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Results for “Injections, Subcutaneous”

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PubMed1994

Humoral and cellular immunity to an encoded protein induced by direct DNA injection.

An immunization procedure with naked DNA that generates both humoral and cellular immune responses is described. A mammalian expression vector encoding human factor IX as an example of immunogen was injected into mice three times at 10-day intervals. Three of the 4 mice in which the DNA was injected intramuscularly and 5 of the 9 mice injected subcutaneously produced antibodies to human factor IX. Spleen cells from inoculated mice also showed significant cytotoxic T lymphocyte response to target cells expressing human factor IX. The titers of anti-single-stranded (ss)DNA antibodies were significantly higher in the subsets of genetically inoculated mice than in the control mice, but anti-double-stranded (ds)DNA antibodies were not detected in any serum samples. Thus, intramuscular and subcutaneous injection of plasmid DNA can induce immune responses against the encoded protein without an exposure to virus particles, and this approach may serve as the basis for immunotherapy in the treatment of cancer and infectious diseases in humans.

Animals↗

PubMed2002

Alterations induced by cyclosporine A in myocardial fibers and extracellular matrix in rat.

Cyclosporine A (CsA) is the first choice immunosuppressant universally used in allotransplantation. However, it has been demonstrated that this drug produces unwanted side effects in several organs and in particular in the kidney and in the heart. While the cardiac toxicity, due to alteration of myocardial prostanoid has been reported, no data are available about the effects of CsA on myocardial cytoarchitecture. We studied the CsA induced alterations of the myocardial structure and of the extracellular matrix components (ECM). To test the ECM enzymatic chances we studied a family of enzymes (matrix metalloproteinase-MMP), responsible for the degradation of extracellular matrix components. In particular we investigated MMPI, MMP2 and MMP9. The study was carried out on two groups of Wistar rats. The group I animals served as a control and were injected subcutaneously daily with castor oil for 21 days. Group II: animals were subcutaneously injected daily with CsA (dose: 15 mg/Kg in castor oil) for 21 days. The group I animals (control) had normal heart architecture and low levels of MMPI, MMP2 and MMP9. The group II animals showed degenerative changes with myocardial fibrosis, low levels of MMP1 and MMP9 but a clear increase in MMP2. We suggest that the myocardial fibrosis was a consequence of the cardiotoxic effect of CsA determining the alteration of the balance between synthesis and degradation of ECM. The increase in MMP2 suggests that this enzyme could play a protective role during myocardial damage and represent a compensatory mechanism for the excessive accumulation of collagen.

Animals↗

PubMed1975

[Carcinogenic activity of a 4,4-diaminobiphenyl ester].

4,4'-diaminodiphenyl ether (dadpe) was injected subcutaneously (once a week) or given per orally (1-5 times a week) in rats in a dose of 25 mg/per rat and in mice of line CC57W in a dose of 5 mg/per mouse. Administration of the substance produced in mice and rats under study renal lesions of the nephrosis type with a nephritic component. In later stages of the experiment some rats showed adenomatous regeneration and formation of renal cysts, in one rat hypernephroid cancer of the kidney was observed. Tumors of different localizations were found in 44% of rats (in 7 of 16 animals), and in 57% of mice (in 8 of 14 animals) in experiments with peroral administration of the substance; in 18% of rats (in 7 of 39 animals) and in 33% of mice (in 3 of 9 animals) in experiments with subcutaneous injection of the substance. The results of the experiments have evidenced an insignificant blastomogenic action of 4,4'-diaminodiphenyl ether.

Adenocarcinoma↗

PubMed1986

Effects of cerulein on the normal pancreas and on experimental pancreatic carcinoma in the Syrian golden hamster.

The effects of cerulein on normal pancreas and on N-nitrobis (2-hydroxypropyl) amine (BHP)-induced experimental pancreatic carcinoma in Syrian golden hamsters were studied. Twenty hamsters received a subcutaneous injection of cerulein (20 micrograms/kg). The results showed that when cerulein was injected subcutaneously for 10 days, pancreatic weight and amylase increased. DNA and the pancreatic weight/DNA ratio were also increased significantly in treated hamsters compared with controls (p less than 0.02 versus p less than 0.01). These results indicated that chronic cerulein injection had hypertrophic and hyperplastic effects. DNA synthesis, as measured by histoautoradiography of tritiated thymidine-labeled tissue, increased in pancreatic acinar cells (p less than 0.01) and increased slightly in islet cells and in ductal cells. Tritiated thymidine uptake in the pancreas of the treated group indicated a rather selective exocrine gland incorporation by acinar rather than ductal cells. Sixty hamsters received a subcutaneous injection of BHP (500 mg/kg) once a week, while 63 hamsters received BHP (500 mg/kg) plus cerulein (20 micrograms/kg). Twenty-seven hamsters received cerulein (20 micrograms/kg) alone. All animals were killed from 8 to 27 weeks later, and no cancer-bearing hamsters were observed during the eighth and ninth week following administration. From the 10th to 14th weeks after administration of BHP and cerulein, 87.9% (13 of 15) had tumors compared with 18.7% (3 of 16) after BHP alone (p less than 0.01). One of three and two of 13 tumors were adenoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1986

In search of the subcutaneous-insulin-resistance syndrome.

In numerous patients with diabetes mellitus, a defect in the absorption of subcutaneously injected insulin has been suspected as an explanation for diabetic instability. The common clinical characteristic of these patients is poor metabolic control when insulin is injected subcutaneously, but good metabolic control when the insulin is infused intravenously. We have used three approaches to attempt to identify patients with "subcutaneous-insulin resistance." First, we performed a series of studies of subcutaneous-insulin absorption in 16 patients referred to us with a presumptive diagnosis of resistance to subcutaneous insulin; in none of these patients did we detect an abnormal response of blood glucose levels to insulin administered subcutaneously. Plasma free-insulin levels rose normally after injection. Second, we assayed insulin-degrading activity in subcutaneous biopsy specimens obtained from 25 patients throughout North America and Europe who had been diagnosed as resistant to subcutaneous insulin. In none of these patients did the insulin-degrading activity of subcutaneous tissue exceed the mean value (+/- 2 SD) of eight subcutaneous biopsy specimens obtained from control patients with diabetes. Third, we performed studies of tritiated-insulin absorption in three additional diabetic patients and three control patients with nonbrittle diabetes. These studies also suggested normal absorption of insulin. In none of the patients we studied were we able to confirm the clinical diagnosis of subcutaneous-insulin resistance. We therefore conclude that this syndrome is extremely rare and that misdiagnosis is common.

Absorption↗

PubMed1988

Evaluation of bruises and areas of induration after two techniques of subcutaneous heparin injection.

The subcutaneous administration of the anticoagulant heparin sodium is a frequently performed nursing intervention. Bruising (discoloration) and induration (hardening) occur after some but not all such injections. This has implications for nursing; not only does the patient experience the physical discomfort and the psychologic impact of visible body trauma, but bruising and induration limit possible sites for future injections. Administration technique is frequently cited as a possible cause of bruising and induration. The purpose of this study was to compare two administration techniques currently being used by nurses. Variables studied included syringe size, change of needles after drawing medication into the syringe, use of an air bubble, and type of sponge (dry or alcohol) applied to the site after injection. The sample included 50 medical-surgical patients aged 23 to 88 years. Each subject received two injections by the same investigator using two different techniques. Sites were inspected and bruises and induration measured 52 hours after each injection. To compare the size of bruises and indurations, the data were analyzed by the Mann-Whitney U-Wilcoxon rank sum test, which showed a 0.003 level of significance for bruises and a 0.02 level of significance for induration. To compare the number of subjects in whom bruises and indurations developed, the data were analyzed by the chi-square test, which showed a 0.0458 level of significance for induration but only a 0.1371 level of significance for bruising.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed2000

Inhibition of needlestick-induced simulated viremia by local measures.

BACKGROUND: The possibility of confinement of simulated retrovirus to the inoculation site after needlestick injuries to enhance chances of local intervention and function of lymphaticovenous communications was investigated. METHODS: Using the canine model, technetium-99 m sulfur colloid particles were injected subcutaneously and into the vein and lymphatics. Blood and lymph were collected at a higher level from the femoral vein and the major lymphatic. Flow rates, particle arrival times, concentrations, and other variables were evaluated for 45 minutes by gamma counting. A tourniquet was used to slow dissemination after subcutaneous injection. RESULTS: After subcutaneous inoculation, particles arrived in the blood at 2.81 +/- 0.54 minutes and in the lymph at 6.0 +/- 1.47 minutes. Application of a tourniquet delayed appearance in the blood to 7.11 +/- 1.5 minutes and in the lymph to 40.0 +/- 5.1 minutes. Concentration of particles in lymph was 1,000 times higher than in the blood. Flux values were comparable in both pathways, but accumulation patterns were different. After intravenous injection, particles arrived in lymph at 25.4 +/- 6.44 minutes. After intralymphatic injection particles arrived in the blood within 4 seconds. CONCLUSIONS: There are functional lymphaticovenous communications at the peripheral level. The period between virus inoculation and blood and lymph invasion may be extended by application of a tourniquet; therefore, time could be gained for local intervention.

Animals↗

PubMed2000

Relationship between nociceptor activity, peripheral edema, spinal microglial activation and long-term hyperalgesia induced by formalin.

To determine whether initial nociceptive inputs caused by subcutaneous injection of formalin into the hindpaw are necessary and/or sufficient for allodynic behavior and microglial activation observed at one week following behavior, we examined Sprague-Dawley rats under five test conditions. Test condition 1. Formalin alone group (six rats), 5% formalin was injected subcutaneously into the dorsal side of the right hind paw. Test condition 2. Bupivacaine/Formalin group (six rats), bupivacaine was injected into the ankle area and into the site of formalin injection 10 min before formalin injection. Test condition 3. Saline/Formalin group (six rats), saline was injected 10min before formalin in the same manner as bupivacaine. Test condition 4. Formalin/Bupivacaine group 1 (six rats), bupivacaine was injected 10 min after formalin. Test condition 5. Formalin/Bupivacaine group 2 (six rats), bupivacaine was injected similarly 1h after formalin. The magnitude of paw edema and paw withdrawal thresholds to mechanical stimuli applied to the plantar surface of the injected paw and on the dorsal surface of the contralateral side were evaluated prior to and one week after formalin injection. The lumbar spinal cord was immunohistochemically processed at one week to assess the expression of a marker for activated microglia. The results showed: (i) pre-treatment with bupivacaine blocked both phases of formalin-evoked pain behaviors and the mechanical allodynia that developed one week post-formalin injection, but did not block microglial activation; (ii) treatment with bupivacaine 1h after formalin injection reduced paw edema and prevented skin ulceration, but one week allodynia and microglial activation were still present; and (iii) prolonged spinal microglial activation was not dependent on acute formalin-induced nociceptor activity, but was strongly associated with the amount of tissue destruction. Our studies suggest that: (i) the central sensitization associated with the phase II of formalin-evoked behaviors and spinal microglial activation are both necessary to permit the development of the long-term hyperalgesia produced by the subcutaneous administration of formalin into the rat's hindpaw; and (ii) acute nociceptive inputs following formalin injection are not necessary for central microglial activation that may be triggered by nerve damage or prolonged signals from peripherally inflamed tissue

Anesthetics, Local↗

PubMed1986

Local subcutaneous atrophy after corticosteroid injection.

Subcutaneous atrophy developed in a 36-year-old woman at the site of a triamcinolone acetonide (Kenalog) injection for subdeltoid bursitis. Occurrence of local atrophy after corticosteroid injection is relatively frequent yet unappreciated. It is more common in young women and girls who are given preparations with a lesser degree of water solubility. Although the condition is often reversible, instances of long-term disfigurement are well documented. This complication of a useful treatment method can be avoided by following a set of precautions for local injection of corticosteroids.

Adrenal Cortex Hormones↗

PubMed1983

Cell-mediated immunity in F 344 rats bearing intraocular tumors derived from human adenovirus 12-induced retinal tumor.

The eyes of 10 F344 rats were inoculated with retinal tumor cells (EXP-5 cell line) induced by human adenovirus 12. The animals were killed at 4 weeks thereafter, and the cytotoxicity of their lymphocytes was investigated by using 51Cr-releasing assay. The percentage of EXP-5 cells killed in vitro by lymphocytes was higher in 10 rats with ocular tumors (24.6% +/- 6.1%, mean +/- SD) than in 10 control rats (6.2% +/- 1.8%). Morphologic investigation using syngeneic spleen cells confirmed the presence of lymphoid cells, resembling T-lymphocytes, adhering to EXP-5 cells. The influence of subcutaneous injection of EXP-5 cells on the growth of intravitreously injected tumor cells was investigated. Cells injected subcutaneously prior to intravitreous injection elicited an immune response that was capable of controlling vitreous tumor growth. These findings suggest that the rats with transplanted retinal tumors develop a cell-mediated immune response in the early stage of tumor bearing, and that a state of pre-existing specific immunity can overcome so-called "immunologic privilege" of the vitreous body.

Adenoviruses, Human↗

PubMed1989

Peripheral pharmacokinetics of apomorphine in humans.

Apomorphine, a potent dopamine agonist, has been used in acute and chronic studies of parkinsonism and other neurological disorders. To define its peripheral pharmacokinetics, we administered apomorphine by subcutaneous injection, by subcutaneous infusion, and by intravenous infusion to 15 patients with parkinsonism and measured plasma apomorphine levels by high-performance liquid chromatography with electrochemical detection. The peak drug levels and area under the curve were closely correlated with the dose administered; time to peak was brief and was independent of dose. The variation in absorption was high between subjects but low within individual subjects. In 11 of 15 subjects, the disappearance of drug could be described by a two-compartment model, with a distribution half-life of 5 minutes and an elimination half-life of 33 minutes. The drug absorption, volume of distribution, plasma clearance, and half-lives were similar for subcutaneous injection, subcutaneous infusion, and intravenous infusion. We conclude that apomorphine is rapidly and completely absorbed from subcutaneous tissue, correlating with the rapid onset of clinical effects, and that the brief duration of clinical action of the drug is explained by its rapid clearance.

Adult↗

PubMed1982

Development of a transplantable model of pancreatic duct adenocarcinoma.

We report here the first development of a continuous cell line in tissue culture of an animal pancreatic duct adenocarcinoma that is histologically similar to human pancreatic duct adenocarcinoma. A primary pancreatic duct adenocarcinoma, induced in a male Syrian golden hamster after 23 weeks of weekly subcutaneous injection of N-nitrobis (2-hydroxypropyl)amine, was minced and injected subcutaneously into three hamsters. After 8 weeks, a single tumor was apparent. Subsequent passages of fragments into the cheek pouches were performed at 3- to 4-week intervals. After five passages, minced fragments of a tumor were placed in tissue culture. Colonies appeared by 7 days; an epitheloid cell line, without fibroblasts, was established by 60 days. Single-cell suspensions, injected into hamster cheek pouches or subcutaneously, produced tumors in a dose-dependent fashion. Spent culture medium of tissue culture cells and saline extracts of freshly excised tumors contained pancreatic oncofetal antigen-like activity.

Adenocarcinoma↗

PubMed1994

Studies of the distribution and functional roles of transitory amoeboid microglial cells in developing rat brain using exogenous horseradish peroxidase as a marker.

When HRP was injected intraperitoneally (i. p.), labelled amoeboid microglial cells (AMC) were consistently localized in the subcortical white matter and circumventricular zones in early postnatal (1 and 7 days old) but absent in late postnatal (14-day-old) rats. The ingested HRP disappeared from the labelled cells 5 days after IP injection. Subcutaneous injection of HRP had also resulted in the labelling of amoeboid microglial cells in the corpus callosum of early postnatal rats. When the injected HRP was followed ultrastructurally over a time course sequence in intravenously (i. v.) injected rats, it was first detected in the invaginations on the luminal side of endothelium and in the endothelial cytoplasm 30 min after injection. HRP was present both in the endothelium and amoeboid microglial cells 3 hours later. With time, the tracer was progressively accumulated in the cytoplasm of AMC and it was sequestered in the vacuoles and lysosomes. It is concluded from this study that when injected i. p., i. v. or subcutaneously in the early postnatal rats, HRP is circulated to the blood vessels in the subcortical white matter and circumventricular zones where it gains access into the nervous tissues by transendothelial transport. The extravasated tracer is then phagocytosed by the residential AMC and subsequently degraded. The absence of labelling of AMC is attributed to the maturation of BBB which impedes the entry of exogenous tracer by the 14th postnatal day.

Aging↗

PubMed2005

Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid lipid nanoparticles in Dalton's lymphoma tumor bearing mice.

The study evaluates the capability of tripalmitin nanoparticles in enhancing the tumor uptake of etoposide, and the influence of administration route on the biodistribution and tumor uptake of etoposide loaded tripalmitin (ETPL) nanoparticles in Dalton's lymphoma tumor bearing mice. ETPL nanoparticles were prepared by melt-emulsification and high pressure homogenization followed by the spray drying of nanodispersion. Characterization of the nanoparticles was done by particle size analysis, zeta potential measurement and scanning electron microscopy. The size of ETPL nanoparticles was 387 nm and possessed negative charge. Etoposide and ETPL nanoparticles were radiolabeled with 99mTc with high labeling efficiency. The labeled complexes showed good in vitro stability in the presence of DTPA/cysteine and serum stability. Etoposide and ETPL nanoparticles were injected by subcutaneous, intravenous or intraperitoneal routes and their biodistribution and tumor uptake were determined. Subcutaneous injection reduced the distribution of ETPL nanoparticles to all the tissues studied whereas after intraperitoneal injection, the distribution of ETPL nanoparticles to tissues was higher than free etoposide. The intravenous injection resulted in lower concentrations of ETPL nanoparticles in the organs of RES compared to free etoposide. ETPL nanoparticles experienced significantly high brain distribution after intraperitoneal injection indicating its potential use in targeting etoposide to brain tumors. After subcutaneous injection, the tissue distribution of ETPL nanoparticles increased with time indicating their accumulation at the injection site for a longer time. The tumor uptake of both etoposide and ETPL nanoparticles was significantly high after subcutaneous injection (P<0.001) compared to the other routes of administration. The tumor concentration of ETPL nanoparticles after subcutaneous injection was 59 folds higher than that obtained after intravenous and 8 folds higher than after intraperitoneal route at 24 h post-injection. The tumor concentration of ETPL nanoparticles increased with time after subcutaneous injection indicating the slower and progressive penetration from the injection site into the tumor. The study signifies the advantage of incorporating etoposide into tripalmitin nanoparticles in controlling its biodistribution and enhancing the tumor uptake by several folds. The study also reveals that, of the three routes investigated, subcutaneous injection is the route of preference for facilitating high tumor uptake and retention and is likely to have greater antitumor effect resulting in tumor regression.

Animals↗

PubMed2006

Effects of postnatal exposure to methamphetamine on the development of the rat retina.

Since the development of different cell types in the retina occurs at different rates, it is possible that exposure to an exogenous substance may produce effects during one time period, but not during another. This study aims to analyze the effects of methamphetamine (METH) in the growth pattern of an experimental model as well as neurochemical and immunohistochemical parameters of the dopaminergic system of the rat retina. The three development stages chosen in this study are key markers in rat eye development. Rats were given 15 mg/kg body weight per day of METH as subcutaneous injections in 0.9% saline (3 mL/kg weight/day) from the day after birth PND 1 to PND 6, PND 13, and PND 29. Each daily dose was split into two. The control group was injected subcutaneously with saline. Both the schedule and volume for injecting saline in the control group were the same as for the METH-treated group. There were no significant differences in the total number of offspring per litter among treatment groups. All offspring had similar body weight at birth. Analysis of body weight on PND 1, showed that animals treated with METH had similar body weights to control-treated animals and females had smaller weights than males. For growth evolution, only litters with a sex ratio of four males and four females were used. Animals treated with METH had smaller body weights than the control-treated animals for all ages studied (PND 7, 14, and 30). Within the control group at PND 30, a significant difference was found in the body weight of females, which was lower when compared with males. For the postnatal model, 7 deaths occurred for the METH-exposed group. No deaths occurred in the control group in a total of 16 saline-injected litters comprising 186 pups. Although the levels of dopamine (DA) was within normal values for the postnatally exposed METH group when compared with its respective control group at PND 7 and 30, at PND 14 this was not the case: in this experimental group, the level of DA was lower than in the control group for both females and males. Support for this result was not evident from the TH immunoreactivity studies, probably because the methodology lacks the sensitivity to distinguish any mild effects, such as that observed in the postnatal model at PND 14. The level of the DA metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) remained unaffected at all ages studied, for both females and males. The results obtained in this study support the view that, during the critical periods in which the catecholamines can influence the development of neurones, METH transiently affects the pattern of the dopaminergic system in the developing retina.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1976

Amelioration of insulin lipoatrophy by dexamethasone injection.

Widespread subcutaneous lipoatrophy occurred in a 47-year-old woman after subcutaneous injections of isophane insulin suspension for five months. Subsequent systemic treatment with a dexamethasone (0.08 mg/day) insulin mixture injected subcutaneously into the depressed areas resulted in an impressive return of subcutaneous tissue after eight months of continuous therapy.

Dexamethasone↗

PubMed1978

Acute toxic effects of chaetoglobosin A, a new cytochalasan compound produced by Chaetomium globosum, on mice and rats.

A new cytochalasan compound, chaetoglobosin A produced by Chaetomium globosum, was studied for its toxicity to animals. By subcutaneous injection, 2 mg/kg body weight of chaetoglobosin A killed young Wistar rats acutely, and in the mouse of DDD strain, LD50 values of chaetoglobosin A were estimated 6.5 and 17.8 mg/kg for male and female, respectively. By oral administration, 400 mg/kg of chaetoglobosin A caused little adverse effect on mice and rats. Pathological examination of the mice, injected subcutaneously with 5 mg/kg of the toxin, revealed marked edema at the injection site which appeared in several hours after injection and subsided in a week. In other tissues necrosis of the thymus and spleen and degeneration of the spermatocytes in the testicles were noticeable. With characteristic cytotoxic effects like cytochalasin B, chaetoglobosin A is an interesting mycotoxin, although it may be of little significance as a food- or feed-borne toxin.

Animals↗

PubMed1991

Administration of heparin by subcutaneous infusion with a programmable pump.

Heparin has a short half-life (8 to 12 hours) and therefore must be administered by continuous infusion or by intermittent subcutaneous injection. Intermittent subcutaneous injection may lead to fluctuation in the levels of anticoagulation attained. In correcting this deficiency, the programmable automated subcutaneous infusion pump in conjunction with weekly home nursing visits has been used. Eight pregnant women with documented deep venous thrombosis or embolic events before pregnancy who received such therapy were studied. Eight similar subjects who received intermittent subcutaneous injection, matched for age, parity, site of deep venous thrombosis, and days on a regimen of heparin therapy, served as the control group. The mean daily dose of heparin by subcutaneous infusion pump was higher (29,445 vs 13,822 U), resulting in smoother, more therapeutic heparinization (mean partial thromboplastin time, 20.6 vs 10.4 seconds above control) when compared with the intermittent subcutaneous injection group (p less than 0.05, p less than 0.007). There were two complications (hematoma, site infection) in the intermittent subcutaneous injection group while none occurred in the subcutaneous infusion pump group. When used in concert with weekly home visits, the subcutaneous infusion pump method of administration allowed more even control of anticoagulation, appeared to result in fewer complications (although not statistically significant), and subjectively was better received by patients than the intermittent subcutaneous injection technique.

Adult↗