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PubMed2006

Tissue distribution of endothelial cells in vivo following intravenous injection.

OBJECTIVE: Recent studies have suggested that endothelial cells derived from circulating endothelial progenitors can be used as carriers for cell-based therapy. However, the in vivo homing properties of mature endothelial cells are still unclear. In this paper, we studied the kinetics and specificity of endothelial homing to sites of angiogenesis. METHODS: The kinetics of the distribution of endothelial cells in mice following intravenous injection of 3H-thymidine-labeled microvascular endothelial cells were examined. To detect the homing of viable and apoptotic endothelial cells, GFP-labeled microvascular endothelial cells were injected intravenously in immunodeficient mice. RESULTS: We observed that endothelial cells injected intravenously transit rapidly through the lungs, but do not home specifically to any organ. We did not observe specific accumulation of endothelial cells in subcutaneously implanted tumors following intravenous injection. Rare GFP-labeled endothelial cells were observed in the proximity of tumor blood vessels. However, similar findings were seen when GFP-labeled apoptotic endothelial cells were injected intravenously. CONCLUSION: These findings suggest that integration of mature endothelial cells to the vasculature is a rare event and that engulfment of apoptotic bodies, independent of nuclear fusion, may be misinterpreted as cell plasticity, and care should be taken in the interpretation of such findings.

Animals↗
PubMedDate not supplied

Multifold sonicated dilutions of albumin with fifty percent dextrose improve left ventricular contrast videointensity after intravenous injection in human beings.

An intravenous injection of a onefold dilution of sonicated albumin with 50% dextrose improves echocardiographic left ventricular cavitary opacification in dogs compared with sonicated albumin. The objective of this study was to determine whether sonicated dilutions of albumin with dextrose would improve left ventricular videointensity after intravenous injection in humans and to delineate what ratio of albumin with dextrose results in optimal left ventricular cavitary opacification. We gave intravenous injections (randomized) of sonicated albumin and three different dilutions of albumin with 50% dextrose sonicated at different time intervals (onefold, threefold, and sevenfold dilutions sonicated albumin for 40 seconds and threefold and sevenfold dilutions sonicated albumin for 80 to 100 seconds) to 10 healthy human volunteers. End-diastolic and end-systolic videointensity and mean transit time from the mid-left ventricular cavity were compared after an 8.0 ml intravenous injection of all six samples. The threefold and sevenfold dilutions sonicated for 80 to 100 seconds produced microbubble concentrations similar to those of sonicated albumin but with significantly larger (5.6 microns versus 4.7 microns for sonicated albumin) size. These dilutions produced significantly higher end-diastolic and end-systolic videointensity, area under the time-intensity curve, and mean transit time compared with sonicated albumin or any of the dilutions sonicated for 40 seconds (p < or = 0.005). These data suggest that multifold dilutions of albumin with dextrose produce improved ultrasound contrast.

Adult↗
PubMed1991

[Early phase II study of YM 881 (zinostatin stimalamer) by intravenous injection. Research group for intravenous YM 881].

An early phase II multicentered study of YM 881 (zinostatin stimalamer) was conducted in 36 patients to investigate response and the safety of the drug in malignant tumors. The response could be evaluated in 18 patients, one with brain tumor, 2 with lung cancer, one with breast cancer, one with liver cancer, one with pancreatic cancer, 6 with gastric cancer, and 6 with colon cancer. PR was found in the patient with brain tumor. Major subjective unwanted effects were gastrointestinal symptoms. Objective evidence of hematological changes (thrombocytopenia, decreased hematocrit, and lymphocytopenia) was also obtained.

Adult↗
PubMed1994

Plasma TFPI activity after intravenous injection of pentasaccharide (PS) and unfractionated heparin in rabbits.

Tissue Factor Pathway Inhibitor (TFPI), is known, to be released in plasma after injection of intravenous or subcutaneous injection of heparin or low molecular weight heparin (1,2). Addition of protamine or polybrene in plasma can neutralize anticoagulant effects of heparin in vitro but not completely ex vivo in patients treated with heparin (3). It was believed for many years that this post-heparin anticoagulant effect was due to another activity released by heparin. More recently it has been shown that post-heparin anticoagulant effect could be inhibited by anti-TFPI antibodies (4). Since we have shown in a previous work (5), that in healthy volunteers, pharmacokinetics of TFPI were more closely related to anti IIa activity than anti Xa activity we hypothesized that fragments with anti-IIa activity may be required for this release, possibly from vascular wall. In order to determine if a very low molecular weight glycosaminoglycan can release TFPI in plasma, in the present study, we compared plasma TFPI amidolytic activity after intravenous injection in rabbits of pentasaccharide (PS), a synthetic fragment of very low molecular weight and with a strong and exclusive anti Xa activity, and unfractionated heparin (UFH).

Animals↗
PubMed2001

A role for TGFbeta and B cells in immunologic tolerance after intravenous injection of soluble antigen.

BACKGROUND: Intravenous injection of soluble antigen has been reported to induce immunologic tolerance through a variety of mechanisms including T-cell deletion, anergy, and suppression. To clarify the reported discrepancies, we studied mechanisms of intravenous tolerance to a defined transgenic minor transplantation antigen in mice. METHODS: Wild-type C57BL/6 (B6) mice or congenic B6 B-cell knockout mice were made tolerant to beta-galactosidase (beta-gal). Clinical tolerance was assessed by placement of B6 beta-gal transgenic (tg) and third-party skin grafts. In vitro analysis of T- and B-cell immunity and in vivo treatment with anti-TGFbeta antibodies were used to define mechanisms of induced tolerance. RESULTS: Intravenous injection of beta-gal induced true immunologic tolerance to beta-gal tg skin in wild-type but not in B-cell-deficient recipients, suggesting that antigen presentation by B cells was required for the effect. The tolerogenic manipulation primed a population of CD4+, beta-gal-specific, TGFbeta-producing T cells. Although evidence for both anergy and suppression were observed, subsequent data demonstrated that TGFbeta was a critical immunoregulatory mediator of the tolerant state: neutralizing anti-TGFbeta antibodies fully prevented the induction of tolerance to B6 beta-gal tg skin grafts. Second male beta-gal tg grafts placed onto female recipients that were previously made tolerant to female beta-gal tg skin were rapidly rejected, however, suggesting that this TGFbeta-induced tolerance could not be linked to additional antigenic determinants. CONCLUSIONS: The studies demonstrate a critical role for TGFbeta in mediating tolerance after intravenous injection of antigen but additionally raise concerns about the stability of this tolerant state.

Animals↗
PubMed1998

Intravenous injection of guanylin induces mucus secretion from goblet cells in rat duodenal crypts.

Guanylin, structurally related to the heat-stable enterotoxin of E. coli, is a 15-amino-acid peptide isolated from rat small intestine. We investigated the morphological effects of an intravenous injection of rat and human guanylin upon the rat intestine. Various doses of rat guanylin were injected intravenously in anesthetized rats. After 5, 10 and 30 min, rats were killed by intracardiac perfusion with aldehyde fixative, and specimens of the intestine were then prepared for light and electron microscopy. Intravenously injected rat guanylin rapidly induced mucus secretion from crypt goblet cells in the duodenum. About half of the crypt goblet cells secreted mucous granules by compound exocytosis within 5 min. The villus goblet cells, in contrast, were not sensitive to guanylin. Goblet cells in the jejunum were less responsive than those in the duodenum. This secretory response was rare in the ileum and colon. Human guanylin produced similar results. The mucus secretion induced by guanylin was inhibited by a prior-injection of atropine, but not hexamethonium. Moreover, guanylin induced intense edema in the mucosa and submucosa of the small intestine 5 min after the injection, which disappeared after 30 min. A prior-injection of atropine did not block the appearance of edema. In conclusion, the intravenous injection of guanylin induces two phenomena related to water movement: (1) compound exocytosis of mucous granules from crypt goblet cells in the rat duodenum and jejunum; (2) perineural, inter-epithelial and intra-epithelial edema in the rat small intestine.

Animals↗
PubMed1987

Neurons in the suprachiasmatic area are labelled after intravenous injections of horseradish peroxidase.

Intravenous injections of horseradish peroxidase (HRP) produced labelled neurons in the suprachiasmatic area of house mice (Mus musculus), deer mice (Peromyscus maniculatus bairdi), and white-footed mice (Peromyscus leucopus). In the two species of Peromyscus, a significant proportion of the labelled cells was found within the suprachiasmatic nucleus (SCN). These results suggest that when HRP is injected in the eyes to trace retinal inputs to the hypothalamus, some of the reaction product seen in the SCN may represent blood-borne transport of the enzyme.

Animals↗
PubMedDate not supplied

Distribution of 109Cd in the nervous system of rats after intravenous injection.

The distribution of intravenously injected 109Cd in the nervous system was studied in rats twenty-four hr and one week after the injection. Measurements by gamma scintillation showed a high uptake of cadmium in peripheral sensory and autonomic ganglia whereas the uptake was low in the brain, cerebellum and spinal cord. The accumulation of cadmium in the sciatic nerve was significantly higher than in the brain and spinal nerve roots but lower than in ganglia. Autoradiography confirmed that there was no uptake of cadmium in the major part of the brain parenchyma, but showed an accumulation of the metal in areas outside the blood-brain barrier such as the hypophysis, meninges, choroid plexus and pineal gland. Within the peripheral nervous system, the autoradiography showed a localization of cadmium to dorsal root ganglia and, in addition, an uptake was seen in the connective tissue sheaths surrounding the sciatic nerve. The results indicate that the uptake of cadmium is correlated to regional variations in the permeability of blood vessels. The accumulation of cadmium in certain nervous structures may explain some of the neurotoxicological effects which have been demonstrated in animal experiments.

Animals↗
PubMed2001

Maximizing the benefit--minimizing the risk: the developing role of radiographers in performing intravenous injections.

Performance of intravenous (iv) injections as part of radiographer role development has become fundamental to the operational management of diagnostic imaging departments in the UK. Through discussion of appropriate areas, this review aims to highlight current issues pertaining to iv injection. More importantly, the framework described could be transposed to other existing or future areas of role development. Within a validated system of delegation, utilization of radiographers' skills in an expanded role improves allocation of resources and may increase radiographer motivation and provide career enhancement. Professional body accreditation as well as civil and employment law provide clear guidelines on medicolegal implications, valid consent and accountability. Implementation of an iv administration policy, based on Royal College of Radiologists guidelines, includes proper delegation of duties and safe administration of substances. This should help ensure acceptance of vicarious liability by an employer. Failure to adhere to these established guidelines could leave employers and radiographers vulnerable to medicolegal action. Furthermore, evaluation of radiographer performance, facilitated by clinical governance and departmental audits, should ensure effective and safe practice whilst minimizing associated risks. Evidence-based radiography will provide the necessary drive for future changes in practice as well as further expansion of the radiographer's role.

Clinical Competence↗
PubMed1997

Role of coagulase in a murine model of hematogenous pulmonary infection induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads.

We describe a novel mouse model of acute staphylococcal pneumonia induced by intravenous injection of Staphylococcus aureus enmeshed in agar beads. For comparison, we also used various strains of bacteria, including three strains of S. aureus, two strains of Staphylococcus epidermidis, one strain of Streptococcus pyogenes, three strains of Pseudomonas aeruginosa, and one strain of Klebsiella pneumoniae. All except two strains of S. aureus were cleared rapidly from the lungs. When S. aureus NUMR1 enmeshed in agar beads was injected intravenously, the organisms concentrated and remained in the lung for a period longer than several weeks. Multiple lung abscesses were evident macroscopically, and histological examination of the infected lung showed multiple lung abscesses around the pulmonary arterioles, consisting of bacterial colonies encircled with fibrin filaments and surrounded by inflammatory cells of neutrophils and macrophages. When 14 strains of clinically isolated S. aureus were injected intravenously, the number of bacteria recovered from the lung tissue 7 days after infection correlated with the titer of staphylocoagulase (P < 0.01) but not with the titer of clumping factor. Injection of coagulase-deficient mutant strain DU5843 was associated with a markedly reduced number of viable bacteria isolated from the lung, compared with its coagulase-positive parental strain DU5789. Our results suggest that coagulase may play a role in the development of blood-borne staphylococcal pneumonia in our model. Our animal model is simple and reproducible and resembles blood-borne staphylococcal pneumonia in humans, and it could be useful for investigating the pathogenicity or treatment of staphylococcal pulmonary infection, including infections with methicillin-resistant S. aureus.

Agar↗
PubMed1993

Time course of the distribution of morphine in brain regions, spinal cord and serum following intravenous injection to rats of differing ages.

Previously it was demonstrated that intravenously administered morphine produced greater analgesic but lower hyperthermic responses to morphine in 24-week-old rats in comparison to 8-week-old rats. The differential pharmacological responses to morphine could not solely be attributed to the pharmacokinetic parameters, namely area under the serum morphine concentration-time curve, serum levels of morphine extrapolated to zero time, half-life, mean residence time, apparent volume of distribution at the steady state, terminal rate constant and total body clearance of morphine in serum. In order to determine whether the differences in pharmacological responses to morphine in rats from two age groups are related to differential distribution of morphine in the central nervous system, in the present study, the time course of the distribution of morphine in brain regions (hypothalamus, hippocampus, cortex, pons and medulla, amygdala, midbrain and corpus striatum), spinal cord and serum following intravenous injection of 10 mg/kg dose to 8- and 24-week-old male Sprague-Dawley rats was determined. Morphine injected intravenously produced a greater analgesic but less intense hyperthermic effect in 24-week-old rats in comparison to 8-week-old rats. In most of the brain regions and spinal cord, with few exceptions, the concentration of morphine was found to be greater in 24-week-old rats than in 8-week-old rats. Similarly, the ratio of the concentration of morphine in brain region or spinal cord to serum was significantly higher in rats from the older age group. The studies demonstrate that the altered pharmacological responses to intravenously administered morphine to rats of differing ages may be related to the higher concentration of morphine in the central nervous system of older rats, which in turn may be related to the differences in the blood-brain barrier to morphine in the two age groups.

Aging↗
PubMed1992

Dissolving methohexital in a lipid emulsion reduces pain associated with intravenous injection.

Pain often accompanies intravenous injection of 1% methohexital. The aim of the present study was to test whether pain on injection could be reduced by dissolving methohexital in a lipid emulsion (study A) and whether this would affect anesthetic potency (study B). In study A, 24 healthy volunteers, 36 +/- 1 yr (mean +/- SE), were given 1 ml 1% methohexital in saline, 1 ml 1% methohexital in lipid emulsion, and 5 ml 0.1% methohexital in saline in random order. The injections were given in a small vein in the forearm at 5-min intervals. One minute after each injection, the subject was asked to assess the injection pain on a visual analog scale (0-100 mm). The pain score (median [range]) was 44.5 (0-77) after 1% methohexital in saline, 0.5 (0-26) after 1% methohexital in a lipid emulsion, and 1.0 (0-26) after 0.1% methohexital in saline. The pain score for 1% methohexital in saline was significantly greater than those for the other two solutions (P less than 0.001 for each comparison). In study B, 42 patients, 41 +/- 3 yr, were given 1% methohexital in lipid emulsion (n = 22) or 1% methohexital in saline (n = 20). A bolus of either solution was administered over 10 s, and the patient was considered asleep if there was no gross movement or response to verbal command 40-70 s after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Intravenous injection of adenosine triphosphate for assessing sinus node dysfunction in patients with sick sinus syndrome.

The clinical value of rapid intravenous injection of adenosine triphosphate (ATP, Adephos Kowa # L3, CAS 56-65-5) for assessing sinus node function was examined in 5 patients with sick sinus syndrome (SSS) and 6 normal controls. All patients with SSS showed cardiac pauses longer than 3 s on a 24-h Holter ECG monitoring. First, after prophylactic insertion of a temporary pacemaker in the right ventricle, overdrive suppression test was conducted using the standard technique, and sinus node recovery time (SNRT) was observed to evaluate the sinus node function. Then, 10 min later, 10 mg of ATP was rapidly injected intravenously, and body surface and intracavitary ECG were continuously recorded until the basal state was regained. The rapid injection of ATP resulted in a slight inhibition of sinus node automaticity in normal subjects, but marked inhibition was in patients with SSS associated with suppression of AV conduction. The longest post ATP atrial cycle (AA interval in the intracavitary ECG showed a close inverse relationship with SNRT corrected for basal sinus length (CSNRT), according to the following formula: longest AA interval (ms) = 3.32 x CSRT (ms) +254.4 (r = 0.91, p < 0.001). The results suggest that rapid intravenous injection is a useful tool for the diagnosis of SSS.

Adenosine Triphosphate↗
PubMed1990

Plasma disposition and tolerance of aditoprim in horses after single intravenous injection.

Aditoprim, a broad spectrum antimicrobial agent acting as a reversible dihydrofolate reductase inhibitor, was intravenously injected into four 12 to 24-year old horses at a dosage of 5 mg/kg b. w. Blood samples were collected over a 48-hour period after drug injection, and the separated plasma samples were assayed for aditoprim by high performance liquid chromatography. The body temperature, heart rate, respiration rate, and behaviour were recorded during the experiment. The bilirubin and urea concentrations were also determined in several plasma samples, and liver function tests were carried out. The concentrations of aditoprim in the plasma of horses were higher than the MIC of this drug against recently isolated pathogens for 6-13 h (Pasteurella haemolytica A 1) to 48 h (E. coli). The main pharmacokinetic characteristics of aditoprim in horses were: a large volume of distribution, reaching a mean value of 7.8 l/kg; a mean plasma clearance of 5.0 l/min; a plasma elimination half-life of 12 h. The clinical observations, blood chemistry, and liver function tests all demonstrated that the drug was well tolerated by the horses, although it was injected intravenously as a 25% solution. It was concluded that the 25% aditoprim injection solution could be used in horses without adverse effects at 5 mg/kg. Furthermore, aditoprim should demonstrate good antibacterial effects in horses when intravenously injected once a day.

Animals↗