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At least 19 recordsLinked to original sources
PubMed2002

Pharmacokinetics of fluconazole in loggerhead sea turtles (Caretta caretta) after single intravenous and subcutaneous injections, and multiple subcutaneous injections.

Superficial and systemic mycotic infections are common among clinically ill sea turtles, which places growing importance on the establishment of pharmacokinetic-based dosage regimens for antifungal drugs. The pharmacokinetic properties of the antifungal drug fluconazole, after intravenous (i.v.) and subcutaneous (s.c.) injections, were studied in juvenile loggerhead sea turtles (Caretta caretta) housed at 23.0-26.5 degrees C. Fluconazole pharmacokinetic properties were further assessed in a multiple-dose s.c. regimen derived from the pharmacokinetic parameters determined in the single-dose study. Pharmacokinetic parameters were calculated, using a two-compartment model, from plasma concentration-time data obtained after single i.v. and s.c. administrations of fluconazole at a dosage of 2.5 mg/ kg body weight in six juvenile sea turtles. Blood samples were collected at intervals through 120 hr after each dose, and the concentration of fluconazole in plasma was measured by reverse-phase high-performance liquid chromatography. The i.v. and s.c. elimination half-lives were 139.5 +/- 36.0 and 132.6 +/- 48.7 hr (mean +/- SD), respectively. Systemic clearance of fluconazole was 8.2 +/- 4.3 ml/kg x hr, and the apparent volume of distribution at steady state was 1.38 +/- 0.29 L/kg. A multiple-dose regimen was derived, which consisted of a loading dose of 21 mg/kg body weight and subsequent doses of 10 mg/kg administered through s.c. injection every 120 hr (5 days). This regimen was administered to four juvenile sea turtles for 10 days, and blood samples were taken to determine peak and trough plasma concentrations of fluconazole. The mean concentrations for the two peak concentrations were 16.9 +/- 1.1 and 19.1 +/- 2.8 microg/ml 4 hr after dosing, and the mean concentrations for the three trough concentrations were 7.2 +/- 2.2, 10.4 +/- 2.7, and 10.7 +/- 2.9 microg/ml 120 hr after dosing. The terminal half-life after the last dose was calculated at 143 hr. Throughout the multiple dosing, fluconazole concentrations remained above approximately 8 microg/ml, a concentration targeted when treating mycotic infections in humans. The results of this study suggest that fluconazole can be effectively administered to sea turtles at a dosage of 10 mg/kg every 5 days after a loading dose of 21 mg/kg.

Animals↗
PubMed1989

Enhanced bioavailability of subcutaneously injected insulin coadministered with collagen in rats and humans.

The present study was undertaken to develop an agent that stabilizes insulin injected subcutaneously. 125I-Porcine insulin with 0.2 U/kg unlabeled porcine insulin was subcutaneously injected with or without collagen in the rat under the depilated skin of the back. At various times, the radioactivity in subcutaneous tissue was assayed for insulin and its metabolites by gel filtration. The degradation and absorption rate constants of insulin at the subcutaneous injection site were estimated according to a one-compartment model. The degradation rate constant of insulin in the presence of collagen at the injection site was less than half of the control rate. The inhibition was confirmed by increases in the immunoreactive insulin plasma levels and the hypoglycemic effect in rats and healthy volunteers. We postulate that collagen prevents insulin from being degraded by inhibiting proteolytic enzymes, mainly collagenase-like peptidase, in subcutaneous tissue.

Animals↗
PubMed1983

The production of carcinomas in vivo by the intravenous or subcutaneous injection of a hepatocellular tumour cell line.

Suspensions of cells of an aflatoxin-induced hepatocellular carcinoma cell line, which grow rapidly as tumours when injected subcutaneously into nude mice, have been injected subcutaneously and also intravenously via the hepatic portal or tail vein into syngeneic host animals. Efficiency of the injections was checked histologically and histochemically in parallel experimental animals. Subcutaneous injections consistently resulted in the appearance of solid tumours at the site of injection within 1 month. However, despite the apparent importance of the establishment of a blood supply when tumours are grown subcutaneously, only a low incidence of tumours (less than 20%) was detected in animals receiving intravenous injections. These results suggest that the proposed use of injection of liver cell suspensions into the portal tract as a sensitive means of detecting transformation may only be of limited value.

Acyltransferases↗
PubMed1998

Effect of subcutaneous injection of granulocyte-macrophage colony stimulating factor (GM-CSF) on healing of chronic refractory wounds.

OBJECTIVE: To assess the effect of granulocyte macrophage colony-stimulating factor (GM-CSF) on healing of chronic wounds. DESIGN: Prospective open study. SETTING: 1 cancer hospital and 2 University hospitals, Pakistan. SUBJECTS: 35 patients with chronic wounds (duration 3 months or longer) that had not responded to standard treatment. Patients with malignant ulcers were excluded. INTERVENTION: GM-CSF 10 microg/cm2 was injected subcutaneously along the edges and base of the wound. The treatment was given only once and patients were followed weekly for a minimum of six weeks. MAIN OUTCOME MEASURES: Changes in size, shape, depth, edges and base of the wound, amount and quality of the granulation tissue, and type of discharge. RESULTS: Six patients were excluded from the analysis, 4 who died early of underlying disease and were not evaluable, and 2 who were excluded when histological examination of the wound showed that it was malignant. Although various types of wounds were studied, most (n = 10, 34%) were postoperative. 23 of the wounds were over 2 cm in diameter (mean 4.8 x 4.6 cm) with thin granulation tissue, and almost half were infected. Nine of the 29 wounds healed completely within six weeks while another 11 decreased in size by more than 50%; 7 patients responded slightly. Only two wounds showed no evidence of healing during the observation period. More than half of the 20 wounds that responded had healed by three weeks. Response did not correlate with any clinical variable including the presence of infection. Toxicity was negligible. CONCLUSIONS: We conclude that subcutaneous injection of a single dose of GM-CSF may induce healing in refractory chronic wounds. Trials are necessary to validate these initial observations and to decide the optimal dose and route, and whether any additional benefit may be derived from repeated injections.

Analysis of Variance↗
PubMed1998

Low molecular weight silicones are widely distributed after a single subcutaneous injection in mice.

To examine the distribution of low molecular weight silicones in body organs, separate groups of female CD-1 mice were injected with either breast implant distillate composed primarily of hexamethylcyclotrisiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, and tetradecamethylcycloheptasiloxane or a polydimethylsiloxane oil containing low molecular weight linear siloxanes. Mice were injected subcutaneously in the suprascapular area and killed at different times. Levels of individual low molecular weight silicones were measured in 10 different organs (brain, heart, kidney, liver, lung, mesenteric lymph nodes, ovaries, spleen, skeletal muscle, and uterus). In mice treated with the cyclosiloxane mixture and killed at 3, 6, or 9 weeks, highest levels of cyclosiloxanes were found in the mesenteric lymph nodes, ovaries, and uterus, but all organs examined contained cyclosiloxanes. In a cohort killed at 1 year, most organs contained measurable cyclosiloxanes with highest levels in mesenteric lymph nodes, abdominal fat, and ovaries. Of the individual cyclosiloxanes measured, selective retention of decamethylcyclopentasiloxane and dodecamethylcyclohexasiloxane relative to octamethylcyclotetrasiloxane was seen in all organs at all time points studied. Organs from animals receiving the linear siloxane mixture were harvested at 9, 12, and 15 weeks. We found maximum levels in the brain, lungs, and mesenteric lymph nodes, but all other organs contained measurable levels. These data are, to the best of our knowledge, the first demonstration that after a single subcutaneous injection silicones are widely distributed throughout the body and can persist over an extended period.

Animals↗
PubMed2002

[Subcutaneous injection of plasmid VEGF gene: a method of gene therapy to enhance the viability of random skin flap].

OBJECTIVE: Gene therapy has been becoming one of the most attractive medical areas. But the using of gene therapy in plastic surgery is relatively scarce. Our purpose was to investigate the effect of naked plasmid encoding Vascular Endothelial Growth Factor on the viability of the random skin flap by directly injected subcutaneously. METHODS: 30 female Sprague-Dawley rats randomly divided into three groups. A random dorsal skin flap of 3 cm x 9 cm was elevated in each of the rats. And 1 ml double-distilled water solution was injected subcutaneously, which was only water in group 1 during the operation, 200 micrograms VEGF cDNA plasmid in group 2 during the operation, 200 micrograms pcDNA3.1/zeo(+)--VEGF in group 3, 24 hours before the operation, respectively. 7 days after the operation, all the animals were sacrificed by overdose anesthetic. The survival tissue was measured with planimetry. Two samples were harvested from each group for pathological check and immunohistochemical test. RESULTS: Immunohistochemical staining demonstrated that there was human VEGF deposited around the capillary in the flaps treated with VEGF gene. The flaps treated with VEGF gene had a larger percentage of survival skin (group 1 = 47% +/- 5.4%, group 2 = 65.4% +/- 6.3%, group 3 = 72.3% +/- 8.5%, P < 0.05). CONCLUSION: VEGF gene directly injected into subcutaneous can express VEGF. It makes the gene therapy simple and practical and will be promising future in the tissue transplantation.

Animals↗
PubMed2005

Pharmacokinetics of an oral drug (acetaminophen) administered at various times in relation to subcutaneous injection of exenatide (exendin-4) in healthy subjects.

Exenatide is an incretin mimetic with potential glucoregulatory activity in type 2 diabetes. This randomized, single-blind, placebo-controlled 6-way crossover study assessed exenatide's effect on acetaminophen pharmacokinetics. Of 40 randomized healthy subjects, 39 completed the study. On the placebo day, acetaminophen (1000 mg) was ingested and placebo injected subcutaneously at 0 hours. On exenatide days, acetaminophen was ingested at -1, 0, +1, +2, and +4 hours, relative to the 10 mug exenatide injected subcutaneously at 0 hours. With exenatide injection, mean plasma acetaminophen AUC(0-12 h) values were reduced by 11% to 24% (vs placebo). Peak plasma acetaminophen concentrations were similar for the -1-hour and placebo groups and reduced by 37% to 56% at other times. The most frequent adverse events were generally mild to moderate nausea and vomiting. Exenatide treatment concurrent with or preceding acetaminophen ingestion slowed acetaminophen absorption but had minimal effect on the extent of absorption.

Acetaminophen↗
PubMed2004

Local vascular access of radioprotein injected subcutaneously in healthy subjects and patients with breast cancer-related lymphedema.

UNLABELLED: The aim of the study was to use dual-isotope lymphoscintigraphy in healthy volunteers and women with breast cancer-related lymphedema (BCRL) to detect and quantify transport of radiolabeled protein from a subcutaneous injection depot to local blood vessels as a potential mechanism of protection against edema resulting from treatment to the axilla. METHODS: A total of 29 subjects and 18 women with a history of BCRL received bilateral subcutaneous injections of human IgG (HIgG) in the second dorsal web space of each hand, (99m)Tc-HIgG on one side and (111)In-HIgG on the other. In 8 further healthy subjects, epinephrine was administered with the labeled HIgG. Radioactivity at each depot was measured at regular intervals for a total of 3 h using a collimated sodium iodide scintillation detector, and radioactivity in venous blood sampled from both arms was measured using an automatic sample counter. Ipsilateral blood time-concentration curves were corrected for recirculating activity by subtraction of the simultaneous contralateral concentration, to define the component of ipsilateral blood resulting from local vascular access of radioprotein. Accumulation of activity in blood was expressed in relation to injected activity and activity that had left the depot and was calculated as a function of time-in systemic blood, by multiplying contralateral concentrations by an estimate of the subject's blood volume, and in ipsilateral blood, by using indicator dilution theory and an assumed forearm blood flow of 20 mL/min. RESULTS: (99m)Tc-HIgG and (111)In-HIgG behave almost identically with respect to depot clearance and accumulation in contralateral venous blood, with or without epinephrine, which reduced both depot clearance and blood accumulation rate. Moreover, a side-to-side correlation with respect to contralateral accumulation was present in healthy subjects, was not abolished by epinephrine, and was maintained in the face of asymmetric accumulation in BCRL. Contralateral accumulation of radioprotein was reduced in BCRL after injection into the affected side only when the hand was involved. In contrast to contralateral sampling, ipsilateral time-concentration and accumulation profiles were consistent with instability of (111)In-HIgG and rapid local vascular access of small amounts of protein-free (111)In. Experiments based on precipitation of protein with trichloroacetic acid confirmed relatively high levels of unbound ipsilateral (111)In, especially in samples obtained early after injection. Substantial accumulation of protein-bound (99m)Tc was observed in ipsilateral blood, with a time course similar to that of contralateral accumulation. Positive correlation between ipsilateral and contralateral blood (99m)Tc activity was observed at all time points, often significantly, in contrast to (111)In, for which it was negative at all time points. Ipsilateral accumulation of (99m)Tc adjusted for activity that had left the depot was unchanged with respect to the affected arm in BCRL patients. CONCLUSION: Whereas (111)In-HIgG and (99m)Tc-HigG are interchangeable for measurement of depot clearance and contralateral venous accumulation rates, ipsilateral sampling is much more sensitive to protein-free radionuclide and detects significant differences resulting from some instability of (111)In-HIgG. On the basis of (99m)Tc data, there appears to be substantial local vascular access of radioprotein within the arm, both in healthy subjects and in patients with BCRL, through either lymphaticovenous communications or direct transendothelial transport.

Arm↗
PubMed1980

Platelets, fibroblasts, and inflammation: tissue reactions to platelets injected subcutaneously.

Evidence from the literature indicates that platelets contain (besides mediators of acute inflammation) factors capable of stimulating fibroblastic growth: namely, serotonin and "platelet factors" demonstrable by their effect on tissue cultures of fibroblasts. The purpose of this study was to find out whether an inflammatory and a fibroblast-stimulating effect could be demonstrated in vivo, in the rat, using a single subcutaneous injection of concentrated platelets (platelet pellet). For comparison, rat brain, heart, and kidney tissue were homogenized under sterile conditions, spun down, and injected subcutaneously. Platelet pellets caused intense edema and neutrophil infiltration; after 8 days they had assumed a spherical shape and were surrounded by typical myofibroblasts. The 30 pellets of tissue homogenates induced a much milder acute inflammatory reaction; only one (a heart pellet) induced a recognizable myofibroblast reaction. The delayed appearance of myofibroblasts around platelet pellets was probably mediated by the neutrophils, which accumulated in large amounts around platelet pellets. Using this in vivo model, a direct fibroblast-stimulating effect of platelets was not demonstrable. It is pointed out that there are analogies between cellular reactions induced by injected platelet pellets and by intravascular platelet thrombi.

Animals↗
PubMed1991

The effect of subcutaneous injection site on absorption of human growth hormone: abdomen versus thigh.

OBJECTIVES: To investigate whether growth hormone (GH) absorption is site dependent. DESIGN AND MEASUREMENTS: Human growth hormone (hGH, Norditropin) 4 IU, was injected subcutaneously on two separate occasions: into the thigh on one occasion and into the abdomen on a second occasion. Blood was sampled for GH, insulin, glucose, non-esterified fatty acids and glycerol at baseline and hourly for 12 hours. Serum insulin-like growth factor I was measured at baseline, and after 12 and 24 hours. SUBJECTS: Eleven healthy young adults (8 M, 3 F). RESULTS: Following the injection serum GH had risen by 1 hour and peaked by 3-6 hours. The peak GH and growth hormone area under the curve were significantly higher after injection in the abdomen compared with the thigh (GH peak (mean +/- SEM) 103 +/- 20 vs 41 +/- 8 mU/l, P = 0.002 and GH area 528 +/- 86 vs 239 +/- 34 mU/l h, P = 0.003 respectively). Serum insulin-like growth factor I at 12 and at 24 hours showed a significant rise from the baseline level, but no significant difference was observed between the two injection sites. No significant difference in plasma insulin, glucose, non-esterified fatty acids or glycerol was observed between the two methods of injection. CONCLUSION: Subcutaneously injected GH is better absorbed from the abdominal site than from the thigh.

Abdomen↗
PubMed1977

Tumours in mice after subcutaneous injection of automobile exhaust condensates.

Automobile exhaust condensate (AEC), either mixed with benzo[a]pyrene (BaP) or suspended or dissolved in tricaprylin, was injected subcutaneously into NMRI mice in a series of experiments. The addition of AEC decreased the incidence of tumours which developed with 30, 90 and 270 microgram BaP. Reduction of tumour incidence was proportional to the amount of AEC added. With an injection of 10 microgram BaP, the latent period was greatly increased when AEC was added, but the occurrence of tumours was the same. Components of AEC appear to inactivate BaP, at least temporarily. In further experiments AEC and nine fractions thereof were injected subcutaneously into mice. The fraction comprising only polycyclic aromatic hydrocarbons (PAH) induced the highest incidence of tumours. In contrast, when it was administered in combination with other fractions the PAH fraction was less active. Application of the products of further fractionation of PAH showed that polycyclic compounds with seven or more rings can also induce tumours in this model.

Animals↗
PubMed1976

Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection.

Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.

Calcium↗
PubMed1992

Subcutaneous injection of factor IX for the treatment of haemophilia B.

Haemophilia B patients are normally treated, either prophylactically or in response to bleeding episodes, by frequent intravenous injections of factor IX purified from blood donors. Here we show in model animal experiments that purified human factor IX, when injected subcutaneously, is rapidly (in 3-11 h) and reasonably efficiently (30-40% of an equivalent intravenous dose) transported at least partly by the lymphatic drainage of the skin into the bloodstream, mostly in a biologically active form. This suggests that patients could be treated prophylactically by subcutaneous rather than intravenous injection, where the short delay in raising plasma factor IX to haemostatic levels would be clinically acceptable. More generally, our studies emphasize that the subcutaneous route of injection should be useful for other therapeutic proteins, including other clotting factors, which have to be delivered to the bloodstream, as long as their half-life is at least a few hours allowing time for transport into the general circulation.

Animals↗
PubMed1970

Migration of asbestos fibres from subcutaneous injection sites in mice.

Crocidolite asbestos fibres, suspended in physiological saline, were injected subcutaneously into one or both flanks of 95 CBA/Lac female mice; 75 control mice received injections of saline only. Most animals were killed at chosen intervals of between 2 and 42 days after injection but some were left for longer periods of up to 623 days. At autopsy, many lymphoid and non-lymphoid structures were removed and examined for the presence of asbestos by the following techniques: haematoxylin and eosin staining followed by conventional and polarized light microscopy; Perl's stain; microincineration followed by phase-contrast microscopy; maceration with KOH followed by phase-contrast microscopy; and electron microscopy.A combination of haematoxylin and eosin staining and microincineration was found to be the most convenient and reliable method for demonstrating asbestos fibres in the tissues. Electron microscopy was essential for detecting very small fibres and for locating them to specific intracellular structures.The morphological findings indicate that some migration of asbestos fibres away from the initial site of injection takes place. Dissemination is usually along lymphatic pathways and fibres tend to accumulate in the lymphoid tissues, particularly in the regional (axillary) lymph nodes; smaller amounts were found in inguinal, mediastinal and lumbar nodes. The fibres were usually intracellular, lying inside the phagosomes of macrophages, but larger fibres weresometimes encountered lying free. Small numbers of fibres were seen in the spleen and also in non-lymphoid organs such as the liver, kidneys and brain-suggesting that some asbestos may enter the blood stream. There was no evidence of massive or selective spread to subserosal tissues in the thorax or abdomen, though trapping of asbestos fibres was observed in pleural "milky spots" in long-term survivors. The possible role of milky spots in the development of pleural plaques and mesotheliomata is discussed.

Animals↗
PubMed1990

Experimental tissue damage after subcutaneous injection of water soluble contrast media.

Various water soluble contrast media (WSCM) were injected subcutaneously into 970 hind feet of 485 rats. Gross morphologic changes were seen after the injection and analyzed as a function of various physicochemical characteristics of WSCM. The WSCM of larger volume, higher osmolality, higher iodine content, and meglumine salts rather than sodium salts caused more severe tissue damage; younger rats showed more severe tissue damage by WSCM of high osmolality.

Animals↗
PubMed2000

Five fold increase of insulin concentration delays the absorption of subcutaneously injected human insulin suspensions in pigs.

Human NPH U100 (100 IU/ml), given once daily, is often absorbed too fast to cover the basal insulin demand throughout 24 h. The aim of the present study was to examine whether the absorption of human insulin suspensions would be delayed by increasing the insulin concentration from U100 to U500. In each experiment 10 IU of corresponding human Ul00 and U500 preparations, labelled with 125I-insulin, were injected subcutaneously and contralaterally in the neck of a pig followed by monitoring residual radioactivity over the injection sites. The time until 75, 50 and 25% residual radioactivity (T(75%), T(50%) and T(25%)) using NPH U500 was compared with NPH U100 in 14 experiments: T(75%): 5.0+/-0.5 (mean+/-SEM) vs 3.8+/-0.3 h (P=0.007, paired t-test), T(50%): 12. 2+/-0.9 vs 9.0+/-0.6 h (P=0.003) and T(25%). 24.2+/-1.2 vs 17.9+/-1. 2 h (P=0.001). The corresponding values for semilente U500 compared with semilente U100 in eight experiments were: T(75%): 2.8+/-0.4 vs 1.6+/-0.2 h (P=0.02), T(50%): 5.6+/-0.6 vs 3.4+/-0.3 h (P=0.01) and T(25%): 10.9+/-1.1 vs 7.2+/-0.7 h (P=0.009). Thus, the absorption of a given dose of human NPH or human semilente insulin in pigs is substantially delayed by changing the insulin concentration from Ul00 to U500. Human NPH U500 appears to be more appropriate than human NPH U100 for injection once daily in basal insulin therapy.

Absorption↗
PubMed2001

Pancreatic exocrine damage induced by subcutaneous injection of a low dosage of zinc.

The aim of this study was to observe whether a low dosage of zinc induced mouse pancreatic injury. Dosages of zinc from 0.1 to 50 mg/kg were injected subcutaneously in mice, and plasma and pancreatic clinical parameters were observed 3-24 h after the injection. Plasma alpha-amylase activity increased 10 and 24 h after the injection of 25 or 50 mg/kg of zinc, whereas pancreatic alpha-amylase activity decreased 3 h after more than 5 mg/kg of zinc was injected. The activity recovered after 24 h except in the group injected with 50 mg/kg of zinc. The plasma glucose level did not change when less than 25 mg/kg of zinc was injected. The pancreatic zinc contents increased 3 h after more than 1 mg/kg of zinc was injected. The pancreatic metallothionein (MT) contents increased 6 h after the injection of 1 mg/kg of zinc. In addition, when more than 5 mg/kg of zinc was injected, the MT content increased at 3 h. In histochemical observations, cell damages such as fibrosis and necrosis were observed in pancreatic exocrine cells, but not in cells of Langerhans islets. From the present study, a single injection of a low dosage of zinc induces injury in pancreatic exocrine cells, but not endocrine cells.

Animals↗