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PubMed1963

YELLOW FEVER VACCINATION IN MALAYA BY SUBCUTANEOUS INJECTION AND MULTIPLE PUNCTURE. HAEMAGGLUTININ-INHIBITING ANTIBODY RESPONSES IN PERSONS WITH AND WITHOUT PRE-EXISTING ANTIBODY.

In view of the risk of introduction of yellow fever into South-East Asia, comparative studies have been made of yellow fever vaccination in Malayan volunteers with a high prevalence of antibody to related viruses and in volunteers without related antibody. In a previous paper the neutralizing antibody responses of these volunteers were reported. The present paper describes the haemagglutinin-inhibiting (HI) antibody responses of the same groups of volunteers and discusses the relationship of these responses to the neutralizing antibody responses.The HI responses to yellow fever following vaccination closely paralleled the neutralizing antibody responses whether vaccination was subcutaneous or by multiple puncture. Volunteers with a high level of YF HI antibody due to infection with other group B viruses were found to be less likely to show a significant YF HI response than those without antibody. 90% of HI responses could be detected by the 21st day after vaccination.As with neutralizing antibody responses, volunteers given vaccine doses of 50-500 mouse intracerebral LD(50) subcutaneously gave greater responses than those given higher doses.

Animals↗
PubMed1982

Further studies of the polysaccharide of Klebsiella pneumoniae possessing strong adjuvanticity. III. Augmentation of the antibody response to subcutaneously injected sheep red blood cells by the adjuvant polysaccharide.

The adjuvant action of the O3 antigen of Klebsiella (KO3) on the antibody response to sheep red blood cells (SRBC) was elucidated by injecting both KO3 and SRBC subcutaneously at the right inguinal region of SMA mice. We demonstrated that KO3 exhibits a novel ability to augment anti-SRBC plaque-forming cell responses in both the local lymph node and the spleen at a relatively late stage of immunization. Escherichia coli lipopolysaccharide, dextran sulfate and concanavalin A showed such an action only minimally. In parallel with the development of the adjuvant action, KO3 definitely activated B cells in the local lymph node polyclonally for either IgM or IgG synthesis, suggesting that the mechanism of the adjuvant action includes direct stimulation of B cells by KO3 at the late stage. Neither increase in trapping of lymphocytes in the local lymph node nor change in tissue distribution of antigen was shown to be primarily involved in the mechanism of the adjuvant action.

Adjuvants, Immunologic↗
PubMed1994

Alkalisation of lignocaine-adrenaline reduces the amount of pain during subcutaneous injection of local anaesthetic.

A double blind, randomised controlled trial was performed to compare the amount of pain experienced after subcutaneous infiltration of lignocaine with adrenaline, and the same anaesthetic buffered to pH 7.1-7.3, in patients undergoing liposuction (n = 8), blepharoplasty (n = 7), mammaplasty (n = 6), and in volunteers (n = 10). A linear analogue pain scale was used to access pain. In all four groups the buffered solution caused significantly less pain (p < 0.001 except for mammaplasty--p = 0.02).

Adult↗
PubMed2006

Inhalation of human insulin is associated with improved insulin action compared with subcutaneous injection and endogenous secretion in dogs.

This study compared the effects of endogenous (portal) insulin secretion versus peripheral insulin administration with subcutaneous or inhaled human insulin [INH; Exubera, insulin human (rDNA origin) inhalation powder] on glucose disposal in fasted dogs. In the control group, glucose was infused into the portal vein (Endo; n = 6). In two other groups, glucose was infused portally, whereas insulin was administered peripherally by inhalation (n = 13) or s.c. injection (n = 6) with somatostatin and basal glucagon. In the Endo group, over the first 3 h, the arterial insulin concentration was twice that of the peripheral groups, whereas hepatic sinusoidal insulin levels were half as much. Although net hepatic glucose uptake was greatest in the Endo group, the peripheral groups demonstrated larger increases in nonhepatic glucose uptake so that total glucose disposal was greater in the latter groups. Compared with s.c. insulin action, glucose excursions were smaller and shorter, and insulin action was at least twice as great after INH. Thus, at the glucose dose and insulin levels chosen, peripheral insulin delivery was associated with greater whole-body glucose disposal than endogenous (portal) insulin secretion. INH administration resulted in increased insulin sensitivity in nonhepatic but not in hepatic tissues compared with s.c. delivery.

Administration, Inhalation↗
PubMedDate not supplied

Hepatocellular necrosis associated with the subcutaneous injection of an intranasal Bordetella bronchiseptica-canine parainfluenza vaccine.

A three-year-old wire fox terrier inadvertently was given an intranasal Bordetella bronchiseptica and canine parainfluenza vaccine subcutaneously. The dog subsequently developed both a local inflammatory reaction at the injection site and acute, nonseptic hepatocellular degeneration and necrosis. The patient was treated successfully with intravenous fluids and amikacin. Two months after the injection, the serum bile acid concentrations and hepatic histopathology indicated the presence of continued hepatocellular disease.

Administration, Intranasal↗
PubMed2006

Granulomas induced by subcutaneous injection of leuprorelin acetate.

Leuprorelin acetate, a chemotherapeutic agent used to treat prostate cancer, is a synthetic luteinizing hormone-releasing hormone (LHRH) agonist. We report a 75-year-old man who presented with several large subcutaneous nodules at the site of leuprorelin acetate injections for his prostatic cancer. A biopsy of the nodules disclosed epithelioid granulomatous inflammation and resulted in a diagnosis of drug-induced granulomatous reaction to leuprorelin acetate.

Abdomen↗
PubMed1983

Developmental toxic effect after subcutaneous injections of methadone in Charles River CD-1 mice.

Four groups of Charles River CD-1 pregnant mouse dams were dosed subcutaneously daily with 5, 10, 20, and 28 mg/kg of methadone during day 6 to 15 of gestation. Prenatal and postnatal studies were conducted in the offspring and mouse dams. Caesarean sections were performed on some of the females from each group on day 19 of gestation and fetuses evaluated by routine teratologic methods. All females remaining were allowed to deliver, and several postnatal signs were recorded from the pups during the lactation period. Maternal mean body weight gains and food consumption were reduced. No apparent alteration in the food efficiency index was detected, thus maternal malnutrition may not have been a factor in producing adverse effects on offspring. The incidence of external and visceral malformations was neither dose-related nor significantly different from those of the controls. However, administration of methadone decreased ossification of the digits, sternum, and skull of the offspring. Adverse effects of methadone on reproduction were apparent at doses of 20 mg/kg/day and above, and characterized by an increase in resorptions and a decrease in the number of live fetuses per litter. Methadone was found not to be teratogenic to the CD-1 mice. However, adverse effects on intrauterine growth, fetal ossification, neonatal growth, development, and survival rate were seen among weaned pups.

Animals↗
PubMed1985

Fate of porcine and human insulin at the subcutaneous injection site. I. Degradation and absorption of insulins in the rat.

The plasma insulin and serum glucose levels were compared after the subcutaneous and intravenous administration of porcine and human insulin in rats. While no difference was observed in plasma insulin or serum glucose levels with either insulin after intravenous administration, the plasma insulin levels and hypoglycemic effects of human insulin were greater than those of porcine insulin after subcutaneous administration. At various time intervals, radioactivity in subcutaneous tissue was assayed for insulin and/or its metabolites by gel filtration. Using these data, the absorption and degradation rate constants of these substances were estimated according to a one-compartment model. The degradation rate constants of human insulin was approximately half of that for porcine insulin.

Anesthesia↗
PubMed1987

A comparison of the pharmacokinetics of human protamine sodium insulin with human isophane insulin following subcutaneous injection in normal subjects.

The pharmacokinetics of human protamine sodium insulin 0.6 mg% were compared with those of human isophane zinc insulin using the glucose clamp technique. The insulin preparations were administered subcutaneously at a dose of 0.5 U/kg in 7 normal subjects; a placebo injection served as control. Plasma insulin and C-peptide concentrations were then measured over 24 hours. After correction of the results to allow for endogenous insulin secretion the two insulin preparations gave similar values throughout the study except that protamine sodium insulin achieved an earlier peak in plasma insulin concentration (90 minutes) compared to isophane (120 minutes). When measured by an index of the dextrose infusion rate required to maintain euglycaemia the two insulin preparations gave similar values for the first 16 hours, maximum values being obtained during the fourth hour after administration. Using this index isophane zinc insulin gave higher values during the 17th, 19th and 21st hours following administration suggesting it may have a slightly more prolonged action than protamine sodium insulin.

Adult↗
PubMed1998

Ultrastructural analysis of human skin biopsy specimens from patients receiving recombinant human stem cell factor: subcutaneous injection of rhSCF induces dermal mast cell degranulation and granulocyte recruitment at the injection site.

We performed an ultrastructural analysis of 10 skin biopsy specimens that had been obtained from three women who were undergoing daily subcutaneous dosing with recombinant methionyl-human stem cell factor (rhSCF) as part of a phase I clinical trial. The biopsy specimens were obtained at sites of subcutaneous administration of rhSCF, within approximately 1 to 2 hours of rhSCF injection, and, at the same time, at contralateral control sites that had not been directly injected with rhSCF. We previously reported that subcutaneous dosing with rhSCF in these subjects induced the local development of a wheal and flare response, which was associated with evidence of mast cell degranulation, as well as a systemic increase in numbers of cutaneous mast cells. The present electron microscopic analysis revealed that all biopsies of swollen, erythematous rhSCF-injected sites exhibited anaphylactic degranulation of both mature and immature mast cells, an acute inflammatory response characterized by the migration of neutrophils, basophils (some of which exhibited evidence of piecemeal degranulation), and eosinophils through blood vessel walls into the perivascular and extravascular spaces, and edema and fibrin deposition within the interstitium. By contrast, the control biopsies contained no evidence of mast cell degranulation or acute inflammation. However, both control and rhSCF-injected sites exhibited mast cells that were undergoing granule building and maturation. Thus at the doses tested in these subjects, subcutaneous injection of rhSCF induced anaphylactic-type degranulation of dermal mast cells at the injection site, with an acute inflammatory response that was associated with the recruitment of granulocytes. By contrast, mast cells at sites distant from those directly injected with rhSCF exhibited no evidence of enhanced secretion.

Anaphylaxis↗
PubMedDate not supplied

Changes in factor VIII: coagulant activity and von Willebrand factor antigen concentration after subcutaneous injection of desmopressin in dogs with mild hemophilia A.

Four German Shepherd dogs with mild hemophilia A were given Desmopressin (Minirin intranasal solution, Ferring, Malmo, Sweden) subcutaneously at a range of doses in a controlled blind study. No substantial change in plasma FVIII activity was observed 0.5, 1, 2, 4, or 6 hours after administration of Desmopressin. Plasma von Willebrand factor antigen concentrations increased rapidly after doses of 0.4, 1.0, 2.0, and 5.0 micrograms/kg to mean values of 140%, 127%, 120%, and 140% of baseline, respectively. The duration of this increase was dependent on the dose of Desmopressin injected.

Animals↗
PubMed1981

The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system.

We have attempted to verify the suggestion that synovial membrane is the result of mechanical disruption of connective tissue, and may occur at any site. Mechanical disruption of the subcutaneous connective tissue was achieved in rats and mice by the repeated injection of air. The resulting cavities developed a lining structure with many of the features of synovial membrane as judged by electron microscopy, and light microscopy using haematoxylin and eosin and van Gieson stains, esterase activity and immunofluorescent staining for Ia antigen. A structure closely resembling synovium is formed as early as 6 days, providing a convenient method for studying large quantities of facsimile synovial tissue under a wide variety of easily administered stimuli.

Air↗
PubMed1997

Human prostate tumor angiogenesis in nude mice: metalloprotease and plasminogen activator activities during tumor growth and neovascularization of subcutaneously injected matrigel impregnated with human prostate tumor cells.

BACKGROUND: A critical aspect for growth of solid tumors is the development of a blood supply. Our objective was to establish a model for the study of angiogenesis of human prostate tumors by examining the growth of microvessels into Matrigel containing human prostate tumor cells implanted subcutaneously in nude mice. METHODS: Human prostate tumor cell lines PC-3 and LNCaP were injected in Matrigel under the abdominal skin of nude mice and were harvested at 4, 8, and 14 days post-injection. The growth of tumor cells and blood vessels was examined histologically and by immunohistochemical localization of von Willibrand Factor VIII (vWF). Since plasminogen activators and matrix metalloproteases are associated with angiogenesis, the activities and molecular forms of these proteases were determined in Matrigel control and Matrigel-tumor cell subcutaneous implants. RESULTS: Blood vessel formation in the Matrigel implants containing LNCaP and PC-3 cells was demonstrable at 8 days post-injection. However, the pattern of blood vessel formation by the two tumor cell lines was different; PC-3 tumors showed a more invasive phenotype and smaller diameter blood vessels, whereas LNCaP tumors grew as large cellular spheroids surrounded by large, dilated blood vessels. Many blood vessels of PC-3 tumors expressed vWF by day 14 of growth, whereas most blood vessels in LNCaP tumors were immunohistochemically negative for this antigen. Mouse skin blood vessels in the same PC-3 and LNCaP tumor histological sections were positive for vWF. Matrigel contained both plasminogen activator and metalloprotease activities. The plasminogen activator activity in Matrigel control implants was totally inhibited by 4 days post-injection, indicating the presence of an inhibitor provided by the host mouse. LNCaP tumor cells injected did not have appreciable plasminogen activator activity, nor did LNCaP tumors develop plasminogen activator activity with tumor growth post-injection. PC-3 cells did have plasminogen activator activities, which were partially negated after subcutaneous injection (4 days), but then increased again by 8 days post-injection. This increase in plasminogen activator activity was due to urokinase (about 54 kDa) produced by the tumor and not by the mouse host (mouse urine urokinase about 44 kDa). Matrigel alone demonstrated gelatinase B (about 95 kDa) activity in zymograms, and gained considerable gelatinase A (about 70 and 74 kDa) activity after subcutaneous implantation. No metalloprotease activity from the tumor cells could be distinguished over that contributed by the mouse host cells in the Matrigel. Matrigel also contains caseinolytic activities of approximately 56, 80, 85, and 89 kDa. After subcutaneous injection of Matrigel, the 89 kDa form increases considerably in activity and the others are diminished. This pattern is also observed in LNCaP and PC-3 tumors post-injection, except the PC-3 tumors demonstrate increased 56 kDa activity. CONCLUSION: The subcutaneous growth of LNCaP and PC-3 prostate tumor cells in Matrigel in nude mice can be used to study tumor-induced angiogenesis. However, the organization of LNCaP and PC-3 tumor growth and the pattern of microvessels associated with each tumor are different in this system, implying that each tumor has unique influences on the pattern of microvessel development. The mode of action by which this is brought about is not known, but may be due to specific factors produced/ released by the tumor cells.

Animals↗
PubMed1995

Kinetics of plasma cyclic GMP and atrial natriuretic peptide after intravenous, intramuscular and subcutaneous injection of 50 micrograms hANP in man.

Plasma kinetics of immunoreactive natriuretic peptide (IR-ANP) and cyclic guanosine monophosphate (cGMP) were studied after intravenous (i.v.), intramuscular (i.m.) and subcutaneous (s.c.) application of 50 micrograms human ANP (hANP) in six healthy, male volunteers. The study was single blind. Mean base-line IR-ANP value (N = 54) was 10.8 +/- 1.8 pmol/l. Five min after injection peak IR-ANP concentrations were reached i.v.: 149.5 +/- 94, i.m.: 25.6 +/- 10.8 and s.c.: 18.3 +/- 3.3 pmol/l while cGMP levels reached maximum values at 15 min or 30 min after application: i.v.: 30.6 +/- 12.1, i.m.: 19.2 +/- 8.5 and s.c.: 17.3 +/- 12.3 nmol/l with a mean base-line value of 13.2 +/- 2.1 nmol/l. The calculated corresponding areas under the IR-ANP curves (AUC) achieved about 22% bioavailability for i.m. and s.c. in comparison with the i.v. application. cGMP bioavailability was about 32%. No statistical difference was calculated between i.m. and s.c. application of 50 micrograms hANP. Changes in IR-ANP levels after i.m. and s.c. administration were not accompanied with effects on urine and electrolyte excretion while there was only a tendency in urine volume and sodium increase after i.v. administration. In conclusion after i.m. or s.c. application of hANP only a minor fraction (approximately 1/5) of IR-ANP is available in circulation in comparison with i.v. application with little or no biological effects.

Adult↗
PubMedDate not supplied

Combined continuous subcutaneous insulin infusion and multiple subcutaneous injections in type I diabetic patients.

Seven insulin-dependent diabetic patients (aged 16-34 yr) were treated for 10 mo with a combination of continuous subcutaneous insulin infusion (CSII) during the night and premeal boluses of insulin during the day. The technology and strategy of the system are discussed. Three of these patients had been on CSII for 1 yr before the start of this study. Mean fasting (126 +/- 44 mg/dl), mean preprandial blood glucose (131 +/- 54 mg/dl), and mean postprandial blood glucose (216 +/- 73 mg/dl) before starting this treatment fell to 86 +/- 12 mg/dl, 83 +/- 19 mg/dl, and 132 +/- 17 mg/dl, respectively, after 1 mo of treatment. Glycosylated hemoglobin (10.8 +/- 2.9% before the study) reached normal values (7.8 +/- 0.6%) after 2 mo of treatment. Improvement of glycemic control may be achieved with this form of insulin administration, which is of immediate practical application, until an ideal system of insulin delivery becomes available. This technique provides the conditions for testing the hypothesis that near normalization of glycemic control prevents or minimizes the degenerative complications associated with diabetes mellitus.

Adolescent↗