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The latex allergen Hev b 5 transcript is widely distributed after subcutaneous injection in BALB/c mice of its DNA vaccine.

BACKGROUND: DNA vaccines reduce IgE responses to selected allergens, but severe reactions to the expressed antigen may limit the usefulness of the technique in allergen immunotherapy. OBJECTIVE: We sought to determine the extent of spread of an injected DNA vaccine in mice. METHODS: We placed the gene encoding the potent Hevea latex allergen Hev b 5 in a mammalian expression vector and injected this DNA vaccine subcutaneously into BALB/c mice. At several times after injection, the presence of Hev b 5 transcript was determined in multiple tissues by RT-PCR. The identity of the amplification product was confirmed by Southern hybridization and restriction analyses. RESULTS: Hev b 5 RNA appeared at the injection site and in the lymph nodes, spleen, and lungs within 1 day after injection and persisted for at least 14 days. Hev b 5 RNA was also identified in the blood and tongue 14 days after injection. Antibody and cell-mediated responses to Hev b 5 were also noted in the immunized animals at later time points. As expected, animals injected with the identical plasmid containing the Hev b 5 DNA in the antisense orientation mounted no immune response to Hev b 5. CONCLUSIONS: The rapid and widespread appearance of the Hev b 5 transcript in the injected mice confirms that DNA is translocated from the injection site, transcribed, and expressed in immune and nonimmune tissues after injection. Controlling the extent and degree of expression in specific target tissues may allow therapeutic DNA vaccination with plasmids that encode potentially toxic allergens.

Allergens↗

[Cutaneous symptoms after continuous subcutaneous injection of morphine].

We present two cases of patients who developed local swelling and induration after continuous subcutaneous infusion of morphine. Cutaneous complications of repeated subcutaneous injections of pentazocine, meperidine, ketobemidone and methadone are well described. There are few reports of similar reactions after subcutaneous administration of morphine. Both patients were later treated with sufentanil using the subcutaneous route without any reaction. Sufentanil might be an alternative to patients who cannot tolerate morphine.

Aged↗

Influence of human serum albumin content in formulations on the bioequivalency of interferon alfa-2a given by subcutaneous injection in healthy male volunteers.

To determine the influence of human serum albumin (HSA) content in formulations on the bioequivalency of recombinant interferon alfa-2a, a double-blind, randomized, two-way crossover study was conducted in 24 healthy male volunteers. Subjects received a single subcutaneous injection of 18 million IU of Roferon-A reconstituted with either the diluent containing 10 mg of HSA or the HSA-free diluent; final HSA contents in the 2 formulations were 15 mg and 5 mg, respectively. Administration of the 2 formulations resulted in similar 48-hour Roferon-A serum concentration-time profiles and comparable frequency and intensity of adverse events. The statistical analysis using the two one-sided tests procedure showed that both formulations were bioequivalent for pharmacokinetic parameters such as Cmax, tmax, AUC48, and AUC. We conclude that a threefold change in HSA content in formulations does not alter the bioequivalency of Roferon-A.

Adult↗

Therapeutic and protective effect of subcutaneous injections of L-364,718 on caerulein-induced acute pancreatitis.

The prophylactic and therapeutic effects of a potent cholecystokinin (CCK) receptor antagonist, L-364,718, on acute pancreatitis induced by caerulein were evaluated, analyzing morphologic and functional pancreatic parameters jointly. Edematous pancreatitis was induced by four subcutaneous injections of caerulein (20 micrograms/kg) in rats at 1-h intervals. Prophylactic administration of L-364,718 (0.1 mg/kg) prevented rise in serum amylase levels, interstitial edema, vacuolization, and impairment of pancreatic enzyme secretion that accompany caerulein-induced acute pancreatitis. After 7 days, a spontaneous regression of the morphologic alterations caused by caerulein-induced acute pancreatitis occurs; however, recovery of the secretory function of the pancreas was only reached after this period of time when L-364,718 was administered therapeutically (0.1 mg/kg/day). Prophylactically or therapeutically administered, L-364,718 exerts a beneficial effect on caerulein-induced acute pancreatitis, indicating that CCK (exogenous or endogenous) plays an important role in the development of this pathology.

Acute Disease↗

The effect of mixing human soluble and human crystalline zinc-suspension insulin: plasma insulin and blood glucose profiles after subcutaneous injection.

The effect of mixing human soluble insulin with two newly developed formulations of human crystalline zinc-suspension insulin was studied in two groups of 8 normal and 6 diabetic subjects. Mixing Human Actrapid with Human Ultratard and Humulin-S with Humulin-Zn, for 60 s before subcutaneous injection, significantly blunted the rise in free insulin levels (p less than 0.05) and the onset of action of the short-acting insulins (p less than 0.01). The loss of solubility that occurs on mixing these insulins, with the consequent loss of the rapid acting component, may diminish their therapeutic usefulness in the control of post-prandial blood glucose.

Adult↗

Subcutaneous injection with an insulin pen. Insulin absorption and plasma concentrations of glucose and free insulin.

In 6 type 1 diabetic patients treated with a basal-prandial injection regimen with a pen, plasma concentrations of free insulin and glucose were measured over a period of 24 h. We obtained an insulin peak 1 h after injection of regular insulin and lower levels at night. Between peaks, basal levels of free insulin were not reached. Glucose concentrations fluctuated only slightly. In 10 healthy volunteers, the absorption rate of insulin was studied after subcutaneous injection of 125I-Actrapid using a conventional technique and with a pen. During an 8-h period residual radioactivity and plasma insulin and glucose were measured. No significant differences were found, except for the insulin concentration 60 min after injection (higher after pen injection, P less than 0.05). The variability of the parameters was greater following pen injection (P less than 0.02). A basal-prandial injection regimen can thus produce stable glucose levels but only with considerable hyperinsulinaemia. Injection with an insulin pen causes a modest increase in absorption rate and plasma concentrations of insulin.

Absorption↗

Efficacy of levamisole pour-on compared with levamisole subcutaneous injection against Dictyocaulus viviparus infection in calves.

The efficacy of levamisole pour-on against Dictyocaulus viviparus was compared to that of subcutaneous levamisole injection. Eighteen calves were raised individually and artifically infected with D. viviparus larvae. Faecal samples were collected 27 and 28 days later and larvae per gram (l.p.g.) determined. The animals were then divided into three comparable groups. Group 1 animals remained untreated as controls. Group 2 animals received levamisole 10% w/v subcutaneous injection at a dose of 5 mg kg-1 and Group 3 received levamisole pour-on 20% w/v at a rate of 10 mg kg-1 applied transdermally. Results of l.p.g. measurements from faecal samples taken 7 and 8 days post-treatment indicated a dramatic reduction in the worm burden of animals in both treatment groups. Necropsies at 14 days post-treatment revealed few adult worms in these groups, indicating a 99 and 98% kill rate for pouron and subcutaneous injection, respectively.

Administration, Topical↗

Induction of sarcomas by a single subcutaneous injection of 7,12-dimethylbenz[a]anthracene into neonatal male Sprague-Dawley rats: histopathological and immunohistochemical analyses.

Animal experiments have shown that carcinogenicity of chemicals is higher in fetal or neonatal periods than adult. We investigated sensitivities to a carcinogen in peri-neonatal rats with a model of sarcomas-induction by a subcutaneous injection of chemo-carcinogen that has rarely done in neonatal rats. Neonatal male SD rats were injected with 7,12-DMBA 10, 100, and 500 microg, which resulted in sarcomas-induction in 0, 62, and 94% of rats. Male SD rats were injected with DMBA 500 microg at 0, 3, 7, 14, and 21 days, which resulted in sarcomas-induction in 94, 70, 64, 50, and 44% of rats. Although the induced sarcomas were occasionally in mixed morphological feature as previous reports for sarcomas of rat, each was immunohistochemically in almost monotonous pattern, and classification was feasible. The incidence of rhabdomyosarcomas was higher in rats neonatally injected with a higher dose of DMBA than a lower dose, and in rats injected at peri-neonatal periods than later periods. In histological observations for the site of injection before overt sarcomas develop, clusters of atypical mesenchymal cells emerged as previous studies, but also those were immunohistochemically differentiated into rhabdomyocytes and other mesenchymal cells. We consider these findings may contribute a little to elucidation of process of sarcomas-induction in rats.

9,10-Dimethyl-1,2-benzanthracene↗

Controlled test of anthelmintic activity of levamisole administered to calves via drinking water, subcutaneous injection, or alfalfa pellet premix.

A controlled test of the activity of 3 formulations of levamisole, at the dose level of approximately 8 mg/kg, against naturally occurring infections of gastrointestinal parasites and lungworms was made in 24 calves allotted to 4 groups of 6 calves each. Levamisole was administered to group I calves in the drinking water, to group II calves by subcutaneous injection, and to Group III calves by feeding alfalfa pellets mixed in corn silage; group IV calves were nontreated controls. Group I calves consumed the medicated water between 4 hours and 20 minutes and 9 hours and 40 minutes; group III calves consumed the medicated feed within 2 hours and 15 minutes. For calves of group I, II, and III, removals of 4th-stage Ostertagia sp were 64, 23, and 0%; of mature Ostertagia ostertagi, 90, 93, and 83%; and of mature Trichostrongylus axei, 92, 99, and 92%, respectively. For all 3 treated groups of calves, removal was 100% for 4th-stage Cooperia sp and for mature Trichostrongylus colubriformis, Cooperia oncophora, Cooperia punctata, and Oesophagostomum radiatum. Removals of Dictyocaulus vivipara were 90, 90, and 94% for calves of groups I, II, and III, respectively. There was no evidence of toxicosis. At necropsy, 2 calves in group II had small areas of edema at the sites of injection of levamisole.

Administration, Oral↗

Apparent interaction of dimethyl sulfoxide with cisplatin released from polymer delivery devices injected subcutaneously in dogs.

Local tissue toxicity, systemic toxicity and platinum pharmacokinetics were evaluated in 6 normal healthy beagle dogs injected subcutaneously with two formulations of a polylactide biodegradable polymer (Atrigel) system containing cisplatin. Dogs were injected 4 times at 30 day intervals at platinum dosages of 70, 105 and 157.5 mg/m2 (dose escalation). Once pharmacokinetics were established, 29 dogs with spontaneous stage IIb appendicular osteosarcoma were treated with 4 injections of the same polymer system containing cisplatin at 70 mg/m2 (20 dogs) and 100 mg/m2 (9 dogs) to establish efficacy against micrometastatic disease. Local tissue toxicity was variable. Systemic toxicity, as judged by clinicopathologic evaluation was not noted at any dose level or injection number. Interim (6 month) survival analysis revealed a median disease-free interval of 180 days. Consistent platinum release characteristics were found, however, the lack of toxicity and decreased disease-free-interval raised concerns over the biologic activity of the cisplatin. Prior to completion of the study, it was discovered that dimethyl sulfoxide, the solvent used in the co-polymer system, may be responsible for biologic inactivation of cisplatin. This was subsequently demonstrated in tissue culture assays. The clinical trial was suspended and dogs were treated with traditional chemotherapy.

Animals↗

Cell-specific expression of the alpha 1 (I) collagen promoter-CAT transgene in skin and lung: a response to TGF-beta subcutaneous injection and bleomycin endotracheal instillation.

Transgenic mice containing a rat collagen alpha 1 (I) promoter (3.6 kilobases) fused to the reporter gene chloramphenicol acetyl transferase (CAT) express the reporter gene parallel to endogenous gene in most connective tissues other than vascular tissue [Pavlin et al. (1992): J Cell Biol 116:227-236; Bedalov et al. (1994): J Biol Chem 269:4903-4909]. We have challenged transgenic mice with subcutaneous injections of transforming growth factor-beta (TGF-beta) or intratracheal instillation of bleomycin. In situ hybridization studies of skin revealed increased CAT expression in the papillary dermis of TGF-beta treated animals. In contrast, alpha 1 (I) collagen mRNA was expressed throughout the dermis including granulation tissue and reticular dermis. Therefore, the transgenic promoter responds to TGF-beta in a subset of dermal fibroblasts. Endotracheal instillation of bleomycin induces lung fibrosis which is thought to be mediated in part by TGF-beta. CAT gene expression in lungs was increased 6-8-fold at 2 weeks post bleomycin treatment. In situ hybridization studies revealed focal areas of cells expressing both CAT and collagen genes in the interstitium. However, most regions, especially around airways, contained a subset of cells expressing the endogenous gene with little or no CAT expression as judged by in situ hybridization. These cells could be myofibroblasts that require additional cis-acting elements to activate alpha 1 (I) collagen gene expression similar to smooth muscle cells.

Animals↗

[The diminishing oocyte toxicity following intraperitoneal infusion of cisplatin (CDDP) combined with subcutaneous injection of sodium thiosulfate (STS) in syngeneic young mice].

Small oocytes in 6-week-old C57BL/6 mice were destroyed in a dose-dependent fashion following intraperitoneal infusion of CDDP. ED65, the effective dose of which theoretically produced 65% destruction of small oocytes according to Probit analysis, was determined as 0.2mg/mouse. In this study, the oocyte toxicity induced with intraperitoneal treatment with CDDP (0.2mg) was offset by subcutaneous treatment with STS (40mg, 400 x molar ratio compared to that of CDDP). STS was subcutaneously injected into the back skin of mice at 60, 30, 15 minutes before, at the same time or at 15, 30, 60 minutes after the CDDP injection. STS markedly diminished the oocyte toxicity and reduced oocyte destruction about 45% when it was injected at 30, 15 minutes before or at the same time as CDDP infusion. On the other hand STS failed to reduce oocyte destruction when it was injected 15, 30 or 60 minutes later. STS might neutralize CDDP in the circulating blood to decrease the amount of active CDDP, but STS might not have any effect on CDDP once it is incorporated and conjugated with the DNA in the oocytes.

Animals↗

Experimental anterior uveitis after subcutaneous injection of feline sarcoma virus.

Feline sarcoma virus (FeSV) is a naturally occurring virus that causes spontaneous tumors in cats. The immunologic and morphologic characteristics of these tumors have been studied extensively. It was recently observed in experiments undertaken to induce systemic malignancy with this virus, that severe uveitis and clinical blindness occurred. An investigation of the ophthalmologic changes was undertaken. A fulminent anterior uveitis was produced in cats by a series of subcutaneous injections of live FeLV-FeSV. This intraocular inflammation occurred in five of six animals using high viral titers, and four of seven with lower titers, resulting from the freeze thaw process. On histopathologic examination, most animals demonstrated dysplastic changes of the ciliary body in addition to the iridocyclitis. The remainder of the eye was unaffected. These animals developed systemic tumors unaccompanied by local inflammation, many of which spontaneously regressed. Notable features of this potential model for uveitis are that (1) direct injection into the eye is unnecessary, and (2) intravenous administration inducing immune tolerance with antigenic overload presented to the spleen is avoided. This inflammatory reaction seems to be specific to the iris and ciliary body. Levels of live virus detected in the aqueous humor exceeded those in the serum. These results suggest that the virus may be actively secreted by the ciliary epithelium, or may preferentially proliferate within the eye.

Animals↗

Changes in the prevalence of resistant Escherichia coil in cattle receiving subcutaneously injectable oxytetracycline in addition to in-feed chlortetracycline compared with cattle receiving only in-feed chlortetracycline.

Information about the prevalence of antibiotic resistance in commensal enteric bacteria is of interest because these bacteria are potential indicators of selection pressure on enteric bacteria and represent a reservoir of resistance genes in potentially pathogenic bacteria. This study reports changes in the prevalence of resistance to antibiotics in commensal Escherichia coli from cattle receiving either subcutaneously injectable oxytetracycline in addition to in-feed chlortetracycline or only in-feed chlortetracycline. Resistance to 19 antibiotics was examined. The use of injectable oxytetracycline in addition to in-feed chlortetracycline was significantly associated (P < 0.05) with an increase in the prevalence of resistance only to chloramphenicol and sulfisoxazole.

Animals↗

Subcutaneous injections of apomorphine, stimulus generalization and conditioning: serious pitfalls for the examiner using apomorphine as a tool.

This report shows that stimulus generalization occurs in rats conditioned by a single injection of apomorphine. The data suggest that apomorphine initially acts as an unconditioned stimulus (UCS) of an unconditioned response (UCR) that, in turn, produces stimuli which become conditioned stimuli (CS) of a conditioned response (CR) having a nature identical to that of the UCR. The study also shows that behaviour elicited by a subcutaneous injection of apomorphine depends on the part of the body selected for administration. The mentioned properties should be taken into account when apomorphine is used as a tool in studies on brain and behaviour.

Animals↗

Plasma concentrations and urinary excretion of histamine after inhalation and subcutaneous injection of histamine.

1. Increased histamine concentrations are found in the plasma and urine following allergen challenge in allergic subjects. This study compared a controlled challenge with clinically relevant doses of inhaled and injected histamine, as indicative of an allergic response, in an attempt to validate the use of urinary histamine or 1-methylhistamine measurements as an objective, non-invasive diagnostic test. 2. Inhalation of histamine produced peripheral vasodilation, increased heart rate, a fall in partial expiratory flow rate (pEFR) and blood pressure, 'tight chest' and cough. Subcutaneous injection produced vasodilation and headache but no change in heart rate or blood pressure. 3. Plasma histamine concentrations were similar in the two studies. Inhalation of increasing doses of histamine through a nebuliser (output 0.13 ml min-1) resulted in an increase from a mean of 0.30 to 1.65 ng ml-1, with return towards baseline within 20 min. Injection of 1 mg histamine s.c. produced an increase from 0.32 to 1.4 ng ml-1 within 5 min, remaining above 1 ng ml-1 for 30 min. 4. There was a significant increase of 15.2 ng mg-1 creatinine in urinary histamine concentration following the injection of histamine (P = 0.04) and an increase of 11.4 ng mg-1 creatinine when histamine was given by inhalation (P = 0.18). Histamine excretion rate increased by 108 ng min-1 (P = 0.04) after inhalation and by 37.2 ng min-1 (P = 0.09) after injection. Urinary 1-methylhistamine concentrations were significantly raised following both histamine inhalation (+ 238 ng mg-1 creatinine; P = 0.013) and injection (+ 180 ng mg-1 creatinine; P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

Repeated subcutaneous injection of staphylococcal enterotoxin B-stimulated lymphocytes retains epidermal thickness of psoriatic skin-graft onto severe combined immunodeficient mice.

Several approaches have recently been carried out to attempt to establish a mouse transplantation model of psoriasis. To study the effects of superantigen-driven peripheral blood mononuclear cells (PBMCs) on the persistence of psoriasiform epidermis and cytokine gene expression of the grafted psoriatic skin, staphylococcal enterotoxin B (SEB)-stimulated PBMCs (SEB-PBMCs) from psoriatic patients were subcutaneously injected once or repeatedly under the grafted full-thickness involved psoriatic skin onto severe combined immunodeficient (SCID) mice. After 5 weeks, the persistence of a psoriasiform epidermis was most distinct in mice with repeated injection of SEB-PBMCs. E-selectin expression was observed on endothelial cells in the upper dermis in mice with repeated injection of both SEB-stimulated and unstimulated PBMCs, while mice with single injection of unstimulated or SEB-PBMCs did not show positive staining. Both interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) mRNA were detected after 5 weeks, only in mice with repeated injection of SEB-PBMCs. It is concluded that continuous supply of the activated PBMCs may help the persistence of psoriasiform architecture more clearly, and that this transplantation mouse model may serve as an in vivo model for the study of the pathogenesis and therapy of psoriasis.

Adult↗

What happens if intradermal injections of rabies vaccine are partially or entirely injected subcutaneously?

Reported are the results of a study with the Thai Red Cross two-site intradermal purified Vero-cell rabies vaccine (PVRV) schedule that was deliberately injected into subcutaneous tissue. The 44 healthy nonimmune Thai adults who were enrolled in the study were randomly assigned to the following groups and given PVRV as shown: group A (two intradermal injections on days 0, 3, and 7); group B (one intradermal and one subcutaneous injection on days 0, 3, and 7); and group C (two subcutaneous injections on days 0, 3, and 7). Neutralizing antirabies antibody titres were determined on day 14 using the rapid fluorescent focus inhibition test. High rabies antibody titres were obtained for all three groups. These results suggest that the economical and safe Thai Red Cross intradermal PVRV regimen could be used in selected general health care facilities.

Adolescent↗