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The efficacy of a subcutaneous injection of soluble Vitamin B12 in lambs.

AIMS: To assess the efficacy of a soluble Vitamin B12 injection in lambs by measuring changes in the serum and liver Vitamin B12 concentrations. METHODS: Thirty-six lambs were injected subcutaneously with 2 mg of soluble Vitamin B12 while another group of 36 served as untreated controls. Blood and liver biopsy samples for Vitamin B12 determinations were collected just before the injection and at days 1, 2, 5, 8, 16, 24, 30 and 45. RESULTS: The serum Vitamin B12 concentrations of the Vitamin B12 treated lambs increased rapidly compared to the untreated lambs. Concentrations peaked at day 2, decreased rapidly to day 8, and then decreased more slowly until day 24 when there were no longer differences between the groups. Liver Vitamin B12 concentrations of the Vitamin B12 treated lambs were significantly greater over days 8-24. CONCLUSION: A subcutaneous injection of 2 mg of soluble Vitamin B12 was effective in increasing and maintaining the Vitamin B12 status of lambs for about 24 days. CLINICAL SIGNIFICANCE: This Vitamin B12 product is only effective for preventing cobalt deficiency in lambs for about 4 weeks.

Journal Article↗

A comparative biocompatibility study of microspheres based on crosslinked dextran or poly(lactic-co-glycolic)acid after subcutaneous injection in rats.

Microspheres based on methacrylated dextran (dex-MA), dextran derivatized with lactate-hydroxyethyl methacrylate (dex-lactate-HEMA) or derivatized with HEMA (dex-HEMA) were prepared. The microspheres were injected subcutaneously in rats and the effect of the particle size and network characteristics [initial water content and degree of methacrylate substitution (DS)] on the tissue reaction was investigated for 6 weeks. As a control, poly(lactic-co-glycolic)acid (PLGA) microspheres with varying sizes (unsized, smaller than 10 microm, smaller and larger than 20 microm) were injected as well. A mild tissue reaction to the PLGA microspheres was observed, characterized by infiltration of macrophages (MØs) and some granulocytes. Six weeks postinjection, the PLGA microspheres were still present. However, their size was decreased indicating degradation and many spheres had been phagocytosed. The tissue reaction was hardly affected by size differences, except for particles smaller than 10 microm, which induced an extensive tissue reaction. The initial tissue reaction to nondegradable dex-MA microspheres was stronger than towards the PLGA microspheres, but at day 10 the tissue reactions were comparable for both groups. Six weeks postinjection, the dex-MA microspheres were completely phagocytosed, and no signs of degradation were observed. The size and initial water content of dex-MA microspheres hardly affected the tissue response, although less granulocytes were observed for microspheres with higher DS. Slowly degrading dextran microspheres composed of dex-(lactate(1)-)HEMA induced a tissue reaction comparable to the PLGA microspheres. However, degradation of the dex-(lactate(1,3)-)HEMA microspheres was associated with an increased number of MØ's and giant cells, both phagocytosing the microspheres and their degradation products. Similar to PLGA, no adverse reactions were observed for the nondegradable dex-MA and degradable dextran microspheres. This study shows that both nondegradable and degradable dextran-based microspheres are well tolerated after subcutaneous injection in rats, which make them interesting candidates as controlled drug delivery systems.

Animals↗

Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site.

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Absorption↗

Dissociation of insulin absorption and blood flow during massage of a subcutaneous injection site.

Nine healthy volunteers with normal body weights were injected subcutaneously with 125I-labeled soluble human insulin (10 U) in one thigh and 133Xe in the contralateral thigh for the measurement of subcutaneous blood flow on 2 consecutive mornings. On one of the days, standardized massage of both injection sites was performed for 30 min starting 30 min after insulin injection. Serum insulin and plasma glucose were determined intermittently before, during, and after massage, and elimination of radioactivities was monitored continuously by external detectors. During massage, the first-order elimination rate constants of 125I increased approximately sixfold compared with the rise during control (0.19 +/- 0.04 to 0.88 +/- 0.15%/min during the last 15 min of the massage vs. 0.21 +/- 0.03 to 0.32 +/- 0.03%/min during control). Serum insulin increased from 13.8 +/- 1.8 mU/L before massage to a maximal value of 56.4 +/- 8.7 mU/L 10 min after massage (vs. 15.3 +/- 3.0 and 19.7 +/- 2.2 mU/L during control). Plasma glucose fell significantly faster on the massage day, from 10 min after massage onward. No significant alteration in the subcutaneous blood flow was found during or after massage. The results suggest that the pronounced enhancement of insulin absorption induced by massage of the injection site is mainly not blood flow mediated.

Absorption↗

Stimulation of prostaglandin-dependent macrophage suppressor cells by the subcutaneous injection of polyunsaturated fatty acids.

Polyunsaturated fatty acids (PUFAs), in the form of pure linoleic, linolenic, or arachidonic acid, were injected subcutaneously into male C57Bl/6 mice daily for 10 days. Injection of 3.6 mg/day of PUFA resulted in up to a two- to threefold increase in spleen weight. Spleen cell response to mitogens was reduced by about 70%; mixed lymphocyte responses were reduced by about 90% when compared to normal values. In admixture experiments, spleen cells from PUFA treated mice suppressed the mitogen induced blastogenic response of control spleen cells by up to 90%. Fractionation of spleen cells from PUFA treated mice by G-10 adherence resulted in an enrichment of suppressive activity in the adherent cells. The suppressive effect of G-10 adherent cells was abolished by the addition of indomethacin as well as by depletion of macrophages by treatments with agents such as carbonyl iron and leucine methyl ester. These studies indicate that the administration of PUFA has marked immunosuppressive effects in mice. These effects may be related to increased prostaglandin production and appear to be mediated by a macrophage type cell.

Animals↗

Analysis of in vitro lymphoproliferative responses and antibody formation following subcutaneous injection of Actinobacillus actinomycetemcomitans and Wolinella recta in a murine model.

The potential of Wolinella recta and Actinobacillus actinomycetemcomitans to cause abscesses and induce an immune response was tested in BALB/c mice. Mice were injected subcutaneously with W. recta, A. actinomycetemcomitans or a mixture of these 2 microorganisms. Mice injected with A. actinomycetemcomitans alone, or with both organisms, demonstrated abscesses at the injection site 2 days later, from which pure cultures of A. actinomycetemcomitans were isolated. Mice injected with W. recta had small, flat abscesses at the injection site from which no bacteria could be cultured. W. recta was cultured from injection sites only when associated with A. actinomycetemcomitans. Mice developed positive serum IgG antibody responses to W. recta by 20 days post-injection but not to A. actinomycetemcomitans whether injected in pure culture or mixed infection. In vitro lymphoproliferative responses following injection of W. recta and/or A. actinomycetemcomitans resulted in increased lymphocyte reactivity in unstimulated cultures and decreased in vitro responses to phytohemagglutinin. In vitro lymphoproliferative responses to Escherichia coli LPS or Salmonella typhimurium LPS were depressed in mice injected with A. actinomycetemcomitans, but not in mice injected with W. recta.

Abscess↗

Immunolymphoscintigraphy in patients with lymphoma after subcutaneous injection of indium-111-labeled T101 monoclonal antibody.

Indium-111-labeled T101 antibody was injected subcutaneously (s.c.) into the web spaces between the toes of two patients with cutaneous T-cell lymphoma. Computer-assisted gamma scintigraphy was used to measure uptake in lymph nodes and clearance from injection sites. Antibodies passed rapidly and very efficiently from the feet to the inguinal-femoral and iliac lymph nodes after s.c. administration. Contrasting patterns of uptake were seen in patients with different lymph node histology, but additional experience will be required to test the possible correlation with degree of lymph node involvement. This technique provides an efficient, noninvasive method for imaging normal and abnormal lymphoid elements in regional lymph nodes, and it may prove useful in the evaluation of patients with lymphoma or other lymph node disorders.

Antibodies, Monoclonal↗

The relationship of colonic carcinogenesis and hepatic vascular tumors induced by subcutaneously injected-1,2-dimethylhydrazine dihydrochloride in specific pathogen free mice.

1,2-Dimethylhydrazine dihydrochloride (DMH) is one of the most reliable carcinogens for experimental colonic carcinogenesis. In order to evaluate the biological significances of target organ specificity of DMH-induced carcinogenesis, specific pathogen free (SPF) BALB/c mice were injected subcutaneously with DMH for 30 weeks, and were studied pathologically for tumor development of various organs. The data showed that colon tumor developed only at 2% of these mice. However, it produced 100% incidence of malignant endotheliomas and angiosarcomas of blood vessels and these tumors selectively appeared in the liver. There were no overt foci of primary vascular tumors in the heart, lung, kidney, muscle as well as spleen. This tumor model may reveal that the organ specificity of the carcinogenic activity with DMH could be converted, possibly depending upon the bacterial flora in the intestines, and very suitable for the investigation of implications of intestinal bacteria on the colonic and vascular tumorigenesis.

1,2-Dimethylhydrazine↗

Adjuvant and immuno-suppressive effect of six monophthalates in a subcutaneous injection model with BALB/c mice.

The prevalence of allergic airway diseases is rapidly increasing in Western Europe and North America. This increase in disease prevalence may be associated with environmental pollutants. The present study investigated the adjuvant and immuno-suppressive effect of a series of monophthalates which are considered to be important metabolites of commonly used phthalate plasticizers. The effects were studied in a screening model. Ovalbumin (OA), used as the model antigen, was injected subcutaneously in the neck region of BALB/cJ mice with or without one of the test substances, mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBnP), mono-n-octyl phthalate (MnOP), mono-2-ethylhexyl phthalate (MEHP), mono-iso-nonyl phthalate (MiNP) or mono-iso-decyl phthalate (MiDP). The levels of OA-specific IgE, IgG1 and IgG2a in sera were measured by ELISA. Immuno-suppressive effect, defined as a statistically significant reduction in IgE or IgG1 antibody production, was observed with MEHP (1000 microg/ml, IgE and IgG1), MnOP (1000 microg/ml, IgE and IgG1), MiNP (1000 microg/ml, IgE and 10 microg/ml, IgG1) and MiDP (100 microg/ml, IgE and IgG1). Adjuvant effect, defined as a statistically significant increase in IgE or IgG1 antibody level, occurred with MEHP (10 microg/ml, IgE), MnOP (100 microg/ml, and 10 microg/ml, IgG1) and MiNP (100 microg/ml, IgE). No statistically significant immune modulating effect was seen with MBnP and MnBP.

Adjuvants, Immunologic↗

Effects of dimercaprol or thioctic acid on the distribution and excretion of Na374AsO3 injected subcutaneously in rats.

This report dealt with the effects of dimercaprol (BAL) and thiotic acid (TA), antidotes against arsenical, on the distribution and the excretion of 74As in several organs of the rat. Each organ was removed and served for quantitative analysis of 74As five days after subcutaneous injection of Na374AsO3 5 microCi/100 g. Administration of BAL or TA was performed intraperitoneally with a single administration or five consecutive administrations for five days before animals were sacrificed. 74As content in each organ of the rat decreased to a greater extent in the five consecutive administration group of BAL or TA than in the non-treated or single administration groups. Moreover, the excretion of 74As in a digestive tract increased more remarkably in the five consecutive administration group than in the non-treated or single administration groups. There were no differences in the excretion or the content of 74As in each organ between the single administration group and the non-treated group.

Animals↗

Complications of subcutaneous injection ports.

Subcutaneous injection ports have become widely used for patients who require prolonged central venous access. Complications of their placement and use are well documented in the existing literature. We report two previously undocumented complications occurring in Port-a-Cath units, and suggest methods to lessen the likelihood of recurrence of these problems.

Adult↗

Intravenous versus subcutaneous injections of apomorphine in rabbits: a pharmacokinetic paradox.

The objective of this investigation was an attempt to conclusively prove the accidental observation that the AUC of apomorphine in rabbits was repeatedly lower after intravenous injection compared to subcutaneous injection. Apomorphine was administered to rabbits by intravenous and subcutaneous routes at 2 different doses (0.31 mg/kg, n=10; and 0.25 mg/kg, n=6). Plasma drug concentrations were measured by HPLC-ECD and pharmacokinetic parameters were estimated by compartmental and non-compartmental approaches. The AUC of apomorphine in rabbits were: for subcutaneous injection, 14138 +/- 502 ng/ml/min and 12680 +/- 855 ng/ml/min, n=10 and 6, respectively; for intravenous injection, 11850 +/- 718 ng/ml/min and 9147 +/- 671 ng/ml/min, n=10 and 6, respectively. These AUC values were statistically significantly lower when given as intravenous injection compared to subcutaneous injection (p=0.0011 and 0.0117, n=10 and 6, respectively). The T1/2,elim values were: for subcutaneous injection, 17.1 +/- 1.70 min and 18.7 +/- 1.68 min, n=10 and 6, respectively; for intravenous injection, 15.3 +/- 1.20 min and 15.0 +/- 2.24 min, n=10 and 6, respectively. There were no significant differences between the T1/2,elim from both administration routes (p=0.3984 and 0.2158, n=10 and 6, respectively). Given the reproducibility of the results, it was concluded that the AUC of apomorphine after intravenous injection in rabbits is anomalously lower than that of subcutaneous injection.

Animals↗

Identification of the component part in an epoetin alfa preparation that causes pain after subcutaneous injection.

The subcutaneous administration of epoetin alfa preparations may cause pain at the injection site. To identify the pain-causing substance in these formulations we performed two double-blind, placebo-controlled, randomized order, cross-over studies. Differences in pain experienced after subcutaneous injection of an epoetin alfa solution and its vehicle were assessed in 36 patients. The vehicle and its component parts, albumin and citrate, were compared in 36 volunteers. Normal saline served as a placebo control in both studies. Pain scores were obtained from visual analogue pain scales with no divisions and from five point verbal descriptive pain scales. Both the epoetin alfa solution and its vehicle caused significantly more pain than normal saline (P < 0.0001) in the patients studied. In volunteers the pain scores with the vehicle or its citrate component were significantly higher (P < 0.0001) when compared with normal saline or with the albumin component of the vehicle. In conclusion, the local pain experienced after subcutaneous administration of epoetin alfa preparations is mainly caused by the citrate component of the buffered solution. Epoetin alfa and the albumin component of the preparation do not play a role in this phenomenon.

Adolescent↗

Prevention of fatty liver in transition dairy cows by subcutaneous injections of glucagon.

The main objective of this study was to test the extent to which injecting glucagon subcutaneously for 14 d beginning at d 2 postpartum would prevent fatty liver development in transition dairy cows. Twenty-four multiparous Holstein cows were fed 6 kg of cracked corn in addition to their standard diet during the last 30 d of a dry period to induce postpartum development of fatty liver. Glucagon at either 7.5 or 15 mg/d or saline (control) was injected subcutaneously 3 times daily for 14 d beginning at d 2 postpartum. Glucagon at 15 mg/ d prevented liver triacylglycerol accumulation in postpartum dairy cows. Glucagon at 7.5 mg/d showed potential for fatty liver prevention. Glucagon increased concentration of plasma glucose and insulin and decreased plasma nonesterified fatty acid concentrations. No effects of glucagon were detected on plasma beta-hydroxybutyrate concentrations. Glucagon affected neither feed intake nor milk production. Moreover, milk composition was not altered by glucagon. Milk urea N concentrations decreased, and plasma urea N concentrations tended to decrease during glucagon administration, indicating that glucagon may improve protein use. Liver glycogen concentrations were not affected by glucagon. No significant differences in body condition scores were detected among treatments throughout the study. These results indicate that subcutaneous glucagon injections can prevent fatty liver in transition dairy cows without causing major production and metabolite disturbances.

Acetoacetates↗

Interferon kinetics and adverse reactions after intravenous, intramuscular, and subcutaneous injection.

Three groups of six subjects each received a single 36 X 10(6) U dose of recombinant leukocyte A interferon (rIFN-alpha A) as a 40-min infusion, an intramuscular injection, or a subcutaneous injection. Blood samples were collected at specific times after dosing for analysis of rIFN-alpha A serum concentrations by an enzyme immunoassay method, ELISA. The rIFN-alpha A was rapidly distributed and moderately eliminated (t 1/2 = 5.1 hr) after intravenous infusion. The maximum concentrations at the end of intravenous infusion were tenfold the maximum concentrations after intramuscular and subcutaneous injections. Renal tubular secretion or extrarenal elimination was suggested by clearance values of 1.8 times the glomerular filtration rate. After intramuscular and subcutaneous injection, rIFN-alpha A was absorbed slowly (time to reach maximum concentration ranged from 4 to 8 hr), which resulted in prolonged serum concentrations. Estimated bioavailability was more than 80% for both intramuscular and subcutaneous injection shares qualitatively the same adverse reactions, the reactions differ in severity and duration. The adverse effects appear to be related to route of administration of herpes labialis were also noted. There were no significant clinical laboratory abnormalities of medical concern. Although rIFN-alpha A injected by intravenous infusion or intramuscular or subcutaneous injection shares qualitatively the same adverse reactions, the reactions differ in severity and duration. The adverse effects appear to be related to route of administration.

Adult↗

Analgesic duration and kinetics of liposomal bupivacaine after subcutaneous injection in mice.

1. The objective of the present study was to assess the time-course profile of analgesia and bupivacaine concentrations at the site of injection after subcutaneous administration of a single dose of standard bupivacaine or a novel controlled-release liposomal bupivacaine formulation. 2. Groups of mice were injected subcutaneously with 0.2 mL of 0.5% standard bupivacaine or 0.5, 1 or 2% liposomal bupivacaine. 3. A prolonged duration of analgesia occurred in mice receiving liposomal bupivacaine. In the liposomal groups, the bupivacaine remained at the injection site for more than 96 h, compared with approximately 8 h in groups injected with standard bupivacaine. 4. These results confirm that the prolonged analgesia observed after injection of the liposomal formulation is associated with sustained higher levels of bupivacaine at the site of injection.

Analgesia↗

Evaluation of subcutaneous injection of local anesthetic agents as a method of tick removal.

The usefulness of subcutaneous injection of three local anesthetic agents to stimulate tick detachment in an animal model was evaluated. American dog ticks (Dermacentor variabilis) were placed on three New Zealand white rabbits and allowed to attach for 24 hours. Dead and unattached ticks were manually removed. Three local anesthetic agents were studied: 1% lidocaine (group A); 1% lidocaine with epinephrine 1:200,000 (group B); and 1% chloroprocaine (group C). For each group, a total of 0.25 mL of anesthetic agent was injected subcutaneously under the attached portion of each tick, resulting in formation of a 5- to 6-mm wheal. For all three anesthetic agents studied (group A, 34 ticks; group B, 28 ticks; group C, 31 ticks), none of the ticks spontaneously detached within 1 hour after injection. Subcutaneous injection of 1% lidocaine, 1% lidocaine with epinephrine, and 1% chloroprocaine are not effective methods for rapid tick removal in the animal model.

Anesthetics, Local↗

Intradermal injection, as opposed to subcutaneous injection, enhances immunogenicity and suppresses tumorigenicity of tumor cells.

Tumor cell immunogenicity depends heavily upon the microenvironment in which the cells grow. We have compared the tumorigenicity and immunogenicity of the same tumor cells when injected either into the dermis, a tissue containing numerous dendritic cells (DCs), or s.c., at a site which contains only few DCs. After s.c. injection, progressive tumors were constantly obtained, whereas most intradermal injections did not give rise to tumor and immunized animals against additional challenge. We present evidence that the high density of DCs at dermal sites facilitates the capture of tumor antigens and that local inflammation induces maturation of the DCs and their migration into draining lymph nodes.

Adenocarcinoma↗