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PubMed2005

Gene therapy for diabetes mellitus in rats by intramuscular injection of lentivirus containing insulin gene.

We assessed therapeutic potential of intramuscular insulin gene delivery in a diabetic murine model. The human proinsulin gene cDNA engineered with concensus furin cleavage sequences was inserted into an advanced lentiviral vector that contained CMV early promoter. After injection of concentrated lentiviral vector (3.5 microg p24 Gag antigen) carrying the insulin gene into the thigh muscle, treated rats demonstrated an increase in body weight, increased survivability, attenuated the hyperglycemic response as well as prevented the formation of ketoacidosis. For these reasons, the intraparenchymal injection of lentiviral vectors into the skeletal muscle to ectopically produce insulin may be an easy and therapeutic treatment modality for type 1 diabetes mellitus.

Animals↗
PubMed1994

Role of quinine in the high mortality of intramuscular injection tetanus.

There has been considerable uncertainty about the risks and severity of tetanus after intramuscular quinine, a widely used treatment of severe malaria in the rural tropics. We have compared the clinical features and outcome of tetanus in which injection was the only apparent site of infection with tetanus acquired by other routes in patients admitted to the Centre for Tropical Diseases, Ho Chi Minh City, Vietnam. In 1081 consecutive patients with tetanus treated between Jan 26, 1989, and May 27, 1991, 27 followed intramuscular quinine and 15 followed injections of other drugs. Overall mortality was 26% (285/1081). Mortality in patients who had not had preceding injections was 24% (250/1039) compared with 96% (26/27) in the quinine group (relative risk 4.0, 95% CI 3.5-4.6) (p < 0.0001), and 60% (9/15) in the other injections group (2.5, 1.6-3.8) (p < 0.005). 21 patients (78%) in the quinine group died within 72 h of admission compared with 5 (33%) in the other intramuscular injections group (p < 0.01) and 4 (7%) of 54 matched controls (p < 0.0001). Tetanus that follows intramuscular injections has a poor prognosis, but when it follows intramuscular quinine it is usually rapidly fatal.

Adult↗
PubMed1990

Pharmacokinetics of sulbactam/ampicillin in humans after intravenous and intramuscular injection.

We investigated the pharmacokinetic properties of sulbactam/ampicillin (S/A), after intravenous (0.5/1.0 and 1.0/2.0 g) and intramuscular (0.5/1.0 g) coadministration in 10 male subjects. After 1.0/2.0 g intravenous doses of S/A the half-lives (t1/2 beta) were 1.14 +/- 0.14/1.09 +/- 0.16 h. The values for plasma clearance (CLp) were 198.83 +/- 26.27/250.33 +/- 39.28 ml/min and the renal clearance (Clr) 173.50 +/- 19.66/208.80 +/- 26.43 ml/min. The post distributive volumes (V beta) were 19.67 +/- 3.24/23.56 +/- 5.76 liters. Similar values were obtained after 0.5/1.0 g of S/A intravenous coinjection. After 0.5/1.0 g intramuscular coadministration the t1/2 beta values were 1.26 +/- 0.18/1.20 +/- 0.15 h. The values for Clp were 208.00 +/- 28.73/243.17 +/- 33.24 ml/min, for Clr 179.50 +/- 20.26/202.67 +/- 27.61 ml/min and for V beta 22.27 +/- 4.12/25.30 +/- 4.87 liters. The renal clearance of sulbactam is comparable to that of ampicillin and both clearances are greater than the glomerular filtration rate, suggesting active renal tubular secretion of the two drugs. The large volumes of distribution, and the ratio K12/K21 = 0.5 show the extensive distribution of the two drugs into extracellular fluids. The very similar values of the pharmacokinetic parameters of sulbactam and ampicillin confirm that the kinetics of the two drugs closely resemble one another.

Adult↗
PubMed2005

Disposition kinetics of difloxacin in rabbit after intravenous and intramuscular injection of Dicural.

This study investigated the pharmacokinetic behaviour of difloxacin following a single intravenous (i.v.) bolus and intramuscular (i.m.) administration of 5 mg/kg body weight (bw) to rabbits (n = 6). Plasma concentrations were determined in triplicate by agar plate diffusion using E. coli (ATCC 25922) as the test organism. Difloxacin was assayed in plasma to determine its concentrations, kinetic behaviour and systemic availability. Plasma concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Difloxacin was rapidly distributed to the tissues with a steady-state volume of distribution (Vdss) of 1.51 L/kg and the total body clearance (Cltot) was 0.59 L/kg/h. The elimination half-lives after i.v. and i.m. administration were 3.25 h and 3.82 h, respectively. After i.m. administration, difloxacin was rapidly absorbed, with mean peak plasma concentration (Cmax of 3.85 microg/ml achieved at 1.61 h (Tmax) post administration. The extent of plasma protein binding of difloxacin in rabbits was 21.45% and the systemic bioavailability was 95.29%.

Animals↗
PubMed1976

Hemodynamic changes in rats after radioprotective combination of cystamine administered subcutaneously and 5-methoxytryptamine injected intramuscularly.

Administration of cystamine (20 mg base/kg s.c.) and 5-methoxytryptamine (10 mg base/kg i.m.) with 12 minutes delay to anesthetized rats induced the depression of whole cardiovascular system, hemoconcentration and great blood flow decrease in the radiosensitive tissues. Distributionof lowered cardiac output preferred the fractions to brain, heart, liver and lungs. Hemodynamic responses to protective combination may participate in its radioprotective action.

5-Methoxytryptamine↗
PubMed1985

Apramycin: minimal inhibitory concentrations for avian Escherichia coli and serum levels after intramuscular injection in turkeys.

The minimal inhibitory concentrations (MIC) of apramycin, a unique aminocyclitol antibiotic, for 100 Escherichia coli isolates recovered from clinical cases of avian colibacillosis were determined using the agar dilution method. All isolates were inhibited at apramycin concentration of 8.0 micrograms/ml; 90 and 50% of the isolates were inhibited at 6.6 and 3.4 micrograms/ml, respectively. A commercial injectable product containing 200 mg apramycin/ml was administered intramuscularly (i.m.) to groups of 6- and 12-week-old turkeys at 10, 15 and 20 mg/kg. Apramycin was quickly absorbed from the i.m. injection site. Mean peak serum drug concentrations were reached 1 h after treatment and were 19.5, 27.5 and 36.0 micrograms/ml, respectively. The serum elimination half-life (t 1/2) of the drug ranged between 1.75 h for the 10 mg/kg dose and 2.5 h for the 20 mg/kg dose. Very low concentrations of the drug were found 24 h after treatment. Duration of serum apramycin concentrations in relation to the MIC, dose, and age of birds was determined.

Age Factors↗
PubMed1996

DNA vector constructs that prime hepatitis B surface antigen-specific cytotoxic T lymphocyte and antibody responses in mice after intramuscular injection.

We tested the efficiency of induction of immune responses to the small hepatitis B surface antigen (HBsAg) in mice by intramuscular DNA immunization using different vector constructs that allow high levels of HBsAg expression in mouse cells. The HBsAg-specific responses of class I-restricted cytotoxic T lymphocytes (CTL) and of B cells (serum antibody titers) were measured. Following the intramuscular inoculation of 'naked' DNA, five different vector constructs of 4-8 kb, that contained or did not contain an intron and/or the neo gene, in which HBsAg expression was driven by promoter sequences derived from the immediate early region of HCMV, the SV40 enhancer/promoter region, or a retroviral 3' LTR efficiently primed responses of class I-restricted CD8+ CTL precursors. In contrast, the constructs in which HBsAg expression was driven by HCMV-derived promoter sequences stimulated significantly higher levels of HBsAg-specific serum antibody titers after intramuscular DNA injection than the SV40 or MPSV vector constructs. Large (15 kb) episomal vector constructs did not stimulate CTL or antibody responses. The data demonstrate that: (i) intramuscular DNA immunization represents an efficient technique for priming CTL and antibody responses to HBsAg; (ii) many vectors can be constructed that express an immunogenic product after intramuscular inoculation of 'naked' DNA; (iii) the efficiency of the tested vector constructs to prime after DNA immunization, either a CTL response, or an antibody response, differs.

Animals↗
PubMedDate not supplied

A double-blind study comparing single dose of intramuscularly injected zomepirac to meperidine in the treatment of postoperative pain.

Eighty-eight patients with moderate or severe postoperative pain were entered into a double-blind, single-injection trial designed to assess the analgesic efficacy of intramuscular zomepirac 100 mg. Patients were randomly selected to receive zomepirac injection, meperidine 100 mg or meperidine 50 mg. By most criteria of analgesic efficacy, zomepirac was superior to meperidine 50 mg and as effective as meperidine 100 mg. In terms of peak analgesia (and of patients' global evaluations), both meperidine 100 mg and zomepirac were superior to meperidine 50 mg. Total analgesia provided by zomepirac was greater than that with meperidine 100 mg, which was greater than that with meperidine 50 mg. Significantly fewer patients needed remedication during the observation period, and mean time to remedication was significantly longer for the zomepirac group than for either meperidine group. No serious adverse effects were reported.

Adult↗
PubMed1996

Bioequivalence study in calves of three commercial penicillin/dihydrostreptomycin fixed combination products for intramuscular injection.

A bioequivalence study with three penicillin/dihydrostreptomycin fixed combination products for intramuscular administration was performed in dairy calves. In addition to plasma concentrations of penicillin and dihydrostreptomycin, creatine phosphokinase concentrations were determined during a period of 72 h after administration of the drug products. Considerable differences were observed in the pharmacokinetics of penicillin from the three products. Although the extent of absorption was similar for all products, one product showed a significantly slower release from the site of injection. Except for the AUC, the 90% confidence intervals for these parameters exceeded the acceptable range of 0.80-1.20. Therefore, these products are not bioequivalent with respect to the rate of absorption of penicillin. Concerning the pharmacokinetics of dihydrostreptomycin in calves, it could not be concluded that the products were bioequivalent, since the 90% confidence intervals of the ratios for Cmax, tmax and MRT exceeded the range of 0.80-1.20. From this study in calves, it was also found that the product with the slowest release of penicillin from the injection site caused the most severe tissue damage, based on plasma creatine phosphokinase concentrations. Comparing the results from this study in calves with those from a previous study in rabbits, it can be concluded that the rabbit is a good animal model that could substitute for large animals, at least calves, in bioequivalence studies for penicillin/dihydrostreptomycin fixed combination products.

Analysis of Variance↗
PubMed1994

Induction of estrus with intramuscular injections of GnRH or PMSG in lactating goats (Capra hircus ) primed with a progestagen during seasonal anestrus.

In Experiment 1, goats in seasonal anestrus (n=154) were treated with sponges impregnated with 1 of 2 types of progestagen (MAP or FGA) followed by PMSG (400 IU im) 48 h before sponge removal. The type of progestagen used had no effect on kidding, abortion, pseudogestation, multiple births, stillbirths, number of live births per doe or gestation length. In Experiment 2, lactating goats (n=24) in seasonal anestrus were treated with progestagen sponges (MAP). At sponge removal they received one of the following treatments: 1 injection of PMSG (400 IU im), 1 injection of GnRH (125 mug im; GnRH-1), or 2 injections of GnRH (125 mug/injection im; GnRH-2) at a 48 h interval. Serum samples were taken at 6-h intervals for 96 h, starting 12 h after sponge removal. Heterologous radioimmunoassays were validated for the measurements of goat FSH, LH, E(2) and P(4). The onset of estrus (P=0.004), mean doe receptivity (P=0.0006), maximum preovulatory E(2) concentrations (P=0.0001) and LH peak concentrations (P=0.08) occurred significantly later for GnRH-1 and GnRH-2 than for PMSG treatment. The PMSG treatment induced a preovulatory LH peak in a greater number of goats (P=0.05) and gave a higher gestation rate than GnRH-1 and GnRH-2 treatments (57 vs 0 vs 12%; P=0.03). It is likely that the GnRH treatments administered did not reactivate the hypothalamo-pituitary-gonadal axis. Thus, intramuscular injections of GnRH in lactating goats primed with a progestagen were not as effective in regulating reproductive performance during seasonal anestrus as were injections of PMSG.

Journal Article↗
PubMed1999

Cloning of porcine prepro-orexin cDNA and effects of an intramuscular injection of synthetic porcine orexin-B on feed intake in young pigs.

Early growth is an important determinant of gain and efficiency in growing pigs. A major limiting factor of piglet growth is feed intake. Orexins, newly discovered neuropeptides, may be important regulators of appetite. The orexin gene, which encodes orexin-A and -B, was recently identified in rodents and man. The objectives of this study were to clone the cDNA for porcine orexin, utilize the cDNA sequence information to produce synthetic hormone, and evaluate the effect of orexin administration on feed intake in weanling pigs. Oligonucleotide primers were designed for reverse transcription polymerase chain reaction production of porcine orexin cDNA. The polymerase-chain-reaction products were cloned, sequenced, and found to be 88.5% homologous to the human orexin sequence. Predicted translation of porcine orexin cDNA revealed orexin-A and -B amino acid sequences that were 100% and 96% homologous to the known human peptides, respectively. Porcine orexin-B was synthesized according to the predicted sequence. Twenty-six cross-bred piglets were utilized in three replicates (n = 8-10/replicate). Piglets were weaned between 2-3 wk of age. One week after weaning, equal numbers of animals in each replicate received intramuscular (i.m.) injections of orexin-B (3 mg/kg body weight) or vehicle (sterile water). Feed intake was monitored from -24 to 24 h relative to injection (time 0). The orexin-injected pigs ingested an additional meal at 12 h when compared with the control animals (P = 0.02). Cumulative feed intake was increased by orexin-B administration from 12 to 24 h postinjection (P < or = 0.05). Total feed intake at 24 h was improved by 18% in orexin-treated pigs (P = 0.05). The ability to stimulate appetite during critical periods of early growth, particularly following weaning, could result in significant improvements in swine-production efficiency.

Amino Acid Sequence↗
PubMed2000

Treatment of severe hypercholesterolemia in apolipoprotein E-deficient mice by intramuscular injection of plasmid DNA.

We report on systemic delivery and long-term biological effects of apolipoprotein E (apoE) obtained by intramuscular (i.m.) plasmid DNA injection. ApoE plays an important role in lipoprotein catabolism and apoE knock-out mice develop severe hypercholesterolemia and diffuse atherosclerosis. We have injected apoE-deficient mice with 80 microg of a plasmid vector (pCMV-E3) encoding the human apoE3 cDNA under the control of the CMV promoter-enhancer in both posterior legs. Local expression of the transgene was demonstrated throughout 16 weeks. Human apoE3 recombinant protein reached 0.6 ng/ml serum level. After i.m. injection of pCMV-E3 expression vector the mean serum cholesterol concentrations decreased from 439 +/- 57 mg/dl to 253 +/- 99 mg/dl (P < 0.05) 2 weeks after injection and persisted at a significantly reduced level throughout the 16 weeks observation period (P < 0.005). Serum cholesterol was unaffected and reached an absolute level of 636 +/- 67 mg/dl in control groups. Finally, injection of pCMV-E3 into apoE-deficient mice resulted in a redistribution of cholesterol content between lipoprotein fractions, with a marked decrease in VLDL, IDL and LDL cholesterol content and an increase in HDL cholesterol. These results demonstrate that severe hypercholesterolemia in apoE-deficient mice can be effectively reversed by i.m. DNA injection, and indicate that this approach could represent a useful tool to correct several hyperlipidemic conditions resulting in atherosclerosis.

Analysis of Variance↗
PubMed2002

Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay.

The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian goats after intravenous and intramuscular administration of Baytril at the dose of 5mgkg(-1) bodyweight. A two compartment open model best represented the intravenous plasma concentration versus time data in both species. Comparisons between the means of the pharmacokinetic parameters obtained after intravenous administration of enrofloxacin (Baytril) revealed a significantly smaller distribution rate constant (lambda(1)) and consequently a shorter half-life time of distribution in sheep (P<0.05). A larger volume of the central compartment (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and goats for the remaining parameters. Plasma concentrations versus time data of enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and goats were adequately described by one-compartment open model with first order absorption and elimination. There were no significant differences between sheep and goats in any of the estimated pharmacokinetic parameters. The results indicate that the pharmacokinetics of enrofloxacin did not differ significantly between sheep and goats; similar intravenous and intramuscular dose rates of enrofloxacin should therefore be applicable to both species. Owing to the high variations in MIC (minimal inhibitory concentration) of sensitive veterinary pathogens, it is recommended that enrofloxacin dosage regimens be calculated according to the sensitivity of the individual pathogen, site of infection and clinical response, than by following a preset dosage regimen.

Animals↗
PubMedDate not supplied

Fever associated with repeated intramuscular injections of analgesics.

Five patients who developed a fever of undetermined origin during hospitalization are discussed. No infection was found in any of these patients. Occurrence of fever was temporally related to intramuscular (im) analgesic injections. In four cases damage of subcutaneous tissue was evident, and in two cases gallium scans showed uptake of gallium at injection sites. All five patients had received hydroxyzine either alone or in combination with other im analgesics. In addition, a retrospective chart survey of patients hospitalized for back pain who had received more than 30 im analgesic injections was carried out. Ten of 29 patients had fever lasting one to 15 days that could not be explained by the presence of obvious infection or inflammation or by the use of a nonanalgesic drug. In the chart survey it was found that febrile patients had been hospitalized significantly longer and had received more injections of all types and more injections of combinations of analgesics per patient than had afebrile patients. Thus, repeated im injections of analgesics may be associated with fever, with or without signs of tissue injury. Particular care should be taken in deciding whether im administration of hydroxyzine is necessary. Injection sites should be carefully monitored.

Analgesics↗
PubMed1975

[Poultry vaccination against N.C.D. by means of an intramuscular injection with LaSota strain vaccine; a practical investigation (author's transl)].

An intramuscular N.D.C. vaccination with LaSota vaccine, in animals of less than ten weeks which were previously vaccinated by the spray method at about 5 days and 25 days against N.C.D., leads to an immunity of at least three months, as expressed by a high concentration of haemagglutination inhibiting antibodies in the circulatory system. If the vaccinated animals are older than twenty weeks, the resulting immunity is very high indeed and shows practically no impairment within a year after vaccination (longer periods have not been investigated), so that it may be assumed that revaccination will not be necessary during the laying period. Antibody variations between different animals of a flock are slight. The residual immunity of previous vaccinations did not appear to affect the development or maintenance of the antibodies. No spread of vaccine was observed. Here it should be noted that animals with a low residual immunity were used for control. It would be desirable to use specifically pathogenfree animals for this purpose, but this is not really practicable in field conditions. Half a hen dose of the LaSota vaccine, dissolved in 1/2 ml physiological saline, was injected into the pectoralis muscle with the help of the Cornwall Pipetting Unit. Twenty flocks, involving 6900 animals, were vaccinated in field conditions. Not a single vaccination gave rise to any vaccination reaction. The method does have a high labour content; which is an objection.

Animals↗
PubMed2002

Serum pharmacokinetics and tissue and milk residues of oxytetracycline in goats following a single intramuscular injection of a long-acting preparation and milk residues following a single subcutaneous injection.

Separate groups of goats were used to determine drug depletion patterns in serum (n=10), tissue (n=20) and milk (n=8) following a single intramuscular (i.m.) dose of 20 mg/kg of a long-acting oxytetracycline (OTC) formulation (Liquamycin LA-200). Milk residues were also determined following a subcutaneous (s.c.) administration of the same product at the same dose. Serum samples were taken for 24 h post-treatment and tissues (fat, liver, kidney, muscle and injection site) collected at 4, 7, 14, 21 and 28 days following injection. Milk from lactating goats was collected every 12 h for 8 days following both the i.m. and s.c. treatments utilizing an intervening 5-week washout period. Residues in serum and tissue were measured using a microbial inhibition assay, while milk residues were measured using both a microbial inhibition assay and a validated HPLC method. The serum pharmacokinetic parameters of OTC in goats were determined, with a mean AUC=67.4 microg h/mL, mean terminal half-life=14.4 h, and apparent clearance=0.33 L/kg h. Tissue half-lives could not be determined with confidence because the collection times provided only two points at which residues could be measured for most tissues. Oxytetracycline residues in all goat tissue samples measured less then cattle tissue tolerance by 96 h postdosing. One-compartment model describing milk depletion data for i.m. and s.c. dosing had terminal slope half-lives of 20.1 and 36.1 h, respectively. By 96 h post-treatment none of the milk samples contained OTC residues in excess of the cattle milk tolerance (0.3 p.p.m.). For both milk and tissue, the upper-bound 99% confidence intervals for the samples taken from goats 96 h postdosing were lower than approved cow milk and tissue tolerances.

Animals↗
PubMed1995

Vaccine-associated paralytic poliomyelitis in the United States: no evidence of elevated risk after simultaneous intramuscular injections of vaccine.

During the past 30 years, Romania reported rates of vaccine-associated paralytic poliomyelitis (VAPP) approximately 10-fold higher than in the United States. The elevated VAPP risk was largely caused by multiple intramuscular (im) injections with antibiotics given within 30 days of onset of paralysis. Because it is not known whether im injections contribute to the VAPP risk in the United States, we examined VAPP cases reported since 1980. We reviewed injection histories of VAPP cases reported to the Centers for Disease Control and Prevention from 1980 to 1993: with vaccines for 1980 to 1987; and for all substances for 1988 to 1993. Rates of VAPP by number of im injections with vaccines were calculated from 1988 to 1993 with estimated vaccine coverage data from the National Health Interview Survey. From 1980 to 1993 a total of 119 cases of poliomyelitis were reported to the Centers for Disease Control and Prevention. Of these, 87 (73%) were vaccine-associated and immunologically normal: 41 were oral polio vaccine (OPV) recipient cases; 40 were OPV contact cases; and 6 were community-acquired cases. A history of im injections in the 45 days before onset of paralysis was obtained from 28 (72%) of 39 recipient cases reported from 1980 to 1993 for which dates of paralysis onset could be determined and from 1 (8%) of 13 contact cases reported from 1988 to 1993. With one exception all substances administered intramuscularly were routine childhood vaccines. No clustering of im injections in the "high risk" windows, 0 to 3 and 8 to 21 days before onset of paralysis, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗