbamate produced acute pulmonary oedema. Pyrrole alcohol and ethyl carbamate had no such effect and although furyl carbamate did not cause pleural effusion in rats it did so in mice. Like monocrotaline pyrrole, when injected into other vessels the pyrrole carbamates produced oedema in the region of the first capillary bed encountered. When colloidal carbon was injected intravenously after the pyrrole carbamates, carbon "labelling" was seen in both the post-capillary venules and the capillaries of the lungs. On the whole, venular "labelling" occurred before capillary "labelling" which was best seen when the carbon was injected more than 4 hr after the pyrrole. The distribution of the carbon as seen by electron microscopy is described. No "labelling" was seen after furyl carbamate. The effects of the synthetic pyrrole esters were similar to those of monocrotaline pyrrole. Although both the pyrrole carbamates were less active on a molecular basis they had a broader action on the pulmonary vasculature causing venular as well as capillary "labelling". To affect the lungs acutely the compound had to have the pyrrole ring structure and at least one ester side-chain.

Animals↗
PubMed1993

Effects of anaesthesia on the removal from plasma of intravenously injected chylomicron-like lipid emulsions in rats and mice.

1. In order to find an anaesthesia with minimum perturbation to the metabolism of chylomicrons, the effects of seven different anaesthetic agents on clearance from plasma of chylomicron-like emulsions were compared. 2. Avertin, urethane, fentanyl, and a ketamine/xylazine mixture all slowed the removal from plasma of emulsion triolein and cholesteryl oleate. The steroid anaesthetic althesin slowed the clearance of emulsion cholesteryl oleate without affecting the removal from plasma of emulsion triolein. Nembutal when injected intravenously at a hypnotic dose did not affect the clearance of emulsion triolein or cholesteryl oleate, whereas at the anaesthetic dose, nembutal slowed the clearance rate of both labelled lipids. 3. Except for althesin, which did not affect the plasma clearance of triolein, fractional clearance rates of emulsion triolein and cholesteryl oleate calculated from blood samples taken during 12 min after injection were significantly slower in the anaesthetized groups compared with controls. However, with avertin, althesin, nembutal and ketamine/xylazine, amounts of radiolabelled triolein and cholesteryl oleate remaining in plasma 25 and 30 min after injection were comparable with the control. Radioactive lipids in plasma remained much higher in rats treated with urethane and fentanyl-fluanisonium even 30 min after injection. 4. Avertin was simple to administer and produced a suitable depth of anaesthesia for minor surgery, tail vein injections and blood sampling, whereas althesin and the ketamine/xylazine mixture required supplementary doses to maintain anaesthesia towards the end of the experiment. We concluded that anaesthesia is best avoided for studies of chylomicron clearance. Avertin is the preferred agent if anaesthesia must be used, for example in newborn rats or in mice.

Anesthetics↗
PubMed1975

Lysosomal degradation of cell organelles. I. Ultrastructural analysis of uptake and digestion of intravenously injected mitochondria by Kupffer cells.

An experimental model comparable to autophagocytosis is presented to evaluate lysosomal degradation of biologic membranes in vivo. This design takes advantage of the efficient phagocytic capacity of Kupffer cells. For this purpose, mitochondria were isolated from one rat liver (inbred strain) and subsequently injected intravenously into a series of rats, which were sacrificed at various time points. The uptake and intralysosomal digestion were examined by electron microscopy. Mitochondria were seen in the sinusoids and attached to the surface of Kupffer cells 1 to 3 minutes after injection. One or two mitochondrial profiles were trapped in cavelike structures often embraced by long hyaloplasmic pseudopods. By 5 and 10 minutes, the mitochondria were in single membrane-bound phagosomes within the Kupffer cells and early signs of mitochondrial alterations were present, e.g., loss of cristae and condensation. At 30 minutes and 1 hour the mitochondria were seen in large vacuoles which contained up to 20 profiles in a single section. The mitochondria showed evident signs of digestion such as membrane fragmentation and flocculent densities. By 4 hours and especially by 8 hours, most digestive vacuoles were laden with flocculent membrane debris. By 24 hours, the Kupffer cells showed multiple lysosomal structures which were irregular in shape and small. These often contained a number of lipid-like droplets of various electron densities and pentalaminar structures. By 2 and 5 days, the Kupffer cells had returned to their normal appearance although the lysosomal apparatus was still prominent. No uptake of mitochondria was seen in endothelial cells, fat-storing cells, or hepatocytes. It is concluded that lysosomes have an efficient capacity to digest mitochondria. Some lipid remnants are not completely or slowly degraded by Kupffer cell lysosomes but remain in "residual bodies" for up to 1 or 2 days.

Animals↗
PubMed1986

Transfer of protein antigens into milk after intravenous injection into lactating mice.

We investigated the transfer of bovine serum 125I-albumin (125I-BSA), bovine 125I-gamma-globulin (125I-BGG), 125I-ovalbumin (125I-OVA), and 125I-beta-lactoglobulin (125I-BLG) from the blood into the milk of lactating mice. Equal amounts (by weight) of the radiolabeled proteins were injected intravenously into mice 1 wk postpartum. Total radioactivity, trichloroacetic acid-precipitable radioactivity, and specifically immunoprecipitable radioactivity were measured in serum, mammary gland homogenate, and milk. Clearance of immunoreactive OVA (iOVA) and iBLG from the circulation was more rapid than iBSA and iBGG. The radioactivity in mammary tissue associated with BSA and BGG was greater than 70% immunoprecipitable throughout the 4-h test interval; 125I-OVA and 125I-BLG were less than 12% precipitable 1 and 4 h after injection. In milk obtained at 4 h, there was an approximately 10-fold greater accumulation of iBSA or iBGG than of iOVA or iBLG. These experiments demonstrate that protein antigens differ in their ability to transfer from maternal circulation into milk. The transfer into milk appeared to be in proportion to persistence of the antigens in the maternal circulation.

Animals↗
PubMed1975

Distribution of radioactivity in tissues after the intravenous injection of free and acrylic particle bound-porcine 125I-neurophysin-I into rats and rabbits.

Porcine neurophysin-I iodinated with Na125I was injected intravenously into rats and rabbits, and the rate of disappearance of radioactivity from the peripheral system was measured. Radioactively-labeled neurophysin bound to polymethylmethacrylic particles was similarly infected into the animals. The half-time for the loss of radioactivity from samples of whole blood was 6.1--6.4 min as determined over the first 5 min after administration of the protein. There was no significant difference in the half-time calculated when the radioactivity present in the trichloroacetic acid-insoluble material present in the se-um was measured. 15 min after the injection of labeled protein there was a maximum and massive uptake of radioactivity in the kidney consistent with this tissue's being important in the degradation of neurophysin. Immunoperoxidase histochemical techniques were applied to formalin-fixed kidney slices and demonstrated the presence of neurophysin-like material localized in the cells of proximal tubules of the cortex and medulla. On binding neurophysin to acrylic particles there was approximately a 10-fold increase in the uptake of radioactivity in the lungs and a 33% reduction in activity in the kidneys, as measured at the 15-min time interval. Of the other tissues studied, excluding the thyroid gland and lungs, the uterus demonstrated the greatest uptake of radioactivity of fat tissue had the least accumulation of radioactive label.

Animals↗
PubMed1975

[Ultrastructure and morphogenesis of ceroid pigment. I. Phagocytosis and formation of lipid-containing lysosomes in Kupffer Cells after intravenous injection of unsaturated lipids (author's transl)].

Wistar rats were injected intravenously with cod liver oil emulsion. The phagocytosis of these lipids by the Kupffer cells as well as the formation of lipid-containing lysosomes were studied electron microscopically within a period of 5 min to 12 hrs. The emulsified lipids are incorporated into the cytoplasm by membrane-vesiculation. The lipid-containing phagocytic vacuoles (lipophagosomes) were transformed into secondary lysosomes (lipophagolysosomes). This change occurs in two phases. Immediately after phagocytosis the lipophagosomes are provided with lysosomal enzymes by fusion with pre-existent lysosomes (dense bodies) of the Kupffer cells. These are mainly the so-called small homogenous dense bodies which are probably primary lysosomes of the type of "storage granules". In the second phase which begins 15-30 min after the injection; the fusion of lipophagosomes with newly produced primary lysosomes within the Golgi apparatus is predominant. Therefore, the enzyme supply of the phagocytic vacuoles does not occur at once but in small amounts during a longer period. The lipids slowly change into an amorphous electron-dense mass 12 hrs after the injection. Obviously, these changes are the first step to the formation of ceroid pigment.

Acid Phosphatase↗
PubMed2001

Activation of prostanoid EP(3) and EP(4) receptor mRNA-expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide.

Systemic inflammation activates central autonomic circuits, such as neurons in the pontine parabrachial nucleus. This activation may be the result of afferent signaling through the vagus nerve, but it may also depend on central prostaglandin-mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune challenge express prostaglandin receptors of the EP(3) and EP(4) subtypes, but it remains to be determined if the prostaglandin receptor-expressing neurons are identical to those that respond to immune stimuli. In the present study, bacterial wall lipopolysaccharide was injected intravenously in adult male rats and the expression of c-fos mRNA and of EP(3) and EP(4) receptor mRNA was examined with complementary RNA probes labeled with digoxigenin and radioisotopes, respectively. Large numbers of neurons in the external lateral parabrachial subnucleus, a major target of vagal-solitary tract efferents, expressed c-fos mRNA. Quantitative analysis showed that about 60% (range 40%-79%) of these neurons also expressed EP(3) receptor mRNA. Conversely, slightly more than 50% (range 48%-63%) of the EP(3) receptor-expressing neurons in the same subnucleus coexpressed c-fos mRNA. In contrast, few EP(4) receptor-expressing neurons were c-fos positive, with the exception of a small population located in the superior lateral and dorsal lateral subnuclei. These findings show that immune challenge activates central autonomic neurons that could be the target of centrally produced prostaglandin E(2), suggesting that synaptic signaling and paracrine mechanisms may interact on these neurons.

Acute-Phase Reaction↗
PubMed1997

Schistosoma mansoni: unisexual infections sensitized mice for granuloma formation around intravenously injected eggs.

Mice carrying unisexual infection with male or female Schistosoma mansoni for 9 weeks developed accelerated and augmented reactions to S. mansoni eggs injected intravenously. The size of circumoval granulomas observed in the lungs of unisexually infected mice did not differ significantly from the reactions seen in bisexually infected mice. Tissue eosinophilia in the granulomas was also augmented similarly over that in naive mice by unisexual or bisexual infection. The cross-reactivity between worm and egg antigens is relevant to the development of acute toxemic schistosomiasis mansoni and, perhaps, to the consideration of antigens to be used for vaccination against S. mansoni infection.

Animals↗
PubMed1987

The organ distribution and circulation time of intravenously injected colloidal carriers sterically stabilized with a block copolymer--poloxamine 908.

Colloidal carriers injected intravenously are normally removed rapidly and efficiently by the liver and this represents a major barrier to drug targeting. By coating model microspheres and emulsions with a block co-polymer (poloxamine) it has been possible to keep the carrier circulating in the vascular compartment with little or no uptake by the reticuloendothelial system.

Animals↗
PubMed1991

Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers.

For a better understanding of low molecular weight heparin pharmacokinetics, 99m technetium labelled heparin and enoxaparin were injected intravenously to four normal volunteers, after approval by the Ethics Committee and preliminary animals studies. In vitro and in vivo, the labelled products proved to be stable and identical to the non-labelled drugs. Radioactivity curves in blood, organs and urines were similar for both products. Anti Xa plasma half-life was 3 times longer for enoxaparin than for heparin. Anti IIa plasma half-lives were similar. However, radioactivity persisted much longer than biological activities for both products. After chromatography, most of the radioactivity was bound to AT III, where an anti Xa activity peak was also detected. The anti Xa activity peak seen after adding AT III to plasma was much higher with heparin than with enoxaparin. In urine, biological activities, measured with AT III supplementation, were higher with enoxaparin than with heparin. These results suggest that phenomena other than biodistribution are responsible for the differences in pharmacokinetics observed between these two products. The two most likely explanations are differences in metabolism and/or a release of an endogenous factor.

Adult↗
PubMedDate not supplied

Radioactive labelling of lipids in rat neurosarcoma by intravenous injection of [1-14C]-octadecenol.

Radioactivity from cis-9-[1-14C]octadecenol, injected intravenously into rats bearing neurosarcoma, is incorporated to a significantly greater extent into tumor than into muscle. In the lipids of both tissues, radioactivity is incorporated predominantly into the acyl moieties, rather than into the alkyl or alk-1-enyl moieties, of diradylglycerophosphocholines, diradylglycerophosphoethanolamines, and triradylglycerols.

Animals↗
PubMed1990

Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers.

The pharmacokinetics of Gd-DOTA meglumine in humans were evaluated in six healthy male volunteers. The agent was injected intravenously at 0.1 mmol/kg over approximately 2 minutes. Its behavior was found to be similar to that of urographic and angiographic iodinated contrast media with a plasma elimination half-life of 91 +/- 14 minutes (mean +/- standard deviation [SD]), a small distribution volume of 171.0 +/- 19.7 mL/kg and rapid urinary excretion. The results suggest rapid passive extravascular diffusion of gadolinium (Gd)-DOTA in the interstitial space without intracellular penetration, followed by a rapid urinary excretion via glomerular filtration. Furthermore, the results are consistent with animal data that showed that the compound does not cross the normal blood brain barrier. Its plasma pharmacokinetics appeared to be similar to those reported for Gd-DTPA. No relevant biological effects were seen with Gd-DOTA, especially in regard to serum iron and bilirubin levels.

Adult↗
PubMed1978

Biodistribution of intravenously injected [14C] doxorubicin and [14C] daunorubicin in mice: concise communication.

[14C] doxorubicin (adriamycin) and [14C] daunorubicin (daunomycin) are cardiotoxic antibodies used in cancer therapy. These drugs were examined as possible agents for the measurement of regional myocardial blood flow. The antibiotics were injected intravenously into mice, which were then killed after various intervals. At a chemical dosage of 0.5 mg per kilogram, the content of the heart never exceeded 0.60% of the administered dose for doxorubicin and 0.55% for daunorubicin. The cardiotoxic effect of these drugs, therefore, is probably related to a specific sensitivity of the heart, rather than to an avid uptake of the drugs by the cardiac muscle. Further studies seem warranted, using a lower chemical dosage and higher specific activity.

Animals↗
PubMed1993

Vasogenic edema induced by compression injury to the spinal nerve root. Distribution of intravenously injected protein tracers and gadolinium-enhanced magnetic resonance imaging.

The function of the blood-nerve barrier appears quite unique in the nerve root. Protein tracers that were injected into the subarachnoid space passed through the nerve root sheath and entered into the capillary lumen in the endoneurial space but tracers that were injected intravenously did not appear in the endoneurial space. Marked extravasation of protein tracers in the nerve root was induced at the compressed part by strong compression (60 gram force, 30 gram force) and capillaries in the nerve root showed opening of the tight junction accompanied by an increase in vesicular transport under the electron microscope. This situation was reflected as high intensity on Gadolinium-enhanced magnetic resonance imaging. In twenty-one of fifty patients with lumbar disc herniation, the affected nerve root was strongly enhanced by Gadolinium-diethylene-triaminepentaacetic acid, indicating that the blood-nerve barrier in the affected nerve root was broken and intraradicular edema was produced in these cases.

Adult↗
PubMed1981

Compatibility of netilmicin sulfate injection with commonly used intravenous injections and additives.

The compatibility and stability of netilmicin sulfate in a concentration of 3 mg/ml in 37 intravenous injections and in 5% dextrose and 0.9% sodium chloride injection with 26 commonly used additives were studied. Compatibility between an intravenous administration set and selected admixtures were also evaluated. The admixtures were stored at 4 and 25 degrees C for seven days. After mixing and on days 1, 3, and 7, all admixtures were evaluated for netilmicin potency, pH, color, osmolarity, and clarity. A microbiological assay was used to measure netilmicin potency. No changes in netilmicin potency, pH, osmolarity, color, or clarity were observed in any of the 37 netilmicin sulfate admixtures. Similarly, no changes in pH, osmolarity, or clarity were seen in the admixtures of netilmicin sulfate with a second additive. Netilmicin activity was retained for seven days in 22 of the 26 admixtures with a second additive. Netilmicin sulfate in admixtures with multivitamin injection or vitamin B complex (Upjohn) was stable for only one day; with diphenhydramine hydrochloride or neostigmine methylsulfate, for only three days. No incompatibilities between the intravenous infusion set and admixtures of netilmicin sulfate were apparent. Netilmicin sulfate injection is compatible and stable for at least seven days stored at 4 and 25 degrees C when mixed in 37 intravenous injections, and when mixed individually with 22 additives in 5% dextrose and 0.9% sodium chloride injection.

Colorimetry↗
PubMed1987

Pharmacokinetics of leucovorin (D,L-5-formyltetrahydrofolate) after intravenous injection and constant intravenous infusion.

The pharmacokinetics of the active and inactive diastereoisomers of leucovorin and its active metabolite, 5-methyltetrahydrofolate (5-CH3-THF) were studied after iv injection of leucovorin in normal human subjects at a dose of 28 mg/m2, and in patients given 500 mg/m2 daily by constant iv infusion for a 5.5 day period. In both studies the plasma half-life (t1/2) of the active isomer, L-formyltetrahydrofolate (CHO-THF), was only 32 to 35 minutes, whereas the inactive isomer, D-CHO-THF had a plasma t 1/2 of 352 to 485 minutes. During constant infusion, the plasma levels reached plateaus of 2.33 and 37.5 microM for L-CHO-THF and D-CHO-THF, respectively. The inactive isomer was cleared from plasma only by urinary excretion of the unchanged drug. The active isomer was also excreted unchanged in the urine but in addition was extensively metabolized to the active metabolite L-5-CH3-THF. The active metabolite achieved a plasma level of 4.85 microM during constant infusion and appeared to have a longer t 1/2 after constant infusion than was observed after iv injection. Furthermore a larger apparent volume of distribution (Vd) of 5-CH3-THF was obtained in the constant infusion study. These findings suggest that constant iv infusion of large doses of leucovorin can considerably expand the intracellular pools of active folate. The consequence of the extensive accumulation of the inactive isomer, D-CHO-THF, is not known. However, the small Vd of D-CHO-THF suggests that it does not extensively accumulate in tissues.

Biotransformation↗
PubMed2001

Pharmacokinetics and adverse effects of butorphanol administered by single intravenous injection or continuous intravenous infusion in horses.

OBJECTIVE: To determine an infusion rate of butorphanol tartrate in horses that would maintain therapeutic plasma drug concentrations while minimizing development of adverse behavioral and gastrointestinal tract effects. ANIMALS: 10 healthy adult horses. PROCEDURE: Plasma butorphanol concentrations were determined by use of high-performance liquid chromatography following administration of butorphanol by single IV injection (0.1 to 0.13 mg/kg of body weight) or continuous IV infusion (loading dose, 17.8 microg/kg; infusion dosage, 23.7 microg/kg/h for 24 hours). Pharmacokinetic variables were calculated, and changes in physical examination data, gastrointestinal tract transit time, and behavior were determined over time. RESULTS: A single IV injection of butorphanol was associated with adverse behavioral and gastrointestinal tract effects including ataxia, decreased borborygmi, and decreased defecation. Elimination half-life of butorphanol was brief (44.37 minutes). Adverse gastrointestinal tract effects were less apparent during continuous 24-hour infusion of butorphanol at a dosage that resulted in a mean plasma concentration of 29 ng/ml, compared with effects after a single IV injection. No adverse behavioral effects were observed during or after continuous infusion. CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IV infusion of butorphanol for 24 hours maintained plasma butorphanol concentrations within a range associated with analgesia. Adverse behavioral and gastrointestinal tract effects were minimized during infusion, compared with a single injection of butorphanol. Continuous infusion of butorphanol may be a useful treatment to induce analgesia in horses.

Analgesics, Opioid↗