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At least 163 records · Page 9Linked to original sources
PubMed1977

Reaction of foetal tissues to intra-uterine subcutaneous injection of barium sulphate.

Subpannicular injection of sterile barium sulphate in newborn rabbits produces an acute inflammatory response which is clearly seen at 24 hr and is well established at 48 hr. The processes of repair has begun by the 4th day with the appearance of proliferating capillaries and fibroblasts. In rabbit foetuses both vascular and cellular components of the acute inflammatory response are more prominent and appear earlier than in newborn rabbits, being well developed within 24 hr. The process of repair also begins earlier, proliferation of capillaries and fibroblasts being already prominent by 48 hr. By the 4th day the lesion is compact, less cellular and relatively avascular.

Animals↗
PubMed1993

Mobilization of peripheral blood stem cells by subcutaneous injections of yeast-derived granulocyte macrophage colony stimulating factor: a phase I-II study.

A phase I-II study was conducted in 15 patients to determine the tolerability, efficacy and optimal dose of s.c. yeast-derived granulocyte-macrophage colony stimulating factor (GM-CSF) for mobilization of peripheral blood stem cells (PBSC). PBSC were measured by the colony forming unit granulocyte-macrophage (CFU-GM) and burst forming unit erythroid (BFU-E) in vitro colony assays and CD34 flow cytometric analysis. GM-CSF was administered for 12 days as a single daily s.c. injection at 125 micrograms/M2 (n = 3), 250 micrograms/M2 (n = 3), 375 micrograms/M2 (n = 6) and 500 micrograms/M2 (n = 3). At these doses, sustained serum GM-CSF levels of approximately 100-400 pg/ml were observed for at least six hours. Most (97.2% or 175/180) of the planned GM-CSF doses were administered with no serious adverse effects at any of the dose levels. Three leukapheresis procedures were performed before and then after 8, 10 and 12 doses of s.c. GM-CSF. Compared with basal leukapheresis collections, s.c. GM-CSF mobilized leukapheresis collections yielded greater numbers of total white blood cells ([WBC] 15/15 patients or 100%, p < 0.001) mononuclear cells ([MNC] 8/15 patients or 53%, p = 0.55), CFU-GM (11/15 patients or 73%, p = 0.037), BFU-E (9/15 patients or 60%, p = 0.13) and CD34+ cells (6/15 patients or 40%, p = 0.15). The in vitro CFU-GM were augmented approximately two to tenfold in GM-CSF mobilized collections with no clear dose effects from 125-500/micrograms/M2. However, in vivo engraftment time to absolute neutrophil count (ANC) 500/mm3 correlated strongly with GM-CSF PBSC mobilizing dose (r2 = 0.99). We conclude that s.c. yeast-derived GM-CSF is a simple, effective and tolerable method for mobilization of PBSC.

Adult↗
PubMed1991

The pharmacokinetics and pharmacodynamics of lisuride in healthy volunteers after intravenous, intramuscular, and subcutaneous injection.

The plasma concentration of lisuride and prolactin have been measured in twelve healthy male volunteers after IV, IM or SC injection of 25 micrograms lisuride hydrogen maleate as an aqueous solution. After IV administration the plasma lisuride fell in two phases with half-lives of 14 min and 1.5 h. Total clearance was 13 ml.min-1.kg-1. After IM and SC injection the plasma concentrations peaked at 12 to 15 min and the profiles were similar to that found after IV administration. The systemic availabilities were 90% and 94%, respectively. Prolactin concentrations were reduced by a maximum of 60% relative to the normal circadian rhythm after all three routes of administration. The treatments were well tolerated, the only adverse reactions reported by some of the volunteers being mild, transient dizziness, tiredness, and nausea.

Adult↗
PubMed1995

Gastric emptying is accelerated in diabetic BB rats and is slowed by subcutaneous injections of amylin.

Gastric emptying was measured in normal and insulin-treated spontaneously diabetic BB rats using the retention of an acaloric methylcellulose gel containing phenol red delivered by gavage. Dye content in stomachs removed after killing 20 min later was determined spectroscopically, and was compared to that in rats killed immediately after gavage to assess emptying. Diabetic rats had a markedly greater gastric emptying (90.3 +/- 1.7% passed) compared to normal Harlan Sprague Dawley rats (49.1 +/- 4.7% passed; p < 0.001) and non-diabetic BB rats (61.1 +/- 9.2% passed; p < 0.001). The pancreatic beta-cell peptide, amylin, which is deficient in insulin-dependent diabetes mellitus, dose-dependently inhibited gastric emptying in both normal and diabetic rats. The ED50 of the response in normal rats measured by phenol red and novel [3-3H]glucose gavage techniques was approximately 0.4 microgram. This dose was estimated to increase plasma amylin concentration by a mean of approximately 20 pmol/l to concentrations within the range observed in vivo. It is proposed that amylin could participate in the physiological control of nutrient entry into the duodenum and that the accelerated gastric emptying seen in BB rats could be related to their lack of amylin secretion.

Amyloid↗
PubMed1994

Pharmacokinetics, pharmacodynamics and glucose counterregulation following subcutaneous injection of the monomeric insulin analogue [Lys(B28),Pro(B29)] in IDDM.

The aim of these studies was to compare the pharmacokinetics, pharmacodynamics, counterregulatory hormone and symptom responses, as well as cognitive function during hypoglycaemia induced by s.c. injection of 0.15 IU/kg of regular human insulin (HI) and the monomeric insulin analogue [Lys(B28),Pro (B29)] (MI) in insulin-dependent-diabetic (IDDM) subjects. In these studies glucose was infused whenever needed to prevent decreases in plasma glucose below 3 mmol/l. After MI, plasma insulin increased earlier to a peak (60 vs 90 min) which was greater than after HI (294 +/- 24 vs 255 +/- 24 pmol/l), and plasma glucose decreased earlier to a 3 mmol/l plateau (60 vs 120 min) (p < 0.05). The amount of glucose infused to prevent plasma glucose falling below 3 mmol/l was approximately three times greater after MI than HI (293 +/- 26 vs 90 +/- 25 mumol.kg-1 x 60-375 min-1, p < 0.05). After MI, hepatic glucose production was more suppressed (0.7 +/- 1 vs 5.9 +/- 0.54 mumol.kg-1.min-1) and glucose utilization was less suppressed than after HI (11.6 +/- 0.65 vs 9.1 +/- 0.11 mumol.kg-1.min-1) (p < 0.05). Similarly, plasma NEFA, glycerol, and beta-OH-butyrate were more suppressed after MI than HI (p < 0.05), whereas plasma lactate increased only after MI, but not after HI. Responses of counterregulatory hormones, symptoms and deterioration in cognitive function during plasma glucose plateau of 3 mmol/l were superimposable after MI and HI (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

Within-patient variation of the pharmacokinetics of subcutaneously injected biphasic insulin aspart as assessed by compartmental modelling.

AIMS/HYPOTHESIS: Pharmacokinetics of s.c. administered insulin preparations have been widely studied, mostly using descriptive measures such as AUC, time to peak, or the peak plasma concentration. Several compartmental modelling studies of single-bolus s.c. insulin pharmacokinetics have also appeared, with contrasting results regarding the feasibility of insulin pharmacokinetics modelling and the appropriate level of detail for such models. In this paper, we used compartmental models to study the pharmacokinetics of biphasic insulin aspart administered by multiple s.c. injections. The main objective was to assess the magnitude of the inter-and intra-subject variation in the kinetics. MATERIALS AND METHODS: Analyses were performed on 24-h serum insulin concentrations measured in 20 type 1 diabetes subjects given three daily s.c. injections of biphasic insulin aspart. RESULTS: Preliminary analysis of the AUC:dose ratio showed that the apparent kinetics are not constant throughout the three daily injections of the compound. A simple and robust compartmental model was shown to be appropriate for interpreting the observations, provided that one of its parameters (the first-order rate constant for transfer from the s.c. depot to plasma) is allowed to vary between injections. CONCLUSIONS/INTERPRETATION: Population estimates of the chosen model show that intra-subject variations between injections is of the same order of magnitude as inter-subject variation, partially explaining the difficulties encountered when individually tailoring intensified insulin therapy. We conclude that the explicit consideration of a rather simple kinetic model will allow better experimental designs in the future study of s.c. insulin preparations.

Area Under Curve↗
PubMed2000

Reinforcing effects of contingently administered subcutaneous injections of etonitazene in rats.

RATIONALE: Response-contingent injections of opioids have been shown to control behavior in various species. OBJECTIVE: To determine whether s.c. injections of etonitazene (ETZ) could maintain behavior in rats when administered under a single fixed-interval schedule. METHODS: Rats were trained to lever press for eight 45-mg food pellets under a single fixed-interval (FI) 10-min schedule of reinforcement: following passage of the 10-min interval, each lever press resulted in a pellet delivery until eight pellets were obtained. Delivery of the reinforcer was signaled by a change in visual stimulus conditions. Once stable responding for the food pellets under the FI 10-min schedule was established, a s.c. injection of 3.2 micrograms/kg ETZ was administered to the rat by the investigator following schedule completion and delivery of the food pellets. After receiving the drug injection, rats were returned to the experimental chamber for 30 min and exposed to the same stimulus conditions that accompanied food reinforcement. Across sessions, the number of food pellets was decreased until rats were responding solely for the drug. RESULTS: Responding for the s.c. administered drug stabilized and persisted across sessions. When saline vehicle injections were substituted for the drug injections, responses diminished across sessions to levels below that of the drug baseline. Subsequent alternating blocks of ETZ and vehicle injections produced respective increases and decreases in responding. CONCLUSION: This study demonstrates that response-contingent s.c. injections of a drug can control behavior in rats, systematically replicating a previous experiment that used the i.p. route. Since all pertinent operant behavior is emitted prior to the administration of drug, this procedure can be used for testing the reinforcing effects of a drug without interference from any direct (rate-altering) drug effects. The present findings also extend the conditions under which drugs of abuse may reinforce behavior.

Animals↗