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PubMed1999

DNA immunization by intramuscular injection or gene gun induces specific IgG antibodies against a Schistosoma japonicum 22 kDa antigen, Sj22, when fused to the murine Ig K-chain secretory leader sequence.

The 22 kDa tegumental surface membrane-associated antigen of Schistosoma japonica, Sj22, is of recognized interest in schistosomiasis vaccine research. However, previous attempts to induce antibody responses against Sj22 by DNA immunization have been unsuccessful. In this report we demonstrate that fusing the Sj22 cDNA to the murine immunoglobulin Ig kappa-chain secretory leader sequence results in the generation of antigen-specific IgG antibodies following DNA immunization. Mice were immunized into the skin with DNA-coated gold microspheres using a gene-gun, or into the quadriceps muscle by intramuscular injection. Both methods of delivery generated antigen-specific IgG antibodies against the 22 kDa schistosome antigen. The use of a secretory leader sequence, such as the murine Ig-kappa chain used in this study, may facilitate the induction of host antibody responses following DNA immunization with other parasite cDNAs.

Animals↗
PubMedDate not supplied

[Comparison of oral administration and intramuscular injection of thymus preparations on the leukopoiesis test in rats and some of the preventive possibilities emerging from the results].

Considering the fact that all immunologic processes consume energy, we have been attempting for more than a decade to combine immunostimulating measures with such for increasing the energetic state. This basic resulted in designing several modern variants of the Oxygen Multistep Immunostimulation. In order to make this method broadly applicable to public health care, its protocol had to be simplified in such a way that it can easily be applied also to outpatients at a reasonable expenditure of time. Such a program is described here among other variants. Its concept is based on measurements of leukopoiesis in rats after administration of thymus extract. The test system used revealed that oral administration of the thymus extract taken from specified dragées was of at least the same effect as intramuscular injection. The simplified variant of the Oxygen Multistep Immunostimulation which can be practised ambulantly within a short time, consists of the administration of thymus dragées and the 15-min-oxygen multistep quick procedure of the Oxygen Multistep Therapy. It is demonstrated by comparison of photographs of a case report the precancerous skin lesions can be unprimed by this simple treatment within 10 months. The finding indicates that along these lines a permanently effective cancer prevention might become practicable. Furthermore, it is supposed that the simple treatment schedule described should be of benefit in preventive medicine and gerontology as well, in order to fight illness in general and to reduce the disposition to diseases having a bad prognosis particularly in old age.

Administration, Oral↗
PubMed2001

On the fate of plant or other foreign genes upon the uptake in food or after intramuscular injection in mice.

Uptake and persistence of the DNA of bacteriophage M13 and the cloned gene for the green fluorescent protein (GFP) as test genes for food-ingested DNA have previously been traced from the intestinal contents, via the gut wall, Peyer's patches and peripheral white blood cells to spleen and liver, and via the placenta to fetuses and newborn animals. We have now chosen a natural scenario and fed soybean leaves to mice. The distribution of the plant-specific, nucleus-encoded ribulose-1,5-bisphosphate carboxylase (Rubisco) gene has been studied in the mouse. The Rubisco gene or fragments of it can be recovered in the intestine from 2 h up to 49 h after feeding, and in the cecum up to 121 h after ingestion. Thus, plant-associated, naturally fed DNA is more stable in the intestinal tract than naked DNA. Rubisco gene-specific PCR products have also been amplified from spleen and liver DNA. There is no evidence for the expression of orally administered genes, as assessed by the RT-PCR method. Moreover, mice have been continuously fed daily with GFP DNA for 8 generations and have been examined for the transgenic state by assaying DNA isolated from tail tips, occasionally from internal organs of the animals, by PCR. The results have been uniformly negative and argue against the germline transfer of orally administered DNA. Upon the intramuscular injection of GFP DNA, authentic GFP DNA fragments have been amplified by PCR from DNA from muscle for up to 17 months post-injection, and from DNA from organs remote from the site of injection up to 24 h post injection. GFP fragments can also be retrieved from the intestinal contents up to 6 h post injection. The organism apparently eliminates injected foreign DNA via the liver-bile-intestinal route.

Animals↗
PubMed2001

Solvent/detergent treatment does not alter the tolerance or uptake of human normal immunoglobulin for intramuscular injection.

BACKGROUND AND OBJECTIVES: The tolerability and pharmacokinetics of a solvent/detergent-treated intramuscular immunoglobulin were compared with those of the standard product. MATERIALS AND METHODS: Single, 750-mg intramuscular (i.m.) injections were administered to a total of 36 healthy individuals: 23 in a double-blind trial and 13 in an open trial. Changes in specific serum hepatitis A and hepatitis B antibodies were monitored for a period of up to 3 months postinjection. RESULTS: No serious adverse reactions were reported, and the bioavailability of the solvent/detergent-treated preparation was equivalent to that of the standard i.m. immunoglobulin. CONCLUSION: There is no evidence that solvent/detergent treatment alters the pharmacokinetics or tolerance of human normal immunoglobulin, but it offers additional assurance against potential virus transmission.

Adolescent↗
PubMed1987

Single intramuscular injection of aztreonam in the treatment of uncomplicated gonorrhoea in women.

A total of 225 female patients with uncomplicated gonorrhoea was treated at random with either a single intramuscular injection of 1 g aztreonam or with 2.4 mega units procaine penicillin intramuscularly plus 1 g probenacid orally. Patients were followed up at 1, 2 and 3 weeks for bacteriological tests. The success rate among 101 of 116 patients on aztreonam who attended at least 1 follow-up examination after treatment was 100%, including 11 cases with penicillinase-producing N. gonorrhoeae. The minimum inhibiting concentrations of aztreonam in vitro were very much lower than the serum concentration, all strains being sensitive at 0.5 micrograms/ml or less. In a comparative group of 109 women treated with penicillin, there were 11 failures (penicillinase-producing N. gonorrhoeae strains) in 98 women who were followed-up. Aztreonam was well tolerated and there were no side-effects.

Aztreonam↗
PubMed1986

Bioavailability in rats of human recombinant tissue plasminogen activator after subcutaneous and intramuscular injection.

The bioavailability of human recombinant tissue plasminogen activator (rt-PA) in rats was measured after subcutaneous (s.c.) and intramuscular (i.m.) injection. Rt-PA was absorbed after both i.m. and s.c. injection, giving peak plasma concentrations within 30 min and 1 h, respectively, with detectable concentrations up to 6 h. These peak values of bioavailable t-PA were obtained in a functional fibrin plate assay of euglobulin precipitates and expressed as +88% and +243% (for s.c. and i.m. routes respectively) above basal rat fibrinolytic activity. Prior injection of rt-PA, s.c. or i.m., significantly reduced the weights of thrombi induced in the inferior vena cava after injection.

Animals↗
PubMed2003

Intramuscular injection of naked plasmid DNA encoding human preproinsulin gene in streptozotocin-diabetes mice results in a significant reduction of blood glucose level.

The insulin complement with gene therapy has been used as an experimental treatment for insulin dependent diabetes (IDDM). In the present study, we constructed naked plasmid DNA vector encoding recombinant human preproinsulin gene (pCMV-IN), and injected the plasmids (100 microg/mouse) intramuscularly combined with electroporation, to achieve the in vivo transfer of insulin gene in streptozotocin (STZ)-induced diabetic C57 mice. The expression of vector-derived insulin mRNA was detected with RT-PCR in transfected local skeletal muscles. The plasma insulin was elevated significantly in pCMV-IN injected diabetic C57 mice, which was complemented to the level similar to the intact normal control. The protein expression lasted for at least 35 days after the plasmid injection. Gene therapy with pCMV-IN plasmids considerably decreased the blood glucose level in STZ-induced diabetic mice from d 7 to d 35 by about 6 mmol/L. The gene therapy also reduced the mortality of severe diabetic mice significantly from 100% to 37% at the 6th week. Our results indicate that the direct intramuscular injection of naked plasmids encoding human preproinsulin gene achieves the effective expression of insulin. The restoration of insulin decreases blood glucose and increases the survival in severe diabetic mice. The gene therapy might be provided as a practical therapeutic approach to IDDM.

Animals↗
PubMed1983

Local muscle damage and oily vehicles: a study on local reactions in rabbits after intramuscular injection of neuroleptic drugs in aqueous or oily vehicles.

The local muscle damaging effect of a series of neuroleptics formulated in water or in oily vehicles (Viscoleo, sesame oil, methyl oleate or squalane) has been investigated after intramuscular injection in rabbits. Each drug preparation (2 ml) was administered intramuscularly in the central part of the longissimus dorsi muscle of four rabbits. The rabbits were killed three days after the injection, and the injection site was examined macroscopically. Areas of necrotic muscle tissue were isolated by dissection and weighed. All preparations in aqueous solution caused local muscle damage (large necrotic area) at the injection site. This effect was almost completely neutralized by the Viscoleo vehicle. The sesame oil, methyl oleate and squalane vehicles also neutralized the local damaging effect, but not to the same extent as that of the Viscoleo vehicle.

Animals↗
PubMed1978

Serum and plasma concentrations of clindamycin following a single intramuscular injection of clindamycin phosphate in maintenance haemodialysis patients and normal subjects.

Serum levels of clindamycin bioactivity and total clindamycin were studied after single intramuscular injections of 300 mg of clindamycin phosphate in a group of 6 normal subjects and a group of 6 maintenance haemodialysis patients. The patients were studied during a non-dialysis period and then again during haemodialysis. Peak levels tended to be higher and elimination half-lives shorter in the patients than in the normal subjects. Possible reasons for these differences are discussed. There was no evidence that haemodialysis per se influenced the pharmacokinetics of clindamycin phosphate. The proportion of unhydrolysed clindamycin phosphate tended to be higher in the renal failure patients and the reason for this is not apparent. Little, if any, dosage modification is necessary in severe renal fialure although there is probably little point in exceeding a dose of 300 mg intramuscularly every 5 h even in severe infections in patients with severe renal failure. The higher peak levels in patients with advanced renal failure indicate the need for further studies with repeated doses.

Adult↗
PubMed1995

Pharmacokinetics of methotrexate after intravenous and intramuscular injection of methotrexate-bearing positively charged liposomes to rats.

The pharmacokinetics and tissue distribution of methotrexate (MTX) were investigated after intravenous (IV) and intramuscular (IM) injection of free MTX (treatment I), freshly prepared MTX-bearing positively charged liposomes (large unilamellar vesicles), PLUVs (treatment II), and empty PLUVs mixed manually with free MTX (treatment III), 4 mg kg-1 as free MTX to rats, using HPLC assay. After 1 min IV infusion, the plasma concentrations of MTX (Cp), the area under the plasma concentration-time curve (AUC, 173 against 314 micrograms mL min-1), the terminal half-life (t1/2, 24.0 against 412 min), the mean residence time (MRT, 13.0 against 324 min), and the apparent volume of distribution at steady state (VSS, 289 against 3370 mL kg-1) were significantly larger, but the total body clearance (CL, 23.1 against 12.8 mL min-1 kg-1), the renal clearance (CLR, 8.38 against 3.09 mL min-1 kg-1), the non-renal clearance (CLNR, 14.6 against 9.56 mL min-1 kg-1), and the amount of MTX excreted in urine (Xu, 415 against 275 micrograms) were significantly lower in treatment II than in treatment I. This could be due to the fact that some of the MTX-bearing PLUVs were entrapped in tissues and the rest were present in plasma (larger MRT and Vss in treatment II), and MTX is slowly released from MTX-bearing PLUVs (longer t1/2 in treatment II). In the present HPLC assay, the concentrations of MTX represent the sum of free MTX and MTX in MTX-bearing PLUVs (larger Cp and AUC and slower CL in treatment II). Saturable formation of 7-hydroxymethotrexate from MTX was reported in rabbit blood and nonlinear disposition of MTX was also reported in rats and rabbits (lower Xu and CLR in treatment II). After 1 min IV infusion, some pharmacokinetic parameters of MTX, such as AUC, CL, CLR, CLNR, and Xu, were significantly different between treatments I and III, but nonetheless the differences were smaller than those between treatments I and II. After both IV and IM administration, the amount of MTX remaining per gram of tissue or organ in the kidney, stomach, small intestine, and large intestine was significantly smaller in treatment II than in treatment I.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Indium-111 leukocyte accumulation in intramuscular injection sites.

We report four cases of indium-111 leukocyte concentration in previous intramuscular injection sites. Three patterns were observed: small, discrete, and round; linear; irregular and large. The scintigraphic appearance did not necessarily correlate with the number of injections that the patient had received.

Adult↗
PubMed2004

DNA immunization of mice with a plasmid encoding Neisseria gonorrhea PorB protein by intramuscular injection and epidermal particle bombardment.

Immunogenicity of a DNA vaccine encoding PorB from Neisseria gonorrhoeae strain FA1090 was analyzed in BALB/C mice immunized by intramuscular needle injection or epidermal gene gun bombardment. Both delivery routes generated measurable specific antibodies although the gene gun response was slower. Antibody isotypes were indicative of Th2 activation following gene gun immunization and of Th1 activation following intramuscular injection. In both immunization protocols, boosting with either renatured recombinant (rr) PorB protein or PorB expressed from Venezuelan equine encephalitis virus replicon particles (VRPs) significantly increased anti-PorB antibody levels. Boosting with rrPorB protein had little effect on antibody isotypes, while boosting with VRPs expressing PorB-enhanced a Th1 type response. Whole cell binding experiments showed that a portion of the antibodies recognized the surface of the homologous N. gonorrhoeae strain. Serum from groups with high antibody levels showed some opsonization of the homologous strain using human neutrophils. These results showed the potential of DNA vaccination for the purpose of priming an antibody response against PorB of N. gonorrhoeae. When combined with a protein or VRP boost, DNA priming resulted in high-titer and long-lasting responses. Based on different prime-boost protocols, we could polarize immune responses to predominantly Th1 or Th2, which should enable future studies of the types of immune responses that are protective in mouse models of gonorrhea.

Adjuvants, Immunologic↗
PubMed1991

Plasma estriol levels after intramuscular injection of estriol and two of its esters.

Twelve female volunteers from Berlin and 9 from Stockholm, all using a contraceptive pill (30 micrograms ethinyl estradiol and 150 micrograms levonorgestrel), received an intramuscular injection of estriol (E3; 1 mg in oil) on day 5 of withdrawal bleeding. Blood samples were collected at increasing time intervals during 4 weeks. Three months later, on day 5 of their withdrawal bleeding, 6 women were given intramuscularly (in oil) estriol 3,17-dipropionate (E3-prop) and 15 women estriol 3,17-dihexanoate (E3-hex). The doses were equivalent to 5 mg of estriol, i.e. 6.94 and 8.90 mg, respectively. Blood samples were collected during a period of 9 weeks. Estriol was analyzed by radioimmunoassay in all plasma samples. The average half-life of E3 ranged from 1.5 to 5.3 h after the administration of E3. It was 12.7 h and between 187 and 221 h after the administration of E3-prop and E3-hex, respectively. The average areas under the curve (in nmol.l-1.h) of E3 were between 82.5 and 161 after the administration of E3-prop or E3-hex, and between 27.1 and 37.9 when E3 had been given. As E3 was administered in a 5-fold lower dose than the esters, the areas under curve appeared to be comparable. Thus, the total exposure to E3 seemed to be almost independent of the type of E3 derivatization, while the time and intensity of exposure were very different.

Adult↗
PubMed1999

Experimental human muscle pain induced by intramuscular injections of bradykinin, serotonin, and substance P.

After intramuscular (m. tibialis anterior) injection of three different algogenic substances, the pain intensity was continuously scored on a visual analogue scale (VAS) in eight volunteers. The subject drew the distribution of the local and referred pain areas on a map. Four times within the first hour after injection, the pressure pain-thresholds (PPTs) and supra pressure-pain thresholds were assessed at the injection point, 2 cm distal from the injection site, at the arm, and at the contralateral leg. Measurements were done before and after injection of 0.5 ml of the algogenic substance [bradykinin (BKN), serotonin (5-HT), substance P (SP)], and isotonic saline as control. Cutaneous sensitivity to mechanical stimuli was assessed with a Von Frey hair at the same location as PPT determinations.The pain intensity (VAS-peak) after BKN (2, 4, and 10 nmol) and 5-HT (2, 4, and 20 nmol) was significantly higher (p< 0.05) than after SP (0.2, 0.4, and 0.8 nmol) and isotonic saline. The VAS-peak after infusions of hypertonic saline was significantly higher (p< 0.05) compared with VAS-peaks after all other substances. A significantly larger (p< 0.05) local pain area was found after BKN compared with isotonic saline. After injections of hypertonic saline, the offsets of evoked pain were significantly longer (p< 0.05) and the local and referred pain areas were significantly larger (p< 0.05) compared with all other substances. There was no dose-response relation between the pain intensity and the different doses of BKN, 5-HT, and SP. PPTs and skin sensitivity were not affected by any of the injections.We conclude that under the present experimental conditions, BKN and 5-HT can produce low levels of muscle pain after intramuscular injection. In the used concentrations, however, BKN, 5-HT, and SP did not generate cutaneous or muscular hyperalgesia. Copyright 1999 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗
PubMed2002

Allergic contact dermatitis from mercury antiseptics and derivatives: study protocol of tolerance to intramuscular injections of thimerosal.

BACKGROUND: Mercury derivatives are frequent contact allergens and their cross-reactivity is not constant. Thimerosal is an organic mercurial used as an antiseptic and as a preservative in most vaccines. OBJECTIVE: To evaluate cross-reactivity, exposure factors, and tolerance to vaccines containing thimerosal in patients sensitized to mercury derivatives. METHODS DESIGN: Observational study (cross-sectional); PATIENTS: 125 patients were recruited for the study, 72 women and girls and 53 boys and men, average age 18.7 years old, range 3 to 65, with positive patch tests to mercury derivatives and/or thimerosal; INTERVENTIONS: All patients were studied by means of enquiry, patch tests, intradermal tests, and intramuscular challenge with thimerosal. RESULTS: A sensitization to thimerosal was observed in 57 patients. Twenty-four of these 125 patients presented a positive intradermal reaction. Ammoniated mercury seems to be a good marker of mercury sensitization eliciting positive reaction in 78% of all patients and merbromin in 66%. In most cases, (100/125) cross-reactivity was found among mercury derivatives. The intramuscular injection of thimerosal induced a mild local reaction in only 5 patients (4% of the total, 9% of thimerosal positive reactions). Childhood vaccinations, merbromin used as an antiseptic, broken thermometers, and the use of drops were the main sources of exposure. CONCLUSIONS: The majority of the patients showed positive tests to both organic and inorganic mercury derivatives. Vaccination with thimerosal is relatively safe, even for individuals with delayed type hypersensitivity to this chemical, since more than 90% of allergic patients tolerated intramuscular challenge tests with thimerosal. A simplified protocol of patch tests to study mercury derivatives is proposed. It would be advisable to restrict the use of mercurial antiseptics and mercury thermometers.

Adolescent↗
PubMed1987

The effects of a single intramuscular injection of atropine sulphate on visual performance in man.

The effects of a single intramuscular injection of 2 mg atropine sulphate on visual function were studied in volunteer subjects. The well-known effects of increased heart rate, dryness of the mouth, increased pupil diameter and reduced accommodative range were confirmed. Visual acuity, stereoacuity, red-green colour balance and reaction time to a visual stimulus were unaffected by atropine, while extraocular muscle balance (horizontal heterophoria and cyclophoria) underwent a transient change. There was no significant change in contrast sensitivity measurements to stationary sinusoidal grating patterns of spatial frequencies 1-30 c/deg; however contrast sensitivity to moving grating patterns of spatial frequencies 1-5 c/deg showed a sustained reduction which was still present at 6 h post-injection. It is concluded that atropine adversely affects movement detection but not stationary visual function.

Atropine↗