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The acute toxicity of allyl chloride by subcutaneous injection in mice.

Male ICR mice were administered allyl chloride at dose of 496 mg/kg, 600 mg/kg, 720 mg/kg, 864 mg/kg or 1037 mg/kg by a single subcutaneous injection. Sixteen of 25 mice died by the 7th day after the injection and LD50 was calculated 621 mg/kg body weight (95% C.I.: 522-739 mg/kg). A marked congestion with severe hemorrhage and edema were observed in the lung. Liver and kidney damages were also found, and these were characterized by the dilated sinusoids, degenerative change of hepatic cells, and focal necrosis in the liver; and necrosis of epithelium in convoluted tubules of the kidneys. Nine mice have survived by the 7th day after the injection and all of them showed a various degree of damages in the testes. The testicular lesions could be classified into two types. One type of the lesion was characterized by degeneration and exfoliation of germ cells, appearance of polynuclear giant cells in the seminiferous tubules, and mild proliferation of Leydig cells in the interstitium. In another type of the lesion, all type of cells in tubules, including Sertoli cells, and Leydig cells became necrotic. This is the first study reporting the testicular toxicity of allyl chloride.

Allyl Compounds↗

A comparison of three mathematical models to describe the disappearance curves of subcutaneously injected 125I-labelled insulin.

1. The absorption of insulin in constant and varied volumes and concentration was studied in healthy volunteers. 2. Disappearance curves of radioactivity after subcutaneous injection of labelled insulin were fitted with three models: a diffusion rate-limited, a dissolution rate-limited and a capacity-limited model. 3. For each curve and model goodness of fit (r2) and sum of weighted squared deviations (SWSD) were calculated. With constant volume and concentration r2 was greater than 0.097 for each curve. SWSDs with the second model were less than those with the first (NS) and third (P less than 0.01). 4. When volume and concentration were varied, the parameters of the first and third model also varied, arguing against the validity of these models. 5. It is concluded that each of the three models, although yielding an accurate description of the observed data is too simple conceptually. Suggestions for more appropriate modelling are discussed.

Absorption↗

Comparison of subcutaneous injection and high-dose inhalation of epinephrine--implications for self-treatment to prevent anaphylaxis.

The plasma concentrations of epinephrine were determined in healthy subjects administered epinephrine by subcutaneous injection of 0.5 mg or inhalation of 1.5 to 4.5 mg (10 to 30 inhalations from a metered-dose aerosol). The absorption of injected epinephrine was variable and in several cases very slow. The individual maximum values for epinephrine in plasma were 4.65 +/- 1.09 (range 0.74 to 8.31) nmol/L, and these maxima were attained 5 to 120 minutes after injection. Inhaled epinephrine was rapidly and dose dependently absorbed. Ten inhalations resulted in 2.72 +/- 0.84 (0.75 to 5.67) nmol/L within 5 minutes and 20 inhalations resulted in 7.19 +/- 1.78 (2.10 to 13.83) nmol/L with rapid increases and maxima within 20 minutes in seven of eight subjects. Gastrointestinal side effects were dose limiting when epinephrine was administered by inhalation. Our results indicate that inhalation of 2 to 3 mg of epinephrine produces rapid increases of epinephrine concentrations in plasma to levels that have previously been demonstrated to counteract bronchoconstriction induced by inhaled allergen in subjects with asthma. Inhalation has several advantages over injection for self-administration of epinephrine, e.g., in patients who are allergic to insect (Hymenoptera) stings. Apart from the absorption being more rapid, the locally high concentrations of epinephrine in the airways should be advantageous, since bronchoconstriction is one of the life-threatening phenomena of the anaphylactic reaction. This route of administration is also simple for the patient.

Administration, Inhalation↗

Comparison of Edmonston-Zagreb and Schwarz strains of measles vaccine given by aerosol or subcutaneous injection.

The serological response to measles vaccine was tested in Bangladesh in groups of infants aged 4-6 months who received equal doses of Edmonston-Zagreb or Schwarz vaccine by subcutaneous injection or by aerosol. Seroconversion (as measured by the haemagglutination test) occurred in 62% of infants receiving Edmonston-Zagreb strain by injection compared with only 37% of those receiving Schwarz strain. Seroconversion occurred in 35% of those given Edmonston-Zagreb and 34% of those given Schwarz vaccine by aerosol. Edmonston-Zagreb strain appears more effective than Schwarz vaccine in this population and further studies are indicated in other populations where early measles immunisation is desirable.

Aerosols↗

Effects of subcutaneously injected graded doses of all-trans retinoic acid and all-trans retinoyl beta-glucuronide on the outcome of pregnancy in Sprague-Dawley rats.

The effects of single subcutaneous injections (s.c.) of graded doses (20, 40, 80, 160, 320, and 480 mumol/kg body weight (BW) of all-trans retinoic acid (RA) and all-trans retinoyl beta-glucuronide (RAG) on day 8.5 of gestation on the outcome of pregnancy in Sprague-Dawley rats was studied. At dose levels of 20, 40, and 80 mumol/kg BW, neither RA nor RAG showed any adverse maternal or fetal effects. However, at dose levels of 160, 320, and 480 mumol/kg, RA was found to be much more toxic than RAG to both mother and fetus. Fetuses of animals receiving a 160 mumol/kg BW dose of RA were significantly reduced in weight and length, while animals receiving the same dose of RAG had fetuses of normal size. RA doses of 320 and 480 mumol/kg BW resulted in symptoms of maternal toxicity and even death. In contrast, RAG at these high levels produced no signs of maternal toxicity. RAG doses of 320 and 480 mumol/kg BW were also less toxic to fetuses. RA doses of 320 mumol/kg BW resulted in only 8% live births, while animals treated with an equivalent amount of RAG experienced 95% live births. Animals receiving a dose of 480 mumol/kg BW of RA had no live births, but similar doses of RAG resulted in 28% live births and pups of normal size.

Animals↗

Central venous catheter with subcutaneous injection port (Port-A-Cath): clinical experience with children.

Long-term intermittent venous access was established in 26 children by means of a central venous catheter (CVC) with a subcutaneous injection port (Port-A-Cath) (PAC). As of December, 1985, PACs had been in place for 20-750 days (cumulative 10,890 days) with 647 entries into the system. The PACs were used for blood sampling and administration of chemotherapy, antibiotics, fluids, total parenteral nutrition (TPN), and blood products. One patient with sever neutropenia (absolute neutrophil granulocyte count [ANC] less than 0.1 x 10(9)/L) at the time of the PAC implant developed an infection around the port after 2 days, with subsequent septicemia (Bacillus cereus) necessitating removal of the PAC. Otherwise, no definite PAC-related infections occurred, including 258 days of neutropenia (ANC less than 0.5 x 10(9)/L). Two PACs were found occluded with greyish deposits of fat and organic material after long-term (45 and 61 days) continuous TPN and were removed. Malposition of catheter, extravasation, thrombosis, and other potential technical or psychological complications were not observed. The children continued normal activities, and the easy venous access decreased emotional stress during treatment. Local doctors were trained to use the PACs, with which they administered maintenance chemotherapy. We conclude that the use of PACs in children is safe, even in the first year of life, and has many advantages when compared with other CVCs currently in use. Strict indications, meticulous implantation technique, and adequate handling are, however, mandatory.

Adolescent↗

Absorption rates of subcutaneously injected insulin in the dog as calculated from the plasma insulin levels by means of a simple mathematical model.

The appearance rate of insulin (calculated insulin secretion rate) in the circulating blood after subcutaneous injection was estimated in diabetic dogs from serial measurements of immunoreactive insulin concentrations using a simple mathematical model based on the insulin half-life and the distribution space. In the case of highly purified monocomponent porcine insulin, maximum concentrations occurred after 30-60 min. The duration of insulin appearance was dose-dependent and the rate of appearance could be described by a bi-exponential function. It was linearly dose-dependent but the effect on glycaemia showed saturation kinetics. The action of the injected dose on the fasting glycaemia diminished when the appearance rate became less than 0.3 mU X kg-1 X min-1. Fractional dose recovery was between 70% and 90% and was not different between depot and regular insulin. Appearance kinetics were not significantly affected by the initial glycaemia. The model presented provides a means for quantitative characterization of different insulin preparations.

Absorption↗

Central venous catheter with subcutaneous injection port (Port-A-Cath): 8 years clinical follow up with children.

Long-term intermittent venous access was established in 77 children by means of a central venous catheter (CVC) with a subcutaneous injection port (Port-A-Cath; PAC). Seventy of these children were included in this follow-up study. Sixty-three were treated for different malignant diseases, five for cystic fibrosis, one for severe hemophilia and one for central nervous system disease with seizures as the main problem. As of April, 1992, PACs had been in place for 3/12 to 8 3/12 years (cumulative 175 5/12 years) with 2,206 entries into the system. The PACs were used for blood sampling and administration of chemotherapy, antibiotics, fluids, total parenteral nutrition (TPN) and blood products. Portal infection was observed in four patients of which two patients had their PAC removed. Catheter dislocation was observed in two and catheter breakage in one. Portal occlusion, extravasation, thrombosis leading to removal of the PAC or other technical or psychological complications were not observed. The children continued normal activities, and the easy venous access decreased emotional stress during treatment. Local doctors were trained to use PACs, through which they administered maintenance chemotherapy. We conclude that long-time use of PACs in children is safe and has many advantages compared to traditional CVCs in use. Strict indications, meticulous implantation techniques and adequate handling are, however, mandatory.

Adolescent↗

[Effects of subcutaneous injection with different doses of ginseng on the rat model of chronic Pseudomonas aeruginosa pneumonia].

OBJECTIVE: To observe the effect of ginseng extracts on a rat model of chronic Pseudomonas aeruginosa (PA) pneumonia. METHODS: Subcutaneous injection with four different doses of ginseng aqueous extracts to the model rats for two weeks. RESULTS: Milder macroscopic lung pathology and lower incidence of lung abscesses were found in all the four groups received different doses of ginseng treatment compared to the control group (P < 0.05). Histopathology of the lungs was negatively correlated with the ginseng doses (r = -0.95, P < 0.01). The mast cell number in the lung foci in group I, II and IV was significantly lower than that in the control group (P < 0.05). Bacterial clearance in group II and group III was enhanced significantly (P < 0.05) compared with that in the control group. The specific antibody responses were down-regulated in group II, III and IV (P < 0.01), and IgM level in group I was lower compared to the control group (P < 0.01). Serum IgM level was positively correlated with the ginseng doses (r = 0.93, P < 0.05). IgG2a titer in group I was higher than that in the control group (P < 0.05). Serum IgG2a level was positively correlated with the ginseng doses (r = 0.90, P < 0.02). Two weeks after PA lung infection, the serum level of IgG against PA, aeruginosa alginate in group I, II, and III was higher than that in the control and group IV (P < 0.05), and the anti-alginate IgA level in group I, III and IV was lower than that in the control (P < 0.05). CONCLUSIONS: The ginseng dose of 2.5 mg/kg was the best dosage in the present study, and it showed an effect of stimulating T helper type I response.

Animals↗

Magnesium sulphate subcutaneously injected protects against kainate-induced convulsions and neurodegeneration: in vivo study on the rat hippocampus.

Kainate, an agonist of a unique subclass of glutamate receptors (kainate receptor), was injected intracerebroventricularly in rats to induce convulsive reactions and hippocampal damage in order to model glutamate-mediated brain injury. Rats treated with magnesium sulfate (subcutaneously injected, up to 600 mg/kg) were found to be protected from kainate neurotoxicity depending on the dose and time of application. Results were largely consistent with those obtained previously by using quinolinate as an excitotoxic N-methyl-D-aspartate-receptor agonist. Magnesium is discussed as being a natural and relatively safe therapeutic in cases of glutamate-induced (hypoxic, ischemic, traumatic, or convulsive) disorders of the brain.

Animals↗

Acute inflammation in foetal and adult sheep: the response to subcutaneous injection of turpentine and carrageenan.

Because of the small number of inflammatory cells found in skin wounds, it has been considered that foetal sheep are incapable of an adequate inflammatory response. The present study shows that subcutaneous injection of turpentine or carrageenan into foetal sheep consistently excites a severe cellular inflammatory reaction. At 75 days gestation the inflammatory cells are all macrophages. As the foetus develops, polymorphs play an increasing role in the early response to turpentine. By 120 days inflammatory cells are almost all polymorphs as in adult sheep. However the response to carrageenan remains macrophage in type. At all stages of gestation the acute cellular response is followed by development of scar tissue, more pronounced with turpentine than carrageenan. Any proposed intrauterine surgery must allow for the pronounced and prolonged inflammatory response and scar tissue formation caused by persistent inflammatory stimuli in foetal animals.

Animals↗

Serum group I pepsinogens and gastrin in relation to gastric H+ and pepsin outputs before and after subcutaneous injection of pentagastrin.

A conventional pentagastrin test was carried out in 25 patients with dyspeptic complaints, and gastric H+ and pepsin outputs were determined. Blood was drawn before the intubation and 5 and 30 min after subcutaneous injection of pentagastrin, and serum group I pepsinogens (PG I) and serum gastrin were determined by radioimmunoassay methods. A significant correlation was found between serum PG I, on the one hand, and basal gastric pepsin, output as well as pentagastrin-stimulated gastric H+ and pepsin outputs, on the other. Basal serum gastrin was also significantly correlated to pentagastrin-stimulated gastric pepsin output as well as to serum PG I. Pentagastrin failed to induce an increase in serum PG I during the first 30 min.

Adult↗

Massage-induced release of subcutaneously injected liposome-encapsulated drugs to the blood.

Liposome-based, externally regulated drug delivery system is described in which liposome-encapsulated bioactive molecules can be delivered into the blood in response to simple mechanical action. Without any mechanical stimulation, subcutaneously injected 200 mm liposomes are usually trapped in the interstitial for prolonged time. However, upon lymphotropic stimulation (such as manual massage of the injection site), the liposomes can be mobilized into the blood via lymphatic pathway. Up to 40% of the injection dose can be delivered to the blood via lymphatic pathway from the injection site at the rabbit's front paw dorsum during 5 min manual massage cycle. Using vasoconstricting hormone angiotensin II as liposome-encapsulated pharmacological marker, we demonstrated that physiological response to encapsulated drug (average blood pressure increase) can also induced and modulated by massage. Massage itself was found to have no effect on the blood pressure. Modification of liposome surface with polyethylene glycol was found to increase blood localization of the liposome-encapsulated drug presumably due to decreasing the uptake of the drug carrier by lymph node macrophages. Pressure-dependent gaps between lymphatic capillary endothelial cells are thought to play the role of the size discrimination device allowing larger particulates into the lymphatics and, eventually into the blood after increase of interstitial pressure caused by injection site massage.

Angiotensin II↗

Subcutaneous injection of 99mTc pertechnetate at acupuncture points K-3 and B-60.

The acupuncture points are known to be morphologically related to the nerves and vessels. Yet the physiological role of blood vessels in the formation of acupuncture points remains unknown. With subcutaneous injection of 99mTc pertechnetate at the acupuncture points K-3 and B-60 and with intra-acupuncture point injection of 99mTc pertechnetate at K-3 and B-60, a lower-limb venography like what was obtained by intravenous injection of 99mTc macroaggregated albumin was demonstrated in the present study. It seems that some acupuncture points do play a role in drainage of tissue fluid from soft tissue into the veins.

Acupuncture Points↗

Pharmacokinetics and pharmacodynamics of a low molecular weight heparin (enoxaparin) after subcutaneous injection, comparison with unfractionated heparin--a three way cross over study in human volunteers.

We determined, in volunteers, the plasma levels of heparin above and below the critical chainlength necessary for thrombin inhibition (ACLM and BCLM), from 1 to 24 h after subcutaneous injection of 5000 IU unfractionated heparin (UFH), 40 mg enoxaparin and 1 mg/kg body weight of enoxaparin (LMWH) (n = 12 for each dose). The levels were calculated from the antithrombin- and anti-Xa activities using the specific activities of the materials injected. We also determined the course of thrombin- and of factor Xa generation after triggering the extrinsic system in the same samples. From the thrombin generation curves, we calculated the course of prothrombinase activity. When the ACLM and BCLM plasma-levels are plotted against the inhibition of thrombin- and factor Xa generation, it appears that: a) There is a unique dose response relationship between ACLM level and the inhibition of thrombin generation, independent of whether the ACLM is derived from UFH or LMWH. This relationship is not significantly altered by the BCLM appearing after LMWH injection. b) There is a similar unique relationship between ACLM level and the inhibition of factor Xa generation, again independent of BCLM. c) Inhibition of prothrombin activation hardly contributes to the overall effect on thrombin formation and is again independent of the source of ACLM. d) ACLM levels were significantly higher after injection of LMWH than after UFH injection, even though the amounts of ACLM injected with the highest dose of LMWH were smaller than those administered in the UFH injection. We conclude that the only functional difference between LMWH and UFH is the much higher bioavailability of the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Intermittent subcutaneous injections of pain medication: effectiveness, manageability, and satisfaction.

This study describes the use of intermittent subcutaneous injections of medications for pain control in a home hospice program. Six questionnaires were used to collect data over a one-year time period on the 52 patients who received medications by this route. Eighty-four percent of those patients had a diagnosis of cancer; patients received hospice care for a mean of 25 days. On average, intermittent subcutaneous medications were instituted three days prior to the patient's death. The main indication for this route was difficulty swallowing. Morphine was the most frequently used drug; side effects from the medication and problems with the route were rarely reported. Demographic information was collected on both the nursing staff and patients' caregivers; analysis indicated that caregivers were able to manage the injections and were satisfied with the method. Assessment of pain prior to and following the injections demonstrated the effectiveness of this method in controlling patients' pain.

Adult↗

Monitoring local disposition kinetics of carboplatin in vivo after subcutaneous injection in rats by means of 195Pt NMR.

The anticancer drug carboplatin has been monitored in rats during treatment by means of in vivo 195Pt NMR spectroscopy at 2.0 T. The purpose of the study was to assess local disposition kinetics in intact tissue following subcutaneous injection of a platinum-containing drug. Serial 195Pt NMR measurements have been carried out in four animals after administration of carboplatin solutions with doses ranging from 37.1 to 59.4 mg per kg body weight. A surface coil of 2 cm diameter tuned to 18.3 MHz was placed over the injection site (back of the neck of the animals). To optimize measurement parameters of the single-pulse-acquire sequence and to determine chemical shifts and the detection threshold, in vitro 195Pt NMR experiments have been performed on model solutions of potassium tetrachloroplatinate(II), carboplatin, and cisplatin with different solvents such as H2O, DMSO, and DMF. Resonances of PtCl2-4, carboplatin, cisplatin, and cis-[Pt(NH2)Cl(DMSO)]+ were observed at chemical shift positions delta = -1623 ppm, -1705 ppm, -2060 ppm (cisplatin in DMSO), and -3120 ppm, respectively, relative to the reference signal of Na2PtCl6 at delta = 0 ppm. A spin-lattice relaxation time of carboplatin of T1 = (0.103 +/- 0.02) s was measured. The threshold for NMR detection of platinum-containing compounds estimated from the in vitro experiments was 10 micromol (corresponding to approximately 4.8 mM). In vivo 195Pt NMR spectra obtained in four rats after administration of carboplatin showed a broad resonance at delta = -(1715 +/- 8) ppm. The signal-to-noise ratio of this peak (starting 2 min after the injection) was approximately 9:1 for a measurement time of 6 min (TR= 13 ms, 28672 transients). The elimination rate constant of local disposition of carboplatin was kel = 0.017 (0.008-0.025) min-1 (median and range).

Animals↗