RESUMEN
OBJECTIVE: To address the physiologic mechanism of isoflurane-associated reduction in hematologic variables in ferrets. ANIMALS: 6 young adult female ferrets. PROCEDURE: Distribution of 99mTc-labeled autologous erythrocytes was measured by serial in vivo imaging. Data were recorded in 4 ferrets, using a gamma camera, immediately prior to anesthesia, 15 minutes after 2% isoflurane anesthesia in O2 via endotracheal tube, 1 minute prior to and throughout a 10-minute phenylephrine infusion, 20 and 40 minutes after termination of the phenylephrine infusion, and 45 minutes after termination of anesthesia. Blood indices were also measured at times that paralleled those for imaging. One ferret served as a conscious control (no anesthetic administration), and another as an isoflurane control (no phenylephrine administration). RESULTS: In ferrets under anesthesia, splenic radioactivity increased from baseline of 10.2 +/- 2.0% to 38.4 +/- 3.2% (mean +/- SEM; P < 0.05) of the injected dose. Splenic radioactivity decreased to 13.4 +/- 3.8% of the injected dose during phenylephrine infusion and to near baseline for the recovery image. Splenic radioactivity in the conscious control remained constant throughout the study, whereas that of the anesthetized control was persistently increased throughout administration of isoflurane. Percentage reduction of the 15-minute sample values, compared with baseline values for all hematologic indices, was: RBC count, 33% (P < 0.05); hemoglobin concentration, 34% (P < 0.05); hematocrit, 35% (P < 0.05); and plasma protein concentration, 20% (P < 0.05). All RBC variables returned to within 7 to 14% of baseline by 45 minutes after termination of anesthesia. CONCLUSION: Isoflurane anesthesia causes splenic sequestration of RBC in ferrets that is partially reversed by phenylephrine infusion or termination of anesthesia. Thus, investigators and clinicians should be cautious when interpreting hematologic findings in isoflurane-anesthetized ferrets, and accordingly, fluid treatment and transfusion should be planned.
Asunto(s)
Anestesia por Inhalación/veterinaria , Eritrocitos/metabolismo , Hurones , Isoflurano , Animales , Recuento de Eritrocitos/efectos de los fármacos , Recuento de Eritrocitos/veterinaria , Eritrocitos/efectos de los fármacos , Femenino , Hurones/sangre , Hematócrito/veterinaria , Isoflurano/farmacología , Recuento de Leucocitos/efectos de los fármacos , Recuento de Leucocitos/veterinaria , Hígado/efectos de los fármacos , Pertecnetato de Sodio Tc 99m , Bazo/efectos de los fármacosRESUMEN
2-[18F]Fluoro-2-deoxy-L-glucose was synthesized from its trifluoromethanesulfonyl precursor. The precursor was prepared by selective acetylation and triflation of L-mannose. L-Mannose was first treated with acetic anhydride in the presence of a catalytic amount of perchloric acid and then reacted with phosphorus tribromide followed by aqueous sodium acetate to produce pure 1,3,4,6-tetra-O-acetyl-a-L-mannopyranose in 32% yield. This compound was treated with trifluoromethanesulfonic anhydride and pyridine in methylene chloride to form 1,3,4,6-tetra-O-acetyl-O-tritrifluoromethanesulfonyl-a-L-mannopyra nose in 77% yield. Nucleophilic substitution of the triflate with 18F-in the presence of Kryptofix 2,2,2 followed by acid hydrolysis produced 2-[18F]fluoro-2-deoxy-L-glucose with a radiochemical yield of 20-30% (EOS) within 90 min. Biodistribution studies in rats and PET imaging in Rhesus monkeys demonstrated that this sugar analog distributes in the extracellular space of most organs but is excluded from the CNS.
Asunto(s)
Desoxiglucosa/análogos & derivados , Radioisótopos de Flúor/química , Radiofármacos/química , Animales , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Desoxiglucosa/síntesis química , Desoxiglucosa/farmacocinética , Fluorodesoxiglucosa F18 , Marcaje Isotópico/métodos , Macaca mulatta , Masculino , Radiofármacos/farmacocinética , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Tomografía Computarizada de EmisiónRESUMEN
UNLABELLED: Antisense oligodeoxynucleotides coupled to asialoglycoprotein carrier molecules were evaluated in terms of their ability to accumulate preferentially in the liver and thus potentially serve as an important method to regulate liver gene expression. METHODS: Native and asialo-human alpha-1 acid glycoproteins were derivatized with low molecular weight poly(L)lysine and complexed with an antisense DNA (67 mer) complementary to the 5' end of rat serum albumin mRNA. The asialoglycoprotein antisense complex (conjugate) was characterized with respect to size, stability, and anti-sense loading, and the biodistribution of the conjugate was determined for normal rats at 5 min and 1, 6, and 24 hr after intravenous injection. In vivo stability of the anti-sense asialoglycoprotein complex was also evaluated using double-labeled (32P-antisense and 3H-glycoprotein) preparations. RESULTS: The results of the conjugate characterization studies demonstrated that at least 30% of the anti-sense DNA dissociated from the carrier after 7 min under chromatographic conditions. When the conjugate was incubated with PBS, MEM or MEM plus 10% FBS for 1 hr at 37 degrees C, about 85% of the antisense DNA was dissociated from the carrier. The results of the biodistribution studies showed that the accumulation of the asialo-glycoprotein anti-sense complex in the liver was rapid and greatly exceeded the accumulation of the sialo-glycoprotein antisense analog or antisense alone. CONCLUSION: These findings have significant implications for the targeted delivery of therapeutic antisense molecules to the liver.
Asunto(s)
ADN sin Sentido/genética , Expresión Génica , Hígado/metabolismo , Animales , Asialoglicoproteínas , Proteínas Portadoras/metabolismo , ADN sin Sentido/administración & dosificación , Masculino , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas , Distribución TisularRESUMEN
Biodistribution and infection imaging properties of 111In-DTPA-IgG, 99mTc-hydrazino nicotinamide-IgG and 111In-WBC were compared in rabbits with E. coli infection. Groups of six rabbits were injected with 10 mCi of 99mTc-IgG plus 0.5 mCi of 111In-IgG or 1 mCi of 99mTc-IgG plus 0.05 mCi of 111In-WBC. At 4-5 and 18-20 hr, dual photon scintigrams were acquired. At both times, the distributions of 99mTc and 111In-IgG were nearly identical. The sites of infection were well visualized with all three radiopharmaceuticals. In the early images, the target-to-background ratios (T/B) for 111In and 99mTc-IgG determined by ROI analysis were 1.95 +/- 0.26 and 2.57 +/- 0.38 (p = NS). In the delayed images, the T/B ratios increased (p < 0.01) to 3.56 +/- 0.49 and 4.90 +/- 0.98. At both times, the T/B ratios for 111In-WBC were higher (p < 0.01); 4.17 +/- 0.78 at 4-5 hr and 8.52 +/- 1.52 at 18-20 hr. These results indicate that all three agents yield excellent images of infection sites. Although 111In-WBC had higher T/B ratios, the ease of preparation of the radiolabeled proteins makes them attractive alternatives for infection imaging.