Tail vein

A protease-specific model has also been reported in which a replication-defective adenovirus encoding an NS3 protease-SEAP fusion protein is injected into mouse tail veins, resulting in expression of the fusion protein in the liver [82, 83]. Protease activity can be detected both by measuring activity of liberated SEAP or by protease-induced liver damage. Protease activity was found to be reduced by administration of protease inhibitors. This model can be used to show that candidate inhibitors have adequate pharmacokinetic properties in mice to function in the intended target organ, but it is not a true disease model. 

Male Dublin-ICR white mice were administered pentylenetetrazol (dissolved in normal saline) by tail vein infusion. This slow intravenous infusion of PTZ to mice provided three consistent and easily measured endpoints for assessing anticonvulsant effects ... 

Diabetic Rats-Phase I. Laboratory rats (CD strain, 250-300g, male) were made diabetic by a single injection of streptozotocin (STZ), 50 mg/kg, into the tail vein. Nondiabetic controls received an equal volume of citrate buffer. Twenty-four hours after the STZ injection, each rat was individually housed for urine collection. The appearance of glucose in the urine (Ames test strips) and a predictable weight loss or depression of the growth curve were taken as confirming evidence of diabetes. 

Tumor cells. EMT6 cells were grown as a monolayer culture in DMEM medium containing 20% fetal calf serum (27). Cells were detached from the plate by trypsin-EDTA treatment and washed in PBS. A total of 5 x 103 cells were injected per mouse via the tail vein of Balb/c mice (6-8 weeks old) to induce experimental lung metastatic tumors. Immunoliposomes were injected iv 2 and 4 days after the tumor cell injection. The survival of mice was followed over the next 60 days. 

Figure 2. Lung uptake of GMj-containing or PS-containing liposomes. Liposomes (200/ig lipid) were injected via tail vein. Bar is S.D. (n=3). Data taken with permission from reference 14. Key , 34A-liposomes (PC chol GM.=10 5 1), Ab lipid= 1 11 (w/w), 297 nm in average diameter A, 34A-liposomes...

In toxicity studies, acute toxicity tests are usually carried out in the rat, mouse, cat, and dog. Subacute toxicity studies for IM products are performed by giving SC injections to rats and IM injections to dogs. In IV studies the rat tail vein or a front leg is used. Deliberate overdosing usually washes out metabolism differences between species. In dogs it is common to give an IV dose five times that intended for humans. In rats this is increased to 10 times. 

FIGURE 2 9-3 Intravenous administration of stem cells can reconstitute the blood forming system, and may provide cells to other tissues. In classical studies, Till and McCulloch administered dissociated bone marrow cells in the tail vein of lethally irradiated mice and found that the grafted cells repopulated the hematopoietic system and allowed the animals to survive. More recent studies suggest that blood cells also travel to sites of injury, where they may give rise to non-blood-tissue progeny. 

A series of thiazole-based DGAT-l inhibitors typified by the highly lipophilic compound 10 was disclosed [33]. This report described a tail-vein injection assay wherein a test compound (10, 30, and lOOmg/kg) and 20% emulsion containing a fatty acid mix were orally administered to male C57BL/6N mouse at 0.3ml/mouse. After 1 h following test compound administration, mice were anaesthetized and... 

The typical test (illustrated in Figure 15.7) is performed using mice, normally female CBA mice 6-10 weeks of age. Female BALB/c and ICR mice have also been used. After animal receipt, they are typically acclimated to standard laboratory husbandry conditions for 7-10 days. The usual protocol will consist of at least two groups (vehicle control and test article treated) of five mice each. They are treated on the dorsal surface of both ears with 25 pi (on each ear) of test article solution for three consecutive days. Twenty-four to forty-eight hours after the last test article exposure, the animals are given a bolus (0.25 ml) dose of [3H]thymidine (20 pCi with a specific activity of 5.0-7.0 Ci/mmol) in phosphate buffered saline via a tail vein. Five hours after the injection, the animals are euthanized by C02 asphyxiation and the auricular lymph nodes removed. 

Blood collection from the tail vein is a simple and rapid, nonsurgical method which does not require anesthesia. A relatively large number of serial samples can be obtained within a short period of time. However, this method is limited to relatively small sample volumes (<250 pi per sample). Although larger volumes can be obtained by placing the rat in a wanning chamber, this procedure could significantly influence the disposition of the test compound and therefore is not recommended for routine studies. Blood collected from the cut tail has been shown to provide valid concentration data for numerous compounds. 

The prophylactic antitumor efficiency was tested by injecting 12 mice twice in seven days with AVE 3 TRP-2 (10 pg TRP-2) and AVE 3 1826 CpG (1.3 pg CpG) intradermally the control group remained untreated. Seven days after the last immunization 2 x 10 B16 tumor cells in 200 pL HBSS were injected into the tail vein of each mouse. Twenty days after tumor inoculation, the animals were sacrificed and the metastases in the prepared lungs counted. As Table 2 shows, the liposomal vaccination has a significant effect on the tumor growth in comparison to untreated animals. This is also reflected by the visual appearance of the lungs (data not shown). 

In a typical procedure, a continuous wave laser (50 mW) excites ICG at 780 nm and the fluorescence signal is captured at 830 nm. Subsequent to a bolus injection in the tail vein of the rat, the time-dependent clearance of ICG from plasma can be monitored in real-time as shown in Eig. 9 for three rat data sets. 

Thee future prospects for naked DNA gene therapy include clinical trials for genetic diseases (e.g., Duchenne muscular dystrophy, ischemia, hemophilia), which would be initiated in the next few years, and tail vein injections in rodents, which will become a widely used technique for rapidly testing expression vectors/gene therapy approaches (101). 

Anesthetize animals (see Note 1), and take a blood sample from the jugular or tail vein into a capped 0.5- or 1.5-mL microcentrifuge tube to act as a preimmune sample. Allow it to clot, centrifuge at 1500g, remove the serum, and store at -20°C... 

Fig. 5.5. SERS image of mouse liver, a Whole-body map (1-mm steps) of nude mouse 2 h after tail vein injection of SERS nanoparticles. Most SERS particles accumulate in the liver (L, arrow), b Higher resolution (750 pm steps) and higher definition map of liver (arrow) showing organ detail including differentiation of the two liver lobes (reprinted with permission from [33]. Copyright 2008 National Academy of Sciences, USA)...

Zhang, G., Budker, V. and Wolff, J.A. (1999) High levels of foreign gene expression in hepatocytes after tail vein injections of naked plasmid DNA. Hum. Gene Ther., 10, 1735-1737. 

Figure 21.1 DNA dose-dependent gene expression. Various amounts of plasmid DNA (pCMV-Luc) were tail vein injected into mice (18-20 g). The level of luciferase gene expression in liver ( ), kidney (o), spleen ( ), lung ( ), and heart ( ) was measured eight hours post injection. Error bar represents S.E.M. from three animals. Reproduced with permission...

Figure 21.3 Histochemical analysis of / -galactosidase gene expression in liver. Ten pa of pCMV-LacZ plasmid DNA were injected into a mouse via the tail vein using the hydrodynamics-based procedure, / -galactosidase gene expression was assayed eight hours post injection. HV, hepatic vein HA, hepatic artery PV, portal vein (50x). (see Color Plate 15)...

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