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At least 19 recordsLinked to original sources
PubMed1985

Fate of porcine and human insulin at the subcutaneous injection site. II. In vitro degradation of insulins in the subcutaneous tissue of the rat.

We compared the in vitro degradation of porcine and human insulin in the subcutaneous tissue of rat. The insulin degrading activity was largely confined to the 160000 X g supernatant fraction of subcutaneous tissue. The degradation of human insulin was approximately half that of porcine insulin in the supernatant fraction. The degradation of porcine insulin in subcutaneous tissue was inhibited by bacitracin, leupeptin, phosphoramidon, and Z-Gly-Pro-Leu-Gly, though the human insulin degradation was not. The degradation of both insulins was accelerated by glutathione. While the proteolytic enzyme activities of cathepsin-B and collagenase-like peptidase were detectable in subcutaneous tissue, chymotrypsin, elastase, kallikrein, alpha-thrombin, and trypsin activities were almost negligible. These in vitro studies suggest that human insulin is comparatively stable against proteolytic enzymes, probably collagenase-like peptidase or cathepsin-B, in the subcutaneous tissue, which support the in vivo evidence.

Animals↗
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↗
PubMed1990

Increased subcutaneous adipose tissue blood flow in UVB-inflamed human skin. The existence of a cutaneous-subcutaneous reflex mechanism?

In 4 healthy subjects a skin area 10 mm in diameter was exposed to twice the minimal erythema dose of UVB. Subcutaneous blood flow (SBF) in the area was measured by the local 133-Xenon washout technique before and 8, 24, 48 and 72 h after induction of inflammation. Local skin temperature (TS) was monitored with electrical thermocouples. SBF gradually increased by 400% and peaked 24 to 48 h after induction of inflammation, while TS peaked after 8 h (+3 degrees C). The disparity in skin temperature and subcutaneous blood flow indicates that TS is not the governing factor in the increase in SBF. As release of inflammatory mediators from the cutis influencing the subcutis and a local effect of UVB on subcutis are unlikely, we suggest the existence of a cutaneous-subcutaneous vascular reflex mechanism as an explanation for the increased subcutaneous blood flow.

Adipose Tissue↗
PubMed1992

Treatment of migraine attacks with subcutaneous sumatriptan: first placebo-controlled study. The Subcutaneous Sumatriptan International Study Group.

The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like (5HT1-like) receptor agonist sumatriptan are presented. We studied the efficacy and tolerability of subcutaneous injections of 1 mg, 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind, placebo-controlled, parallel-group, multicentre clinical trial. Six-hundred and ninety patients were randomized and 685 received study medication. At 30 min, reduction of headache severity to mild or none (primary efficacy endpoint) was achieved in 22% (95% CI: 15-28%) of placebo-treated patients and in 39% (CI: 31-46%) of patients treated with 1 mg sumatriptan, 44% (CI: 36-51%) treated with 2 mg sumatriptan and 55% (CI: 48-63%) treated with 3 mg sumatriptan. Differences from placebo were 17% (CI: 8-27%) for 1 mg sumatriptan, 22% (CI: 13-32%) for 2 mg sumatriptan and 34% (CI: 24-44%) for 3 mg sumatriptan (p < 0.001 for all three comparisons). Other migraine symptoms were also more effectively treated by sumatriptan than by placebo. Subsequently, an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders. Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80%. Adverse events after sumatriptan were minor and short-lived. We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks.

Adolescent↗
PubMed1992

Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial.

In a prospective multicenter trial, 149 consecutive patients with phlebographically proven proximal and/or distal deep vein thrombosis of the leg were randomly allocated to receive subcutaneously for 10 days either low molecular weight heparin CY 216 (Fraxiparine) in a fixed dose or unfractionated heparin (UFH) in doses adjusted according to the activated partial thromboplastin time. Pre- and post-treatment phlebograms were assessed blindly using the Arnesen's score system in 134 patients available for analysis of the treatment efficacy. The mean phlebographic score after 10 days of treatment was significantly decreased in both groups (p less than 0.001) in comparison with the baseline score but the difference in score changes between the two groups was not statistically significant. There was an improvement in 45/68 patients (66%) in the Fraxiparine group and in 32/66 patients (48%) in the UFH group, and an increase in the thrombus size in 10/68 (15%) and 12/66 (18%), respectively. One symptomatic non-fatal pulmonary embolism and one major bleeding episode were observed in the UFH group. During a follow-up period of 3 months, two rethromboses had occurred in the UFH group and none in the Fraxiparine group. It is concluded that subcutaneous fixed dose Fraxiparine is safe and at least as effective as subcutaneous adjusted UFH in the treatment of deep vein thrombosis.

Adult↗
PubMed1988

[Clinical experience with single and multiple subcutaneous administration of LHRH analog Buserelin (Hoe 766) in prostatic carcinoma: endocrinological study of optimum subcutaneous doses].

Seventy three patients with prostatic carcinoma (PC) and 7 patients with benign prostatic hypertrophy (BPH) in 12 institutes subcutaneously received single and multiple doses of Hoe 766, and clinical efficacy, safety and endocrine effects of drug were examined. In a single doses study, six doses were subcutaneously administered to 7 BPH and 3 with PC. Gonadotropin and testosterone levels in the blood were increased following all these doses. In a multiple study, 7 kinds of doses were given to 40 patients with PC. The optimum doses of subcutaneous injection was decided to be 500 x 3 micrograms/day based on gonadotropin and testosterone suppression. Objective response by NPCP's criteria was observed in 35.3% (complete response 5.9%, partial response 29.4%) following 3 months of Hoe 766 treatment. Adverse reactions were observed in 9 cases (12.8%): Treatment was discontinued in 3 cases (eruption in 2, nausea and vomiting in 1), and continued in 6 cases (8.6%) without any treatment required. Buserelin was thus considered to be an effective, safe drug to treat prostatic carcinoma.

Aged↗
PubMed1976

Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue.

1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.

Adipose Tissue↗
PubMedDate not supplied

Variation of insulin absorption during subcutaneous and peritoneal infusion in insulin-dependent diabetic patients with unsatisfactory long-term glycaemic response to continuous subcutaneous insulin infusion.

The aim of present study was to analyse the reproducibility of plasma-free insulin profiles of subcutaneously (CSII) and intraperitoneally (CIPII) administered insulin in 6 C-peptide-negative, type 1, diabetic patients. The patients were selected for CIPII because of unsatisfactory, long-term, metabolic response to CSII. Plasma-free insulin was measured repeatedly, twice during subcutaneous infusion and twice during intraperitoneal infusion, for 4 hours, following a standard breakfast. In the CSII experiment, insulin was given as a meal-dose of 0.1 U per kg body weight, and in the CIPII experiment the meal-dose was 0.05 U per kg body weight. The dose-induced peak occurred earlier after the CIPII than with the CSII (60.0 +/- 8.0 vs 133.6 +/- 16.3 min). In conclusion, the intra-patient coefficient of variation (C.V.) of plasma-free-insulin profiles at 0-60 min and 0.240 min, as well as the peak time, were markedly lower for CIPII insulin than for CSII, indicating a more reproducible way of insulin administration with CIPII in this selected group of patients.

Absorption↗
PubMed1988

Patient-controlled subcutaneous hydromorphone versus continuous subcutaneous infusion for the treatment of cancer pain.

Twenty-five patients with pain due to advanced cancer were randomized to receive patient-controlled sc injections (PCIs) of hydromorphone (HM) versus continuous sc infusion (CSCI) of HM by means of a Pharmacia 5200 pump. Each self-injection of HM during PCI was equivalent to 4 hours of CSCI. After 3 days, a crossover occurred, and patients received the alternate treatment for 3 days. During both phases of the study, patients could request extra doses of HM from their nurses. In 22 patients able to be evaluated, pain intensity (visual analogue, 0-100 mm) at 9:00 a.m. and 4:00 p.m. was 31 +/- 23 and 28 +/- 18 mm, respectively, on PCI versus 28 +/- 18 and 27 +/- 17 mm, respectively, on CSCI [P = not significant (NS)]. The total dose of HM was 168 +/- 197 and 181 +/- 234 mg on PCI and CSCI, respectively (P = NS). No significant difference was found in nausea, drowsiness, or number of hours of sleep. The total number of extra doses of HM was 6 +/- 7 on CSCI versus 2 +/- 3 on PCI (P = .007). At the end of the study, patients chose PCI and CSCI in seven and 10 cases, respectively (P = NS; 5 patients expressed no preference). We conclude that both methods were similar in regard to effectiveness and toxic effects in short-term hospital use.

Female↗
PubMed1989

[Urinary bioavailability of sodium-2-mercaptoethanesulfonate (Uromitexan) following intravenous, subcutaneous and continuous subcutaneous administration].

The dose-limiting urotoxicity of the oxazaphosphorines (t1/2 = 4-15 h) is due to renal elimination of metabolites such as acrolein. The occurrence of hemorrhagic cystitis can be safely prevented by the concomitant use of i.v. or oral 2-mercaptoethanesulfonate sodium (DCI MESNA; Uromitexane). The bioavailability of oral MESNA is in the range of 20-50% and its unpleasant taste severely limits patient compliance. Due to the short half-life of MESNA (approx. 40 min) a regular fractionated or continuous administration is mandatory. In 6 healthy volunteers we have studied the pharmacokinetics of urinary MESNA elimination for the assessment of MESNA bioavailability after i.v. and s.c. drug administration. MESNA was given at doses of 400 mg for i.v. and s.c. bolus injections and 800 mg for continuous s.c. administration by a portable infusion pump. For the s.c. route an isotonic solution was prepared. The total amount of urinary thiols was assessed by the Ellman method (photometric reading at 412 nm). Total elimination of i.v. MESNA was 83.2 +/- 3.4% of the dose administered. The respective results for s.c. bolus and s.c. continuous drug administration were 81.9 +/- 3.4% and 79.4 +/- 3.6% of the dose. Continuous administration theoretically will provide optimal uroprotection from short term (hemorrhagic cystitis) and long term (bladder fibrosis and cancer) toxicity.

Biological Availability↗
PubMed1976

Growth suppression of subcutaneously inoculated hepatic tumors after injection of syngeneic liver cells into the subcutaneous tissue of rats.

One week after the sc injection of minced tissues of the livers, kidneys, or spleens of W, Donryu, and MP rats into the left back of syngeneic rats, ascites-type tumor cells derived from rat hepatoma (AH 130) or Walker carcinosarcoma cells derived from rat breast tumor were inoculated sc into the right back. Ascites hepatoma cell growth was slowest in the group given the liver preparation, whereas no significant difference was noted in the growth of Walker carcinosarcoma in all groups. The results were similar in all strains.

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↗
PubMed1975

[The subcutaneous vascular system (lower extremity): studies on micro-preparations].

At the level of fascial penetration the cutaneous arteries of the lower extremity are constantly accompanied by 1 or 2 communicating veins of varying diameter. Usually, they penetrate the fascia in rows via the muscular interstitium. There they give up branches to the fascial vascular network, to pre- and subfascial areolar tissue and possibly to the muscle origins on the fascia, or to the intermuscular septa. The texture of the fascia itself determines the structure of fascial openings for the cutaneous vessels. In the subcutaneous tissue the arteries are accompanied by 1 or 2 veins (Vv. comitantes). Numerous arterio-arterial and intervenous anastomoses form a subcutaneous network of vascular bundles. Two anastomosing venous systems can be distinguished in the subcutis: The small Vv. comitantes are fed primarily by the subcutaneous adipose lobes, and end in communicating veins or flow into the subcutaneous veins (epifascial veins). These large subcutaneous veins on the other hand are responsible for the actual outflow from the venous network of the cutis. They form the saphenous system or empty into larger communicating veins. Between the subcutaneous arterioles and accompanying venules there are numerous capillary webs. In addition direct capillaries and looped as well as meandering or knotted arterio-venous shunts are found. The subcutaneous vascular bundles are fixed by a connective tissue. There are often typical capillary meshes within arterial sheat, oriented like a rope-ladder. They undergo prenatal development. The subcutaneous (epifascial) veins are surrounded by areolar tissue on the cutaneous as well as on the fascial side. Fibers from the accompanying connective tissue criss-cross into the adventitia and thereby anchor the veins in a movable fashion. Typical vascular patches with plane capillary networks characterize the areolar tissue around the subcutaneous veins, which is differentiating at the 2nd half of the fetal period. Within are also capillary loops and convoluted arterio-venous shunts.

Adult↗
PubMed1991

Intravenous insulin infusion to simulate subcutaneous absorption. Bioavailability and metabolic sequelae.

OBJECTIVE: To determine the bioavailability and bioactivity of subcutaneously injected insulin. RESEARCH DESIGN AND METHODS: A randomized block design with six male mongrel dogs as subjects. In protocol 1, purified pork insulin was infused intravenously to simulate the pattern of appearance in the blood that would have been expected from subcutaneous injection. Three intravenous doses (0.05, 0.10, and 0.15 U/kg) were infused on separate days in a pattern (0-300 min) designed to approximately simulate the absorption rate of subcutaneously injected insulin. In protocol 2, interscapular subcutaneous injections of pork insulin at 0.10 U/kg were made. RESULTS: Integrated insulin, decrement in plasma glucose, and maximal glucose clearance for subcutaneous injection experiments were similar to intravenous infusion of equal dose (P greater than 0.10) but significantly different from low-dose infusions (P less than 0.025). Similar results were observed for hepatic glucose output and glucose uptake. Hypoglycemia elicited counterregulatory responses that appeared to be under a threshold differentiated at a plasma glucose of approximately 3 mM. Integrated insulin was plotted against insulin dose to create dose-response curves for intravenous data. The curve was then used to predict the actual appearance rate of insulin in plasma for subcutaneous injection. The estimated bioavailability of subcutaneous insulin was 103.0 +/- 10.5% of the injected dose. CONCLUSIONS: We concluded that, in dogs, insulin delivered subcutaneously in the interscapular area is not significantly degraded before absorption, resulting in metabolic effects equal to intravenous insulin infusion of equivalent dose.

Animals↗
PubMed1991

Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans.

The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure (BPa) decreased by 23%-30% and heart rate (fc) increased but only during NTG infusion (+22%; P less than 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: -26%, P less than 0.01; SNP: -34%, P less than 0.02] and subcutaneous vascular resistance changed only with SNP (-31%, P less than 0.02). After hypotension was discontinued the subcutaneous blood flow decreased (-13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between fc and BPa (NTG: r = -0.525, P less than 0.01; SNP: r = -0.622, P less than 0.01) as well as with subcutaneous blood flow (NTG: r = -0.653, P less than 0.001; SNP: r = -0.573, P less than 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W.m-1.degree C-1 vs SNP 0.42 (SEM 0.1) W.m-1.degrees C-1, P less than 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P less than 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects.

Adult↗
PubMed1979

Evidence that protease inhibitors reduce the degradation of parathyroid hormone and calcitonin injected subcutaneously.

1 Agents known to delay absorption from a subcutaneous site were tested in chicks for their ability to prolong the hypercalcaemic response to parathyroid hormone (PTH). 2 Polyvinylpyrrolidone was found to enhance the response but gelatine greatly reduced the 2 h hypercalcaemia. 3 The reduction by gelatine was reversed when the protease inhibitor aprotinin was added to the injection vehicle, and hypercalcaemia then persisted for more than 8 h. 4 Of other protease inhibitors studied, epsilon-aminocaproic acid was also found to enhance the hypercalcaemic response to subcutaneous PTH and its fragments but, unlike aprotinin, it was ineffective in the presence of gelatine. 5 By radioimmunoassay and bioassay respectively, it was confirmed that aprotinin raised circulating levels of PTH and also of another peptide hormone, calcitonin, injected subcutaneously. 6 Addition of calcium to the solutions injected subcutaneously abolished the hypercalcaemic response to PTH while injection of calcium and PTH simultaneously but at separate sites left the response unaltered. 7 The two protease inhibitors, epsilon-aminocaproic acid and aprotinin, each restored the response to subcutaneous PTH despite the presence of calcium at the injection site. 8 It was concluded that protease inhibitors injected subcutaneously with PTH and calcitonin in the chick reduced the rate of degradation of these hormones and that the proteases responsible for hormone degradation at the subcutaneous injection site may be released or activated by calcium ions.

Animals↗