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Persistent expression of human clotting factor IX from mouse liver after intravenous injection of adeno-associated virus vectors.

We previously found that gene transduction by adeno-associated virus (AAV) vectors in cell culture can be stimulated over 100-fold by treatment of the target cells with agents that affect DNA metabolism, such as irradiation or topoisomerase inhibitors. Here we show that previous gamma-irradiation increased the transduction rate in mouse liver by up to 900-fold, and the topoisomerase inhibitor etoposide increased transduction by about 20-fold. Similar rates of hepatic transduction were obtained by direct injection of the liver or by systemic delivery via tail vein injection. Hepatocytes were much more efficiently transduced than other cells after systemic delivery, and up to 3% of all hepatocytes could be transduced after one vector injection. The presence of wild-type AAV, which contaminates many AAV vector preparations, was required to observe a full response to gamma-irradiation. Injection of mice with AAV vectors encoding human clotting factor IX after gamma-irradiation resulted in synthesis of low levels of human clotting factor IX for the 5-month period of observation. These studies show the potential of targeted gene transduction of the liver by AAV vectors for treatment of various hematological or metabolic diseases.

Animals↗

Renal CT after intravenous injection of nonionic dimeric or nonionic monomeric contrast media in healthy volunteers.

PURPOSE: To establish and compare time-density curves of the aorta, vena cava and renal cortex, medulla and pelvis after injection of the nonionic dimer iodixanol or the nonionic monomer iopromide contrast media. MATERIAL AND METHODS: In 36 healthy volunteers CT at the renal hilus was performed at regular intervals before and until 30 min after injection of 13.5 g I iodixanol or 15.0 g I iopromide. The density of the renal cortex, medulla, pelvis, aorta and inferior caval vein was measured. RESULTS: With injection of the 10% lower iodine dose in the iodixanol group, the profiles of the CT time-density curves were similar for all regions except for the renal pelvis. For the renal pelvis, significantly higher density values were obtained for the iodixanol group up to 10 min after injection. CONCLUSION: Although the present study shows that a lower iodine dose is needed for a dimeric compared to a monomeric nonionic contrast medium to obtain similar time-density curves, more studies are needed to establish the clinical importance of this for urography.

Adult↗

Comparison of manganese biodistribution and MR contrast enhancement in rats after intravenous injection of MnDPDP and MnCl2.

PURPOSE: To compare the time course of the MR enhancing properties and biodistribution of manganese (Mn) in rats given i.v. Mn dipyridoxyl diphosphate (MnDPDP) or Mn chloride (MnCl2). MATERIAL AND METHODS: Twenty-four adult rats were injected i.v. with 5 mumol/kg MnDPDP or MnCl2, or with 0.5 ml/kg saline. High resolution T1-weighted MR imaging was performed during early (10 min), mid (2 h) and late (24 h) phases after injection. Mn concentrations in major organs were measured by using an ICP-AES technique, and correlated with MR findings. RESULTS: Variable degrees of signal enhancement of major organs observed in MR images corresponded with the amount of Mn uptake after injection of MnDPDP or MnCl2. A prominently lower cardiac, pancreatic and hepatic uptake of Mn was seen at 10 min in rats injected with MnDPDP compared with those given MnCl2 and this was reflected in a difference in signal intensity (SI) in the MR images. At 2 h, the Mn content and SI in the major organs were similar with both MnDPDP and MnCl2. An overall Mn clearance was achieved at 24 h without any important organ retention, with kidney excretion of Mn seen only with MnDPDP. CONCLUSION: With both MnDPDP and MnCl2, the Mn uptake correlates with the SI enhancement in tissues. The reduced initial cardiac uptake of Mn after MnDPDP treatment compared to MnCl2 may account for the favourable cardiovascular safety of the contrast agent. These data contribute to an understanding of SI enhancement by MnDPDP, and are consistent with other studies showing that at a dose of 5 mumol/kg, MnDPDP can be safely used as a potent MR organ-specific contrast agent.

Animals↗

Pulmonary edema following intravenous injection of nonionic low-osmolar contrast medium--appearance on HRCT. A case report.

Pulmonary edema following i.v. contrast medium injection is a rare adverse reaction. We report on a 71-year-old woman who developed pulmonary edema following i.v. injection of iohexol during spiral CT of the thorax. She developed shortness of breath during the injection, and the first radiographic signs of pulmonary edema were visible on CT images 25 s after the onset of injection. On HRCT images 15 min later, marked edema was demonstrated in both lungs in a mosaic pattern of distribution. After appropriate therapy, the patient recovered without sequelae. A repeat CT 6 days later showed complete normalization.

Aged↗

Iodine concentrations in the rat kidney measured by X-ray microanalysis. Comparison of concentrations and viscosities in the proximal tubules and renal pelvis after intravenous injections of contrast media.

PURPOSE: To measure the iodine concentrations in the proximal tubules and renal pelvis after i.v. injections of contrast media (CM) at 1600 mg I/kg b.w., using a micropuncture technique and X-ray microanalysis. MATERIAL AND METHODS: The correlation between the viscosity of each CM and its iodine concentration was evaluated and the viscosity of the fluid in the proximal tubule and renal pelvis was estimated in rats. RESULTS: After iotrolan injection, the iodine concentration in the proximal tubular fluid had increased to values about three times higher than those reached with diatrizoate, iohexol and ioxaglate. Similarly, iotrolan tended to produce a higher iodine concentration in the renal pelvis than did the other CM. The urine viscosity in the renal pelvis was much higher after the iotrolan injection than after the other CM injections. CONCLUSION: High urine viscosity after iotrolan injection can at least partly explain our previous findings of a prolonged increase in tubular hydrostatic pressure and a prolonged decrease in the single nephron glomerular filtration rate after administration of this CM.

Animals↗

[Distribution of radioactivity in the body and rate of incorporation of radioactivity into the tissue proteins of monogastric animals following intravenous injection of tracer amino acids].

The studies were carried out with pigs and rats. The radioactive animo acids (14C leucine and 3H lysine) were administered to the pigs by way of a catheter tube into the jugular vein. Subsequently, the time pattern of the distribution of the specific amino acid radioactivity was followed in the TCE soluble and Tce precipitable fractions of the blood plasma (TCE= trichloro-acetic acid). The radioactive labelling in rats was carried out by injecting 14C leucine into the portal vein. The animals were killed after incorporation periods from 2 to 60 mins, and the levels of specific radioactivity were estimated in the TCE soluble and TCE precipitable fractions of the blood plasma, in the liver and in the skeletal muscles. The experimental results clearly indicated that the specific radioactivity of the tracer amino acids and the rate of incorporation of radioactivity into tissue proteins were greatly influenced by the size of the free amino acid pool within the range of distribution of the tracer. An estimation of the magnitude of the pool of free amino acids within the distribution range of the tracer can be obtained from the curve pattern for the decline of specific radioactivity of the corresponding free amino acid in the blood plasma. This pool exhibits a high rate of turnover. In all studies made to evaluate in vivo processes of protein synthesis by use of radioactive tracer amino acids it will be particularly important that consideration should be given to the specific radioactivity of the amino acid in the precursor pool for protein synthesis.

Amino Acids↗