Intramuscular injections in infants and children under 6 years of age.
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Two different studies are described. The first study deals with the elimination of residues of trimethoprim (TMP), sulfatroxazole (STX) and its main metabolite N4-acetyl-sulfatroxazole (N4-acetyl-STX) in pigs. Thirty -six pigs were treated with trimethoprim/sulfatroxazole IM in the nec k at a dosage of 16 mg/kg body weight for five days. Groups of four pig s were slaughtered at different time intervals. The study showed that concentration of STX, N4-acetyl-STX and TMP in edible tissues and at the injection sites were below 0.1 ppm on day nine after the last injection. S TX was eliminated the slowest, and STX can therefore be selected as a marker for residues of the trimethoprim/sulfatroxazole formulation in the tissues. The second study deals with irritation aspects of this trimethoprim /sulfatroxazole formulation. Four pigs of 32-35 kg were treated IM w with trimethoprim/sulfatroxazole and benzylpenicillin sodium. Each pig received the same injection volume, namely four trimethoprim/sulfatroxazole injections (16 mg/kg body weight per injection site), two in the back and two in the neck muscle, and two benzylpenicillin sodium injections (20,000 I.U./kg body weight per injection site), in the back muscle. All pigs were slaughtered 14 days after treatment and the extent of the irritation was compared. There were no differences between trimethoprim/sulfatroxazole and benzylpenicillin sodium with regard to irritation at the injection site in the back muscle. The irritation in the neck site was statistically less prominent than that in the back muscle and was considered not to affect the quality of the meat.
Expression of the firefly luciferase gene under the control of viral or fish promoters was observed in fish tissue after direct DNA injection of plasmid DNA. Plasmid DNA containing the firefly luciferase gene was injected into the skeletal muscle of rainbow trout (Oncorhynchus mykiss), and levels of luciferase activity were found to be dependent on the controlling promoter and the amount of injected DNA. Plasmids using the cytomegalovirus immediate early promoter (CMV-IEP) consistently produced the highest levels of luciferase activity. Maximal activity was observed five to seven days postinjection with 50 micrograms of DNA. This activity persisted in the tissues for as long as 115 days postinjection. When the DNA was examined up to two months postinjection, the predominant form was unreplicated, unintegrated DNA in linear and relaxed circular conformation. Expression of injected DNA was found predominantly within muscle cells along the injection path and in scattered muscle cells anterior to the injection site.
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Eleven juvenile Burmese pythons (Python molurus bivittatus) weighing 0.75-1.75 kg were randomly divided into two groups. Blood samples were obtained through surgically placed anterior carotid artery cannulas. Six pythons received a single i.m. injection of enrofloxacin at 5 mg/kg. Blood samples were obtained at 0.5, 1, 3, 6, 12, 24, 48, 72, and 96 hr postinjection. A mean (+/- SD) maximal plasma concentration of 1.66 (+/- 0.42) micrograms/ml was measured at 5.75 hr postinjection. The harmonic mean half-life was calculated to be 6.37 hr. The second group of five snakes received enrofloxacin at 5 mg/kg i.m. s.i.d. for 5 days. Blood was collected immediately before each injection and at 6 hr after each injection. Over the 5-day period, there was a stepwise increase in mean trough plasma concentrations of enrofloxacin. Clinically effective peak plasma enrofloxacin concentrations were attained after the first injection but did not significantly increase during the sampling period. Pharmacokinetic data were assessed against minimum inhibitory concentrations of enrofloxacin for Pseudomonas ssp. isolates in snakes obtained from historical data at the Veterinary Medical Teaching Hospital, University of Florida. Enrofloxacin should be administered at 10 mg/kg i.m. every 48 hr when treating Pseudomonas ssp. infections in juvenile Burmese pythons. Treatment of infections of more enrofloxacin-sensitive gram-negative bacteria could be achieved with the administration of an initial i.m. dose of 10 mg/kg followed by 5 mg/kg every 48 hr.
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BACKGROUND: Ischemic skeletal muscle has been shown to be advantageous for taking up and expressing genes transferred in the form of naked plasmid DNA. Therefore, acutely ischemic skeletal muscle may represent a potential target for IM gene therapy with naked DNA. Accordingly, we investigated the impact of IM injection of plasmid DNA encoding the secreted angiogenic growth factor, vascular endothelial growth factor (VEGF), on collateral vessel development in an animal model of acute hindlimb ischemia. METHODS AND RESULTS: After ligation of distal external iliac artery in New Zealand White rabbits, we directly injected 500 microg of phVEGF165 into the ischemic thigh muscles. At 30 days posttransfection, VEGF-transfected animals had more angiographically recognizable collateral vessels (angiographic score=0.72+/-0.06 versus 0.48+/-0.10; P<.01) as well as histologically assessed capillaries (248+/-37 versus 180+/-32/mm2, P<.01) compared to controls. Hemodynamic deficit was less severe in VEGF-transfected animals by calf systolic blood pressure ratio (0.80+/-0.09 versus 0.56+/-0.10, P<.01) and by flow to the ischemic limb measured with Doppler guidewire (resting flow=22+/-5 versus 14+/-4; P<.01; hyperemic flow=59+/-17 versus 39+/-12 mL/min; P<.05). Human VEGF mRNA was expressed in the transfected ischemic muscles as long as 14 days after gene transfer. Based on reporter plasmid expression, transfection efficiency was sixfold higher in ischemic muscles than in nonischemic control muscles. CONCLUSIONS: These results suggest the feasibility of employing direct IM transfer of naked VEGF plasmid DNA to optimize treatment of acute limb ischemia.
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The IFN-alpha cytokines belong to a multigene family. However, the in vivo biological functions of each of the IFN-alpha subtypes is unknown. Recently, we developed an experimental model in which the tibialis anterior muscles of mice were transfected in situ with naked DNA plasmids encoding an IFN transgene. Here we use this model to investigate the in vivo effect of the expression of three murine IFN-alpha subtypes (A1, A4, and A9) on murine CMV replication in C57BL/6, BALB/c, and A/J mice. CMV was shown to replicate in the tibialis anterior muscles of mice for at least 6 days and induced an inflammatory infiltrate. However, mice expressing the IFN-alpha transgenes showed a marked reduction in the peak titers of virus replication, with less severe inflammation in the muscles compared with control mice that were inoculated with blank vectors. Moreover, mice expressing the IFN-alpha1 transgene had significantly lower CMV titers in the inoculated muscle than mice expressing either the IFN-alpha4 or the IFN-alpha9 transgenes. Furthermore, IFN-alpha/beta receptor knockout mice had markedly higher levels of CMV replication in the tibialis anterior muscles than the wild-type parental strain (129/Sv/Ev) following IFN-alpha1 transgene inoculation, suggesting that the protection observed is due to host cell-mediated IFN signaling. These data provide the first evidence indicating that there are in vivo differences in the antiviral efficacy of the IFN-alpha subtypes.