[A case of transplantable sarcoma of rat growing in the injected area of the skin by the repeated subcutaneous injection of 0.5% formaldehyde water solution].
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Animals↗
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Results for “Injections, Subcutaneous”
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Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety.
Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses of 0, 5, 30, or 75 microg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects of once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH( 1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75-microg/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.
Animals↗
Clinical evaluation of pain during subcutaneous injections of low molecular weight heparins in healthy volunteers.
In order to compare the intensity and the duration of the pain following the subcutaneous injection of low molecular weight heparins, 0.4 ml nadroparin, 0.4 ml enoxaparin and 0.4 ml placebo (NaCl 0.9%) were administered at 1 week intervals to 12 healthy volunteers in a randomised, double-blind, three-period study. Pain was assessed by visual analogue and verbal category scales. Based on visual analogue scale scores, nadroparin resulted in significantly less pain than enoxaprin at 1 and 5 min after injection (6.2 +/- 2.6 mm vs 21.9 +/- 5.9 mm; P < 0.05 and 3.5 + 1.5 mm vs 14.3 +/- 4 mm; P < 0.05, respectively, mean +/- s.e. mean). Similar results were obtained using verbal category scale. Confidence interval testing for difference between groups showed that nadroparin injection resulted in less pain than enoxaparin at 1 min (-15.8: -31.2 to -0.4 mm).
Adult↗
Long-term histological response to subcutaneously injected Polytef and Bioplastique in a rat model.
OBJECTIVE: To compare the long-term carcinogenic effect of Polytef and Bioplastique in the subcutaneous space of the rat. MATERIALS AND METHODS: One hundred Sprague Dawley rats received a subcutaneous injection of one of two particulate plastics; subsequently 48 of those injected with Polytef paste containing polytetrafluoroethylene, 48 injected with silicone containing Bioplastique, and 48 control animals were available for assessment. Animals were killed when they became unwell, developed a tumour, or were 2 years of age. The injection site and all major organs and tumours were examined histologically. RESULTS: One or more tumours were found in 30 Polytef-injected rats, 34 Bioplastique-injected animals and 36 of the controls. The majority of the tumours were breast and pituitary adenomas with a similar incidence in each group. No tumours were found at the injection site of the Polytef-injected animals. Four poorly differentiated sarcomas were found on the back of Bioplastique-injected rats; three were intimately associated with silicone particles, whereas the fourth was separate from the injection site. CONCLUSION: This study would suggest that the carcinogenic risk from injectable plastics is low, but further work should be conducted with the larger particles, to ensure that their use in humans is safe.
Animals↗
Rapid induction of mammary cancer by repeated subcutaneous injection of the trans-3,4-dihydrodiol of 7,12-dimethylbenz[a]anthracene in the female Sprague-Dawley rat.
The oral administration of a single 20mg dose of 7,12-dimethylbenz[a]anthracene regularly and rapidly induces mammary cancer in 50 day-old Sprague-Dawley female rats [Experimental Leukemia and Mammary Cancer, 1979, p. 74]. Several mechanisms by which 7,12-dimethylbenz[a]anthracene induces mammary cancer have been proposed and various derivatives have been implicated as possible proximate or ultimate electrophilic and carcinogenic forms of this hydrocarbon. Here we show that 7,12-dimethylbenz[a]anthracene-trans-3,4-dihydrodiol rapidly induces mammary cancer by repeated subcutaneous injection in a high proportion of female Sprague-Dawley rats without malignancies at the site of injection, whereas its more lipid soluble diacetate derivative induced injection site sarcomas in addition to distal mammary cancers. By contrast, repeated subcutaneous injection of 7,12-dimethylbenz[a]anthracene and its 7-meso-aldehyde derivative induced subcutaneous sarcoma in most, if not all, rats and a few mammary cancers.
9,10-Dimethyl-1,2-benzanthracene↗
Changes in bleeding patterns with depot medroxyprogesterone acetate subcutaneous injection 104 mg.
OBJECTIVE: This study aims to assess changes in bleeding patterns with the use of depot medroxyprogesterone acetate (DMPA) 104 mg/0.65 ml subcutaneous injection (DMPA-SC 104). STUDY DESIGN: An analysis was conducted using data from two 1-year, noncomparative clinical trials (N=1787) and a 2-year randomized study comparing DMPA-SC 104 (N=266) with DMPA intramuscular injection (DMPA-IM). Bleeding was analyzed per 30-day interval by category and number of days. Analyses also were performed for age and body mass index (BMI) subgroups and for the percentages of women shifting from bleeding/spotting to amenorrhea after each injection. RESULTS: Each study showed decreased incidence of irregular bleeding and increased amenorrhea with continued use of DMPA-SC 104. Rates of amenorrhea at Month 12 (52-64% across studies) and Month 24 (71% in the 2-year trial) were comparable with those originally reported for DMPA-IM. Changes in bleeding patterns showed no consistent differences according to age or BMI. The percentages of subjects shifting from bleeding and/or spotting to amenorrhea increased with each subsequent injection. CONCLUSION: Clinical data show that the incidence of amenorrhea increases over time with the use of DMPA-SC 104.
Adult↗
Long-term persistence of low-molecular-weight material with anti-factor Xa activity contributes to anticoagulant and antithrombotic effects after subcutaneous injection of CY 216 in the rabbit.
This study was done to document further the mechanism of the antithrombotic effect of CY 216 after subcutaneous injection in the rabbit. We first measured the circulating anti-factor Xa and anti-thrombin activities expressed in either International Unit or Standard Independent Unit and from these activities we calculated the above critical length material (ACLM) and below critical length material (BCLM) levels. The clearance of the BCLM was half that of the ACLM. Then we determined the inhibitory effect of CY 216 on thrombin generation (TG) in platelet-poor plasma (PPP) and in whole blood. TG was both inhibited and delayed in whole blood, while it was only inhibited in PPP. The IC50 on TG in PPP and in whole blood were 1.80 +/- 0.16 and 4.33 +/- 1.01 micrograms.ml-1 respectively. After the injection, the inhibition of TG was significant as long as BCLM was detectable. The duration of the antithrombotic effect was essentially correlated to the ACLM level in the Wessler-thromboplastin model and to the BCLM level in the Wessler-serum model. Taken together, these results demonstrate that both ACLM and BCLM components of CY 216 are involved in its anticoagulant effect ex vivo as well as in its antithrombotic activity in vivo, and that the relative contribution of BCLM increases with the time after administration.
Animals↗
Acute pneumonitis after subcutaneous injections of silicone for augmentation mammaplasty.
In a period of 3 years, seven cases of acute pneumonitis have been found after patients have been subcutaneously injected with silicone for the sole purpose of augmentation mammaplasty. Adverse symptoms following these silicone injections were fever, hypoxemia, hemoptysis, and abnormal diffuse bilateral alveolar infiltrates in both lungs. Pulmonary hemorrhaging occurred, and this was substantiated by using the bronchoscope with the bronchoalveolar lavage (BAL). The alveolar macrophage obtained from the BAL contained large quantities of pleomorphic cytoplasmic particles, which in actual fact were silicone particles. They were identified as silicone by scanning electron microscopy and energy-dispersive analysis of x-rays. This evidently showed that silicone diffusion into the circulatory system and subsequent embolization of the lung. Pulmonary function studies had shown restrictive changes with increase or normal single-breath carbon monoxide diffusing capacity (Dsb). Perfusion lung scans were interpreted as showing diffuse abnormalities consisting of decreased peripheral uptake. Acute hypoxemic respiratory failure was noted in four of these patients. Silicone injections of this nature were therefore a respiratory risk and caused the inducement of pneumonitis.
Acute Disease↗
Time-action profile of inhaled insulin in comparison with subcutaneously injected insulin lispro and regular human insulin.
OBJECTIVE: This study compares the time-action profile of inhaled insulin (INH; Exubera) with that of subcutaneously injected insulin lispro (ILP) or regular human insulin (RHI) in healthy volunteers. RESEARCH DESIGN AND METHODS: In this open-label, randomized, three-way, crossover study, 17 healthy male volunteers were given each of the following treatments in random order: INH (6 mg), ILP (18 units), or RHI (18 units). Glucose infusion rates and serum insulin concentrations were monitored over 10 h. RESULTS: INH had a faster onset of action than both RHI and ILP, as indicated by shorter time to early half-maximal effect (32 vs. 48 and 41 min, respectively; P < 0.001 for IHN vs. RHI and P < 0.05 for IHN vs. ILP). Time to maximal effect was comparable between INH and ILP (143 vs. 137 min; NS) but was shorter for INH than RHI (193 min; P < 0.01). The maximal metabolic effect of INH was comparable with RHI but lower than ILP (8.7 vs. 9.8 vs. 11.2 mg . kg(-1) . min(-1), respectively; P < 0.01 for INH vs. ILP). The duration of action of INH, indicated by time to late half-maximal effect (387 min), was longer than ILP (313 min; P < 0.01) and comparable to RHI (415 min; NS). Total glucodynamic effect after inhalation of INH was comparable to both ILP and RHI (NS). Relative bioefficacy of INH was 10% versus RHI and 11% versus ILP. No drug-related adverse events were observed. CONCLUSIONS: INH had a faster onset of action than RHI or ILP and a duration of action longer than ILP and comparable to RHI. These characteristics suggest that inhaled insulin is suitable for prandial insulin supplementation in patients with diabetes.
Administration, Inhalation↗
Recombinant human endostatin administered as a 28-day continuous intravenous infusion, followed by daily subcutaneous injections: a phase I and pharmacokinetic study in patients with advanced cancer.
BACKGROUND: Endostatin is an endogenous collagen XVIII-fragment with anti-angiogenic properties and remarkable antitumor activity in mice. Preclinical data suggest that continuous low dose administration of endostatin is much more potent than intermittent dosing. The feasibility of this approach is tested in a phase I study. PATIENTS AND METHODS: We determined the safety and pharmacokinetic profile of 4-week continuous intravenous infusion of recombinant human (rh)-endostatin, followed after an interval of 1 week by twice daily subcutaneous injections in patients with advanced cancer. Thirty-two patients received rh-endostatin in six dosing cohorts, ranging from 3.75 mg/m(2)/day to 120 mg/m(2)/day. Serum endostatin pharmacokinetics, toxicity and antitumor response were determined. RESULTS: A total of 160 cycles were delivered without significant toxicities. Pharmacokinetic analysis showed a linear increase of steady-state serum endostatin concentrations with dose (i.v. r(2)=0.96; s.c. r(2)=0.99) reaching 300--1,000 ng/ml for the two highest doses, with considerable interpatient variation. The main pharmacokinetic values for both routes of administration were similar. The apparent steady-state concentration and AUC reached at 60--120 mg/m(2)/day were within the range expected to induce anti-angiogenic and antitumor effects based on preclinical tumor models. Although no objective responses were observed, two patients had long-lasting stable disease (defined as a tumor increase<100%). CONCLUSION: rh-endostatin was safely administered both by continuous infusion and by twice daily subcutaneous injections up to 120 mg/m(2)/day. Predictable pK was seen in this dose range and the target endostatin levels were reached from 60 mg/m(2)/day and above.
Adult↗
Effect of storage temperature of insulin on pharmacokinetics and pharmacodynamics of insulin mixtures injected subcutaneously in subjects with type 1 (insulin-dependent) diabetes mellitus.
These studies were undertaken to assess the influence of storage temperature of insulin vials on pharmacokinetics and pharmacodynamics of a mixture of lente insulin (Monotard HM) and regular insulin (Actrapid HM) injected subcutaneously. Seven subjects with Type 1 (insulin-dependent) diabetes mellitus were studied twice after overnight normalization of plasma glucose. A mixture of lente insulin (0.22 U/kg) and regular insulin (0.11 U/kg) was prepared from insulin vials kept either refrigerated (approximately 4 degrees C) or at room temperature (approximately 18 degrees C) and injected subcutaneously (abdomen). Euglycaemia was maintained for the following 16 h by glucose infusion at variable rate. With refrigerated insulin, the plasma free insulin peak was greater (53 +/- 5 versus 45 +/- 6 mU/l) and occurred earlier (2.5 +/- 0.2 versus 6 +/- 0.3 h), and the glucose infusion rate showed a greater (16.5 +/- 1.2 versus 14.5 +/- 0.9 mumol.kg-1.min-1) and earlier peak (3.2 +/- 0.2 versus 6 +/- 0.4 h) as compared to that occurring with the non-refrigerated insulin (p less than 0.05). However, 6 h after insulin injection, both plasma free insulin and glucose infusion rate were 30% lower with the mixture of refrigerated as compared to that of non-refrigerated insulin (p less than 0.05). In contrast, when NPH-insulin (Protaphane HM) was mixed with regular insulin and injected in 4 out of the 7 diabetic patients, the storage temperature of insulin vials had no effect on the pharmacokinetics and pharmacodynamics of the mixture.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Disposition of antimony and aminosidine combination after multiple subcutaneous injections in dogs.
The disposition of a combination of antimony (Sbv) (12.8 mg/kg) and aminosidine (AM) (10 mg/kg) in 10 healthy Beagle dogs after multiple subcutaneous injections is described. Sbvplasma concentrations were determined by atomic absorption spectrometry, and AM by ion-pair liquid chromatography, using a fluorimetric detector. Sbvreached Cmaxat 60 min, and for about 1 h plasma levels were homogeneously stabilized between 10.78 and 11.76 microgram/mL; by 12 h, Sbvplasma concentrations were close to the detection limit (0.3 microgram/mL). AM Cmaxvalues were recorded after 1 h (30.6+/-3.11 microgram/mL, mean +/- SD), and plasma levels reached values close to the detection limit (0.15 microgram/mL) between 7 and 8 h after injection. Sbvkinetic parameters did not appear modified by the presence of AM. Moreover, repeated injections of the combination did not modify the kinetic behaviour of the two drugs and did not alter the renal function of the animals. The superimposition analysis of the Sbvdata suggests that a twice daily injection of the metal at a dose of 12.8 mg/kg would be sufficient to maintain inhibitory Sbvconcentrations similar to those recorded in humans.
Amebicides↗
Comparison between ropivacaine and bupivacaine after subcutaneous injection in pigs: cutaneous blood flow and surgical bleeding.
In this randomized, blinded study, we sought to determine whether the vasoconstriction produced by ropivacaine after subcutaneous injection is sufficient to decrease surgical bleeding. Anesthesia was induced in seven piglets (weight, 12.2-20.4 kg) with intraperitoneal thiopental and maintained with intravenous methohexital. Five sites were injected with 10 ml of one of the following solutions: 0.25% ropivacaine, 0.25% bupivacaine, either solution plus 5 micrograms/ml epinephrine, or saline. Another site was left uninjected for control. Capillary blood flow was measured at each site with a laser Doppler before and ten minutes after the injections. An incision 5 cm in length was then made through the dermis, and blood loss was measured over ten minutes. We found no significant differences in capillary blood flow and blood loss between bupivacaine and ropivacaine. Addition of epinephrine decreased capillary blood flow (p less than 0.05) and tended to decrease blood loss. Capillary blood flow correlated with blood loss (r2 = 0.106; p less than 0.05). We conclude that, in contrast to previous studies, ropivacaine did not decrease capillary blood flow in our model. Similarly, ropivacaine did not reduce bleeding from surgical incisions. The reason for these surprising results is not clear but is unlikely to be the larger volume of solutions injected because no such effect was observed with saline alone.
Amides↗
Leg ulcers following subcutaneous injection of a liquid silicone preparation.
We present an unusual case of leg ulcers occurring 23 years after the patient had received large-volume subcutaneous injections of a liquid silicone preparation into her legs for cosmetic reasons. Light microscopy of a biopsy specimen from the edge of the ulcer showed optically clear vacuoles in the dermis, together with a mixed cellular infiltrate. Scanning electron microscopic studies revealed amorphous spherules within the vacuoles, and energy-dispersive spectroscopy established the presence of silicon in these spherules. Nearby tissue not containing spherules did not show a silicon peak. This case adds to the growing documentation of morbidity associated with injections of silicone of uncertain purity.
Biopsy↗
Specific immunosuppression by local lymphoid irradiation using subcutaneous injection of palladium-109 labeled allogeneic lymphocytes.
We have previously shown that intravenously administered palladium-109 labeled lymphocytes (Pd-L) migrated specifically to peripheral lymphoid organs where they caused selective lymphoid irradiation resulting in significantly prolonged cardiac allograft survival. This study evaluates the biodistribution of subcutaneously injected allogeneic Pd-L and the capacity of such labeled cells carrying a large dose of irradiation at a local site to attract and subsequently delete alloreactive T lymphocytes. It was hypothesized that subcutaneously administered allogeneic lymphocytes labeled with a large dose of palladium-109 will attract and then kill by irradiation the host effector cells which might permit prolongation of donor-specific allograft via partial clonal deletion. The results showed that 80% (injected dose) of subcutaneously injected allogeneic Pd-L remained at the site of administration while 20% of injected dose/gram was localized in the ipsilateral popliteal lymph node. No significant radioactivity was found in the other lymphoid and nonlymphoid organs. Pd-L effectively deleted the donor-specific effector cells, as measured by specific unresponsiveness to donor lymphocytes in mixed lymphocyte reaction. Donor cardiac allograft survival, however, was not prolonged over that found in naive recipient controls, although it was significantly prolonged when compared to cardiac allograft survival in controls sensitized by identical injections of unmodified subcutaneous allogeneic lymphocytes (mean survival time +/- SD of 6.5 +/- 0.8 vs. 3.0 +/- 0.6 days). These results suggest that partial clonal deletion of specific alloreactive cells achieved by this approach alone is insufficient to induce unresponsiveness to allografts in vivo.
Animals↗
Rates of release of subcutaneously injected antigens in the rat. Comparison of an aqueous preparation with two alum-precipated preparations.
Release of antigen E-125 I from the site of subcutaneous injection in male rats was delayed significantly when either of two alum-precipitated preparations containing 1.0-1.2 mg of Al/ml was administered rather than an aqueous preparation. The rates of 125I excretion were similarly influenced being statistically slower through the first week after single doses of the alum-precipitated preparations. The results of these studies strongly support the view that alum-precipitated vaccines offer more protection from system reactions than aqueous vaccines.
Absorption↗
The absorption of subcutaneously injected insulin.
Insulin has been used for the treatment of diabetes mellitus for 65 years. Still, little is known about the processes governing its absorption after subcutaneous injection. Since normoglycaemia is the general aim nowadays, knowledge about the absorption process is important. In this review, the physiology and the pharmacological and clinical factors influencing the absorption rate are dealt with, resulting in recommendations for the injection procedure of insulin.
Absorption↗
Undifferentiated sarcomas induced in Syrian hamsters by subcutaneous injection of diethylstilbestrol.
The carcinogenic effects of weekly subcutaneous injections of dimethylnitrosamine (NDMA: 0.05 of the LD50) and diethylstilbestrol (DES: 1.5 mg/kg body wt) or a combination of both carcinogens were studied in 64 Syrian hamsters. There was no additional tumorigenic effect on NDMA-induced liver tumours in hamsters which received DES treatment prior to NDMA treatment. In contrast to the previously reported DES effects, 72% of the DES-treated hamsters unexpectedly developed undifferentiated sarcomas around the interscapular injection site. This finding suggests a local carcinogenicity of DES, which might not be related to its hormonal effects.
Animals↗