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At least 19 recordsLinked to original sources
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↗
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↗
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↗
PubMed1989

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↗
PubMed1986

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↗
PubMed1978

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↗
PubMed1990

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1992

Subcutaneous injection of oral cyclosporin A solution.

Cyclosporin A (CyA) is the agent of choice for immunosuppression in the majority of rodent organ and tissue allotransplantation experiments. Subcutaneous injection of suitably dissolved pure CyA powder preparation is the acceptable standard of drug administration. We investigated the possibility of using oral CyA solution in an injectable form and compared its availability with that of the standard solution in a rat model. Oral CyA solution diluted in placebo (olive oil) and standard solution prepared from pure compound were injected subcutaneously at a dose of 5 mg/kg/day to two groups of rats. Trough whole blood CyA concentrations were measured on day 10 following initiation of treatment. Blood CyA levels of the standard solution group (1,167 +/- 246 micrograms/liter, mean +/- SD) were virtually identical to those of the oral solution group (1,105 +/- 179 micrograms/liter; P greater than 0.05). In addition, the oral solution was easier to prepare and caused less injection site morbidity than the standard solution. We conclude that placebo-diluted oral CyA solution may be safely injected subcutaneously to rats and results in consistent blood levels, comparable to those achieved with standard solution prepared from pure compound.

Administration, Oral↗
PubMed1979

Absorption kinetics of subcutaneously injected insulin. Evidence for degradation at the injection site.

The absorption of subcutaneously injected insulin was examined by injecting semisynthetic [3H] insulin in anaesthetized pigs and subsequently analysing the tissue excised from the injection site. Contrary to previously accepted views, a significant proportion of insulin was degraded at the injection site. The disappearance of intact [3H] insulin from the injection site followed a monoexponential function with a half-time of 59 min.

Absorption↗
PubMed1989

Radionuclide venography of lower limbs by subcutaneous injection: comparison with venography by intravenous injection.

We have proved that subcutaneous injection (SC) of a small dose of Tc-99m pertechnetate (1 to 2 mCi: 37 to 74 MBq) at acupuncture points (K-3 and B-60) may offer an alternative method of radionuclide venography (RNV) of the lower limbs. In this study, we compared intravenous (IV) RNV and SC-RNV in 22 consecutive cases with typical signs and symptoms suggesting venous abnormality of the lower limb(s) from March to May 1988. They are 11 male and 11 female, aged 47.7 +/- 15.7 years. Among the 44 limbs of the 22 cases, 4 were normal, 12 (27.3%) were found to have varicose veins in the legs only, 18 (40.9%) had partial stenosis of the deep veins (14 poplito-tibial and 4 superficial femoral), and 13 (29.6%) had complete stenosis of the deep veins (4 poplitotibial, 1 superficial femoral and 8 ilio-femoral. SC-RNV showed almost the same results as IV-RNV in 21 (47.7%), superior to IV-RNV in 22 (50%) (including 4.6% failure of IV-RNV), and inferior to IV-RNV in 1 (2.3%). We conclude that SC-RNV is definitely an alternative method of lower-limb venography. Since it is in most cases superior to IV-RNV, we suggest that it can take the place of IV-RNV in routine work.

Acupuncture Points↗
PubMed1987

[Subcutaneous injection of spleen cells from mice bearing large methylcholanthrene-induced sarcoma enhances subcutaneous tumors and artificial pulmonary metastases].

To examine the effect of spleen cell on host antitumor immunity, spleen cells from mice bearing large Methylcholanthrene-induced sarcoma (MCA-F) (F4w spc) were injected subcutaneously into mice which had been inoculated subcutaneously with MCA-F cells or intravenously with the subline from MCA-F cells which had high potential of metastasis (FLn2). F4w spc enhanced significantly the growth of subcutaneous MCA-F tumor in a dose-dependent fashion (p less than 0.05) and increased the number of metastatic lesions induced by intravenous FLn2, but not spleen cells from normal mice or spleen cells from mice bearing MCA-D tumor which is antigenically different from MCA-F. These results suggest that spleen cells of mice bearing a large tumor have a component suppressing specifically antitumor immunity. In this study, effects of spleen cells were assessed by the subcutaneous injection into tumor bearing mice instead of Winn's assay, and this method was thought to be useful for analysis of effector cells in tumor immunity.

Animals↗