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Encapsulation of interleukin-2 in murine erythrocytes and subsequent deposition in mice receiving a subcutaneous injection.

Radiolabeled recombinant human interleukin-2 (IL-2) was successfully encapsulated in both mouse and sheep erythrocytes. Of the added IL-2, 70% was recovered bound to or encapsulated within the carrier cells. Erythrocytes containing IL-2 were stable in vitro and most of the IL-2 remained associated with the cells following a 16-h incubation at 37 degrees C. When carrier erythrocytes containing IL-2 were injected subcutaneously into mice, intact [35S]IL-2 was detectable in a number of tissues 3 days after injection.

Animals↗

[Subcutaneous injection of fatty tissue pearls--experimental study and clinical applications].

In 20 female adult rats, fatty tissue of 0.6 or 1.2 g was taken from each side of the pelvis. One fatty block, after being cut into pearls of about 2 mm in diameter, was injected subcutaneously to the left side of the back while another was transplanted en bloc in the right side. The rats were randomized into four groups and samples of fat were taken at 3, 6, 12 and 24 weeks. After 24 weeks, the sample from left side was found to be 21.1% of its original weight while the right side was only 6.9% (P < 0.05). In clinical practice, subcutaneous fat was sucked out from submandibular or abdominal regions, cut into pearls of 2-3 mm in diameter and injected to depressed area, such as glabella or naso-labial grooves. The procedure was applied to 27 sites of 15 cases. Follow-up of 6 months showed satisfactory results in 51.9%, acceptable in 18.5% and no effect in 29.6%.

Adipose Tissue↗

Retention of bacterial lipopolysaccharide at the site of subcutaneous injection.

The tissue distribution of Klebsiella pneumoniae O3 lipopolysaccharide (KO3 LPS) was studied in mice injected subcutaneously (s.c.) or intraperitoneally (i.p.) with 125I-labeled KO3 LPS. Marked retention of KO3 LPS radioactivity could be found at the site of s.c. injection for several weeks. On the other hand, about 85% of the radioactivity rapidly disappeared from the peritoneal cavity within 6 h after i.p. injection. The long-term presence of KO3 LPS at the injection site was also supported by experiments with 51Cr-labeled KO3 LPS and immunoblotting and immunofluorescence staining methods. The R-form LPS lacking the O-specific polysaccharide chain of KO3 LPS and the lipid A fraction of KO3 LPS seemed to remain at the site in larger amounts and for longer times than KO3 LPS. There were no marked differences in the retention pattern at the injection site among KO3 LPS, Escherichia coli LPS, Salmonella typhosa LPS, and Salmonella enteritidis LPS. However, much less radioactivity accumulated in the livers and spleens of mice injected with either KO3 LPS or S. typhosa LPS compared with the other LPS preparations. It was suggested that retention of LPS at the site of s.c. injection may play an important role in the development of various biological actions of s.c. injected LPS.

Animals↗

Resistance of mice to infection with Friend disease virus after subcutaneous injection of Friend virus and Friend spleen cells.

Swiss mice injected subcutaneously with suspensions of spleen cells or an extract of spleens from mice infected with Friend virus develop resistance to subsequent intravenous inoculation of Friend virus. A single injection of either Friend virus or Friend cells induces resistance. Immunized mice display resistance when challenged 6 months after immunization and survive for at least 20 weeks after infection. Neutralization tests indicate that serum, but not lymphoid cells of resistant animals, can neutralize Friend virus. In vitro neutralization tests indicate that residence of virus within the peritoneal cavity of immune mice for 1 h sharply reduces the infective titer of the virus.

Animals↗

Six month administration of gelified intranasal insulin in 16 type 1 diabetic patients under multiple injections: efficacy vs subcutaneous injections and local tolerance.

OBJECTIVE: Nasal insulin administration is a potential route for intensive insulin management, less invasive and more rapid than subcutaneous injections. Previous studies have shown poor bioavailability (less than 15%) with nasal insulin administration with various absorption enhancers. The aim of the study was to evaluate in type 1 diabetic patients, the metabolic efficacy and local tolerance of a new gelified sprayed nasal insulin containing glychocolate and methylcellulose as absorption promoters. MATERIAL AND METHODS: The study was conducted in 16 type 1 diabetic patients (HbA1c 8.6+/-0.2%) in a cross-over trial including 2 six month randomized periods: a) NPH twice daily + 3 pre-prandial nasal insulin doses + nasal supplementation in case of unexpected hyperglycaemia; b) NPH twice daily + 3 pre-prandial regular insulin injections. End points were HbA1c levels, hypoglycaemic episodes and tolerance evaluated at month 0, 2, 6 and 8 on clinical symptoms and objective nasal assessments. RESULTS: Four patients were withdrawn because of nasal burning (3 cases) and persistent sinusitis (1 case), and one patient had purulent sinusitis at the month 6 examination. At month 6, HbA1c levels were comparable (8.3 +/- 0.1 vs 8.6 +/- 0.1%, m +/- SEM, NS) for nasal and subcutaneous period respectively. The number of hypoglycaemic events was identical during the 2 periods (88 episodes). Nasal tolerance with the gelified form was better than with the already reported lyophilized form but, when present, symptoms were more marked, suggesting a potentiating additional role of methylcellulose excipient on nasal intolerance. CONCLUSIONS: 1) Gelified nasal insulin is as efficient as subcutaneous regular insulin in type 1 diabetic patients. 2) Other galenic forms should be investigated to improve nasal tolerance and bioavailability.

Administration, Intranasal↗

Methods for mitigating soft-tissue injury after subcutaneous injection of water soluble contrast media.

RATIONALE AND OBJECTIVES: Water soluble contrast media may cause tissue injury by extravasation during intravenous injection during various radiologic examinations. The authors attempted to find out what kind of management could mitigate tissue injury when extravasation of water soluble contrast media occurs. METHODS: Sodium and meglumine ioxithalamate was injected subcutaneously into 240 hind feet of 120 rats that were divided into six groups according to the methods of experimental management. Experimental managements included the following: no further management (control), injection of distilled water, injection of normal saline, injection of hydrocortisone, hot water application, and cold water application. Gross morphologic changes in each group were compared with those in the control group. RESULTS: Only the saline injection group showed statistically significant decrease of tissue injury compared with the control group. CONCLUSIONS: Saline injection lessens the degree of soft-tissue injury at contrast media extravasation sites in rats.

Animals↗

Antigen-pulsed CD8alpha+ dendritic cells generate an immune response after subcutaneous injection without homing to the draining lymph node.

Two subsets of murine splenic dendritic cells, derived from distinct precursors, can be distinguished by surface expression of CD8alpha homodimers. The functions of the two subsets remain controversial, although it has been suggested that the lymphoid-derived (CD8alpha+) subset induces tolerance, whereas the myeloid-derived (CD8alpha-) subset has been shown to prime naive T cells and to generate memory responses. To study their capacity to prime or tolerize naive CD4(+) T cells in vivo, purified CD8alpha+ or CD8alpha- dendritic cells were injected subcutaneously into normal mice. In contrast to CD8alpha- dendritic cells, the CD8alpha+ fraction failed to traffic to the draining lymph node and did not generate responses to intravenous peptide. However, after in vitro pulsing with peptide, strong in vivo T cell responses to purified CD8alpha+ dendritic cells could be detected. Such responses may have been initiated via transfer of peptide-major histocompatibility complex complexes to migratory host CD8alpha- dendritic cells after injection. These data suggest that correlation of T helper cell type 1 (Th1) and Th2 priming with injection of CD8alpha+ and CD8alpha- dendritic cells, respectively, may not result from direct T cell activation by lymphoid versus myeloid dendritic cells, but rather from indirect modification of the response to immunogenic CD8alpha- dendritic cells by CD8alpha+ dendritic cells.

Animals↗

Absorption of heparin, LMW heparin and SP54 after subcutaneous injection, assessed by competitive binding assay.

Unfractionated heparin, pentosan polysulphate (SP54) and the low molecular weight heparins CY216 and CY222 were injected subcutaneously at a minimum of weekly intervals into 5 healthy volunteers. The dose was 75 mg in all cases. Concentrations of administered glycosaminoglycan in serial plasma samples and voidings of urine were measured using a competitive binding assay, and biological activity was assessed in plasma using APTT and anti-Xa clotting assays. There was wide individual variation in the absorption of unfractionated heparin as indicated both by the maximal plasma concentrations reached 2-3 h after injection and by the area under the concentration vs. time curve. The efficiency of absorption increased and the individual variation decreased with decreasing molecular weight of the administered glycosaminoglycan. Urinary excretion correlated with plasma concentration, and recovery in the urine also increased with decreasing molecular weight. Similar patterns of uptake and clearance were indicated by the APTT and competitive binding assays, but anti-Xa clotting activity could be detected in the plasma after clearance of the administered glycosaminoglycan.

Absorption↗

Nitroxynil. Anthelmintic activity in cattle following subcutaneous injection.

Nitroxynil injected subcutaneously at 10 mg/kg live mass achieved Class A efficacy when evaluated by the non parametric method against adult Fasciola gigantica. Haemonchus placei, Bonustomum phlebotomum and Oesophagostomum radiatum in cattle. The compound was not effective against adult Cooperia spp. at the same dosage.

Ancylostomatoidea↗

Di-(2-ethylhexyl) phthalate possesses an adjuvant effect in a subcutaneous injection model with BALB/c mice.

The prevalence of allergic airway diseases is rapidly increasing in Western Europe and North America and the introduction of anthropogenic chemicals may explain a part of this increase. Recently, our group found that degradation products from several commonly used phthalate plasticizers possess adjuvant activity in an animal model. Mono-2-ethylhexyl phthalate, which is the degradation product of di-(2-ethylhexyl) phthalate (DEHP), was among these substances. These findings prompted the study of the adjuvant activity of the parent compound itself. Thus, DEHP was studied in a model using ovalbumin (OA) as the model antigen. OA was injected subcutaneously in the neck region of BALB/cJ mice with or without DEHP. The levels of OA-specific IgE, IgG1 and IgG2a antibodies in sera were measured by ELISA. Adjuvant effect, defined as a statistically significant increase in antibody level, was observed with IgG1 at a concentration of 2000 microg DEHP/ml after both one and two boosters.

Adjuvants, Immunologic↗

Effect of thiamine on the excretion of subcutaneously injected lead in rats.

The effect of thiamine on the excretion of lead in feces was investigated using rats injected subcutaneously with lead acetate and thiamine pyrophosphate. The amount of lead excreted increased with the amounts of thiamine administered, while lead concentrations in blood, liver and femur also increased. The amount of lead excreted in feces decreased, however, with administration of oxythiamine and vanadium. These results suggest that excretion of lead in feces is enhanced by thiamine and that it promotes evacuation of lead from the body.

Animals↗

Circulating levels of melatonin following its oral administration or subcutaneous injection in sheep and goats.

The effect of differing doses and routes of administration of melatonin on plasma melatonin levels in sheep and goats has been examined. Melatonin injected subcutaneously in a saline or oil vehicle caused high transitory peaks in plasma melatonin whereas oral administration, in either saline solution or adsorbed onto pelleted foodstuff, resulted in sustained elevated blood levels for periods exceeding 7 h. Oral dosages of about 2 mg proved adequate to raise the normal daytime plasma levels in both sheep and goats to levels within the normal night-time range. It was concluded that with ruminants the oral route of administration provides a convenient and practical way of administering melatonin for physiological study.

Administration, Oral↗

Response of dogs to subcutaneous injections of various concentrations of propylene glycol with water.

Each of 85 dogs was injected, subcutaneously, with 5 different mixtures of propylene glycol (PG) and aqueous vehicles. Each dog was observed for immediate (within 15 minutes) and delayed (at 24, 48, and 72 hours) reactions. The reactions were classified as none, mild, moderate, and severe for the different observation periods. The study indicated that a mixture containing between 20% and 50% PG caused the fewest immediate reactions and that the number of delayed reactions increased as the proportion of PG in the solutions increased. Viscosity of the mixture also should be considered when selecting a vehicle.

Animals↗

Percutaneous computed tomography lymphography in the rabbit by subcutaneously injected nanoparticulates.

RATIONALE AND OBJECTIVES: Surgical lymphangiography is infrequently used in staging cancer because of its inherent limitations. Radiopaque nanoparticulates target lymph nodes draining interstitial tissues and could make percutaneous lymphography feasible. METHODS: Experimental nanoparticulate contrast agent formulations were injected subcutaneously in the forepaw or hindpaw of normal rabbits or rabbits with induced reactive nodal hyperplasia. Axillary and popliteal nodes were imaged with thin-section computed tomography (CT) using quantitative methods to measure node enhancement. Dose-response (0.1-2.0 ml) and time course (4 hr to 10 weeks) of enhancement were assessed. RESULTS: Nodal enhancement above 100 Hounsfield units was consistently obtained. Enhancement was significantly related to dose and peaked at 10 hr with slow washout over the observation period. Nodes with reactive hyperplasia were larger and had heterogeneous enhancement patterns distinctly different from normal nodes. CONCLUSION: Percutaneous CT lymphography effectively depicts the macroscopic intranodal architecture in rabbits.

Animals↗

The effects of the subcutaneous injection of the crude venom of the Australian common brown snake, Pseudonaja textilis on the skeletal neuromuscular system.

1 The effects of the crude venom of the Australian common brown snake on the mammalian neuromuscular system have been investigated. 2 The venom was injected subcutaneously into the dorso-lateral aspect of one hind limb of the rat. The limb was paralyzed within 90 min and remained paralysed for 2 to 3 days. 3 The exposed muscles failed to respond to indirect excitation, and individual fibres were not depolarized at the nerve-muscle junction by exposure to carbachol. 4 The wet weight, histological appearance, resting potential and input resistance of the muscle fibres and their ability to generate directly elicited action potentials were unaffected by exposure to the venom. 5 Administration of venom to isolated preparations caused a reduction in the amplitude of miniature endplate potentials, with no change in frequency. The quantal content of evoked endplate potentials was unchanged. 6 It was concluded that the crude venom was largely devoid of presynaptic activity and myotoxicity, and that its primary site of neurotoxicity was directed to the postsynaptic membrane.

Action Potentials↗

Subcutaneous injection of monoclonal antibody 96.5. Biokinetics in the nude rat heterotransplanted with malignant melanoma.

Nude rats heterotransplanted with human melanoma metastasis were injected subcutaneously on the hind paw with 125I-labelled monoclonal antibody 96.5 and with control antibody 131I-OKT3. The elimination from the injection site followed a biexponential function. The uptake in the inguinal lymph nodes on the side of the injection was initially high, but after 90 h it equalled the control side. The uptake in the tumour was slower than after i.v. injection but higher than in other tissues except blood. More than 80% of the activity in the dissected liver represented circulating blood. The uptake ratio of 96.5/OKT3 was c.3 in the tumours but c. 1 in all other tissues including blood. The capillary filtration coefficient was proportional to the uptake in organs like liver, lungs and muscle. It is concluded that subcutaneously injected radiolabelled monoclonal antibodies are initially transported via the lymph but then mainly distributed via the blood reaching the different tissues including tumours.

Animals↗

Adjuvant effect of di-n-butyl-, di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate in a subcutaneous injection model using BALB/c mice.

During the last decades, the prevalence of the allergic airway diseases, asthma and rhinitis, has increased world-wide. Introduction of environmental chemicals with adjuvant effect may play a role in this increase. In the present study, the adjuvant effects of di-n-butyl-, di-n-octyl-, di-iso-nonyl- and di-iso-decyl phthalate are studied in a screening model. Ovalbumin, used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with the selected phthalate in concentrations from 2-2000 microg/ml. Additionally, the mice were boosted once or twice with ovalbumin alone. Immunization with ovalbumin alone, the ovalbumin control group, served as the baseline for antibody production, whereas aluminium hydroxide served as the positive control. The levels of ovalbumin-specific IgE, IgG1 and IgG2a antibodies in sera were determined. Adjuvant effect was accepted to be present if a statistical increase in antibody production occurred in a test group as compared to an ovalbumin control group together with the fulfillment of dose-response relationships. Adjuvant effect varied strongly between the phthalates investigated. Phthalates with 8 or 9 carbon atoms in the alkyl side chains were the stronger adjuvants whereas phthalates with shorter or longer alkyl side chains possessed less adjuvant activity. Adjuvant effects were apparent either from the IgE or the IgG1 response or both, whereas no effect was seen on the IgG2a response. Additional studies with airborne exposure are required to establish whether the hazards also result in a significant risk for the development of allergy in man.

Adjuvants, Immunologic↗