In vivo application of [111In-DTPA-D-Phe1]-octreotide for detection of somatostatin receptor-positive tumors in rats.

Radioiodinated somatostatin analogues are useful ligands for the in vitro and in vivo detection of somatostatin receptors. [111In-DTPA-D-Phe1]-octreotide, a somatostatin analogue labeled with a different radionuclide, also binds specifically to somatostatin receptors in vitro. In this study we investigated its in vivo application in the visualization of somatostatin receptor-positive tumors in rats. The distribution of the radiopharmaceutical was investigated after intravenous injection in normal rats and in rats bearing the somatostatin receptor-positive rat pancreatic carcinoma CA 20948. After injection the radiopharmaceutical was rapidly cleared (50% decrease in maximal blood radioactivity in 4 min), predominantly by the kidneys. Excreted radioactivity was mainly in the form of the intact radiopharmaceutical. Ex vivo autoradiographic studies showed that specific accumulation of radioactivity occurred in somatostatin receptor-containing tissue (anterior pituitary gland). However, in contrast to the adrenals and pituitary, the tracer accumulation in the kidneys was not mediated by somatostatin receptors. Increasing radioactivity over the somatostatin receptor-positive tumors was measured rapidly after injection and the tumors were clearly visualized by gamma camera scintigraphy. In rats pretreated with 1 mg octreotide accumulation of [111In-DTPA-D-Phe1]-octreotide in the tumors was prevented. Because of its relatively long effective half-life, [111In-DTPA-D-Phe1]-octreotide is a radionuclide-coupled somatostatin analogue which can be used to visualize somatostatin receptor-bearing tumors efficiently after 24 hr, when interfering background radioactivity is minimized by renal clearance. This is an advantage over the previously used [123I-Tyr3]-octreotide which has a shorter effective half-life and shows high abdominal interference due to its hepato-biliary clearance. Therefore, [111In-DTPA-D-Phe1]-octreotide seems a better alternative for scintigraphic imaging of somatostatin receptor-bearing tumors.     

Specific localization of In-111-labeled monoclonal antibody versus 67-Ga-labeled immunoglobulin in mice bearing human breast carcinoma xenografts

Summary A murine monoclonal antibody reacting with more than 95% of all breast cancers was radiolabeled with In-111 and injected IP into nude mice bearing human breast carcinoma xenografts, together with Ga-67-labeled normal mouse immunoglobulin. Images were produced with a gamma camera in dual isotope mode. Tumors could be localized clearly with In-111-labeled specific monoclonal antibody, but improved visualization was obtained after computer-assisted subtraction of the image with Ga-67-labeled nonspecific immunoglobulin. The tumor-to-tissue contrast was improved from 2.3 to 5.9 after subtraction. Imaging with In-111-radiolabeled monoclonal antibody was superior to imaging with iodinated antibody. For the first time it was shown that images of two chemically related isotopes, Ga-67 and In-111, coupled to nonspecific and specific antibody, respectively, and simultaneously injected, can be subtracted to show the preferential uptake of the specific antibody in the tumor. As these isotopes are routinely used in clinical practice this technique may prove to be more practical for immunodetection of tumors in patients than existing imaging techniques.     

Pharmacological investigations on the adrenalin-thrombin-induced platelet aggregation in dogs

Adrenaline alone did not induce aggregation of canine blood platelets in citrated plasma in vitro; however, it potentiated the aggregation caused by thrombin concentrations which are too low to induce coagulation. Simultaneous infusion of adrenaline and thrombin resulted in accumulation of 111In-labelled platelets in the lung and in the heart as measured by means of a gamma camera. Separately infused adrenaline or thrombin did not change the distribution of radioactivity. In vitro and in vivo hirudin and cyproheptadine inhibited the adrenaline-thrombin-induced platelet aggregation. Dihydroergotamine exerted no in vivo effect at the doses used.     

Pulmonary edema and pleural effusion in norepinephrine-stimulated rats – hemodynamic or inflammatory effect?

Stimulation with norepinephrine (NE) leads to pulmonary edema and pleural effusion in rats. These pulmonary fluid shifts may result from pulmonary congestion due to the hemodynamic effects of NE and/or inflammation with an increase in vascular permeability. The contribution of these two factors were investigated in the present study. Female Sprague–Dawley rats received continuous i.v. NE infusion (0.1 mg/kg/h) over time intervals between 90 min and 72 h. After heart catheterization, pleural fluid (PF) and lung tissue were obtained. In some of the animals, a bronchoalveolar lavage (BAL) was performed. Pulmonary edema and inflammation were shown histologically. We determined the expression of interleukin (IL)-6 as one of the most potent acute-phase protein mediators in serum, PF and BAL supernatant fluid (BALF) using ELISA as well as in the lung tissue using Western blotting. Total protein concentration in BALF and PF served as indicators of increased capillary permeability. Pulmonary edema and pleural effusion appeared coincidentally with an increase in total peripheral resistance (TPR) after 6 h of NE infusion. PF reached a maximum between 8 and 16 h (2.2 ± 0.3 ml, controls < 0.5 ml) and disappeared within 48 h. Activation of IL-6 in the fluids was observed after 8 h of NE stimulation. In the lung tissue it started after 12 h and reached 330% of the control value after 48 h. Pulmonary inflammation was documented histologically. It was accompanied by increased protein concentration in BALF after 24 h of NE treatment. Hemodynamic effects of NE are the main causative factors in the initial phase of the pulmonary fluid shifts. Additionally, NE leads to an activation of cytokines such as IL-6 and to inflammation and to an increase in capillary permeability. However, inflammation and increased capillary permeability occurred later than pulmonary edema and pleural effusion. Hence, we conclude that they are secondary factors which may contribute to maintain the fluid shifts over a longer period of time.     

No gravity-independent gradient of blood flow distribution in dog lung

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.     

Longitudinal in vivo SPECT/CT imaging reveals morphological changes and cardiopulmonary apoptosis in a rodent model of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) has a complex pathogenesis involving both heart and lungs. Animal models can reflect aspects of the human pathology and provide insights into the development and underlying mechanisms of disease. Because of the variability of most animal models of PAH, serial in vivo measurements of cardiopulmonary function, morphology, and markers of pathology can enhance the value of such studies. Therefore, quantitative in vivo SPECT/CT imaging was performed to assess cardiac function, morphology and cardiac perfusion utilizing ²⁰¹Thallium (²⁰¹Tl) in control and monocrotaline-treated rats. In addition, lung and heart apoptosis was examined with ^99mTc-Annexin V (^99mTc-Annexin) in these cohorts. Following baseline imaging, rats were injected with saline or monocrotaline (50 mg/kg, i.p.) and imaged weekly for 6 weeks. To assess a therapeutic response in an established pulmonary hypertensive state, a cohort of rats received resveratrol in drinking water (3 mg/kg/day) on days 28–42 post-monocrotaline injection to monitor regression of cardiopulmonary apoptosis. PAH in monocrotaline-treated rats was verified by conventional hemodynamic techniques on day 42 (right ventricular systolic pressure (RSVP) = 66.2 mmHg in monocrotaline vs 28.8 mmHg in controls) and in terms of right ventricular hypertrophy (RV/LVS = 0.70 in monocrotaline vs 0.32 in controls). Resveratrol partially reversed both RVSP (41.4 mmHg) and RV/LVS (0.46), as well as lung edema and RV contractility +dP/dt_max. Serial ^99mTc-Annexin V imaging showed clear increases in pulmonary and cardiac apoptosis when compared to baseline, which regressed following resveratrol treatment. Monocrotaline induced modest changes in whole-heart perfusion as assessed by ²⁰¹TI imaging and cardiac morphological changes consistent with septal deviation and enlarged RV. This study demonstrates the utility of functional in vivo SPECT/CT imaging in rodent models of PAH and further confirms the efficacy of resveratrol in reversing established monocrotaline-induced PAH presumably by attenuation of cardiopulmonary apoptosis.     

Loss of surface coat by Strongyloides ratti infective larvae during skin penetration: evidence using larvae radiolabelled with 67gallium

The optimal conditions for labelling infective larvae of Strongyloides ratti with 67gallium citrate were determined. Radiolabelled larvae were injected s.c. into normal and previously infected rats. The distribution of radioactivity in these animals was compared with that in rats infected subcutaneously with a similar dose of free 67Ga by using a gamma camera linked to a computer system. Whereas free 67Ga was distributed throughout the body and excreted via the hepatobiliary system, the bulk of radioactivity in rats injected with radiolabelled larvae remained at the injection sites. Direct microscopical examination of these sites, however, revealed only minimal numbers of worms. When rats were infected percutaneously with radiolabelled larvae, it was found that most radioactivity remained at the surface, despite penetration of worms. When infective larvae were exposed to CO2 in vitro and examined carefully by light microscopy, loss of an outer coat was observed. It was concluded that infective larvae lose an outer coat on skin penetration.     

Regional trapping of microspheres in the lung compares well with regional blood flow

Microspheres (MS) are often used to measure the distribution of pulmonary blood flow in the assumption that the number of MS trapped in a region is proportional to blood flow. However, regional distribution of trapped MS has not been directly compared with regional blood flow in the lung. Regional trapping of MS was compared with regional flow of erythrocytes (RBC's) in isolated, perfused left lungs of dogs. Radioactivity from labeled MS and RBC's was measured by external detection using a gamma camera. We defined six regions of interest in the image of the left lateral surface of the lung: a dorsocaudal, a caudal, two ventral, an apical, and a central region. In each lung, regional trapping of MS was measured from the image of radioactivity obtained after slow injection of a suspension of MS into the arterial perfusion tubing. A radioactive bolus of labeled RBC's was injected during rapid imaging of the lung to obtain radioactivity vs. time curves from each region. The peaks of the regional radioactivity vs. time curves were used to estimate regional flows, though compensation had to be made for overlap of the washout and washin phases of the bolus of labeled RBC's. The results indicated that there were no differences in the regional distribution of MS compared with the regional distribution of RBC flow in isolated, perfused dog lungs.     

Alveolar fluid reabsorption is increased in rats with compensated heart failure

Alveolar fluid reabsorption (AFR) is important in keeping the air spaces free of edema. This process is accomplished via active transport of Na(+) across the alveolo-capillary barrier mostly by apical Na(+) channels and basolateral Na(+)-K(+)-ATPases. Recently, we have reported that acute elevation of left atrial pressures is associated with decreased AFR in isolated rat lungs. However, the effect of chronic elevation of pulmonary capillary pressure, such as seen in patients with congestive heart failure (CHF), on AFR is unknown. CHF was induced by creating an aorto-caval fistula (ACF) in Sprague-Dawley male rats. Seven days after the placement of the fistula, AFR was studied in the isolated perfused rat lung model. AFR in control rats was 0.49 +/- 0.02 ml/h (all values are means +/- SE) and increased by approximately 40% (0.69 +/- 0.03 ml/h) in rats with chronic CHF (P < 0.001). The albumin flux from the pulmonary circulation into the air spaces did not increase in the experimental groups, indicating that lung permeability for large solutes was not increased. Na(+)-K(+)-ATPase activity and protein abundance at the plasma membrane of distal alveolar epithelial tissue were significantly increased in CHF rats compared with controls. These changes were associated with increased plasma norepinephrine levels in CHF rats compared with controls. We provide evidence that in a rat model of chronic compensated CHF, AFR is increased, possibly due to increased endogenous norepinephrine upregulating active sodium transport and protecting against alveolar flooding.     

Effect of acute administration of mercuric chloride on the disposition of copper, zinc, and iron in the rat

The present study was designed to investigate the effect of mercuric chloride administration on copper, zinc, and iron concentrations in the liver, kidney, lung, heart, spleen, and muscle of rats. The results showed that after dose and time exposure to mercuric chloride, the concentration of mercury in the six tissues was significantly elevated. Data showed that there were no interaction between mercury and tissue iron. There was a considerable elevation of the content of copper in the kidney and liver. The most significant changes in the copper concentration took place in the kidneys. About a twofold increase in the copper content of the kidney was noted after exposure to mercuric chloride (3 mg and 5 mg/kg). Only slight elevations in the copper content occurred in the liver, especially in high dose and longer exposure time. In the remaining organs, the copper content was not changed significantly (p>0.05). The most significant changes in the zinc concentration took place in liver, kidney, lung, and heart (5 mg/kg). Marked changes in kidney zinc concentrations were observed at any of the specified doses. Zinc concentrations were significantly increased in kidney of rats sacrificed 9–48 h after sc injection of HgCl₂ (5 mg/kg); in liver obtained from rats at 18, 24, or 48 h after injection; and in lung after 24 or 48 h of treatment. The heart and spleen zinc concentrations were elevated at 24 and 48 h after injection of HgCl₂ (5 mg/kg), respectively. The results of this study implicate that effects on copper and zinc concentrations of the target tissues of mercury may play an important role in the pathogenesis of acute mercuric chloride intoxication.     

Interleukin-1 increases norepinephrine turnover in the spleen and lung in rats

To clarify effects of interleukin-1 on sympathetic nerve activity, norepinephrine turnover in various organs was assessed in rats after intraperitoneal injection of recombinant human interleukin-1 beta. Interleukin-1 administration increased norepinephrine turnover in the spleen, lung and hypothalamus without appreciable effect in the heart, liver, submandibular gland, thymus, pancreas, brown adipose tissue and medulla oblongata. Similar changes in norepinephrine turnover were also found after the administration of bacterial endotoxin. It was concluded that interleukin-1 activates the sympathetic nerves specifically in the spleen and lung.     

Evaluation of a maleimido derivative of NOTA for site-specific labeling of affibody molecules

Radionuclide molecular imaging has the potential to improve cancer treatment by selection of patients for targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. The NOTA chelator forms stable complexes with a number of radionuclides suitable for SPECT or PET imaging. A maleimidoethylmonoamide NOTA (MMA-NOTA) has been prepared for site-specific labeling of Affibody molecules having a unique C-terminal cysteine. Coupling of the MMA-NOTA to the anti-HER2 Affibody molecule Z(HER2:2395) resulted in a conjugate with an affinity (dissociation constant) to HER2 of 72 pM. Labeling of [MMA-NOTA-Cys(61)]-Z(HER2:2395) with (111)In gave a yield of >95% after 20 min at 60 °C. In vitro cell tests demonstrated specific binding of [(111)In-MMA-NOTA-Cys(61)]-Z(HER2:2395) to HER2-expressing cell lines. In mice bearing prostate cancer DU-145 xenografts, the tumor uptake of [(111)In-MMA-NOTA-Cys(61)]-Z(HER2:2395) was 8.2 ± 0.9% IA/g and the tumor-to-blood ratio was 31 ± 1 (4 h postinjection). DU-145 xenografts were clearly visualized by a gamma camera. Direct in vivo comparison of [(111)In-MMA-NOTA-Cys(61)]-Z(HER2:2395) and [(111)In-MMA-DOTA-Cys(61)]-Z(HER2:2395) demonstrated that both conjugates provided equal radioactivity uptake in tumors, but the tumor-to-organ ratios were better for [(111)In-MMA-NOTA-Cys(61)]-Z(HER2:2395) due to more efficient clearance from normal tissues. In conclusion, coupling of MMA-NOTA to a cysteine-containing Affibody molecule resulted in a site-specifically labeled conjugate, which retains high affinity, can be efficiently labeled, and allows for high-contrast imaging.     

Radiation injury in rat lung. I. Prostacyclin (PGI2) production, arterial perfusion, and ultrastructure

Pulmonary prostacyclin (PGI2) production, arterial perfusion, and ultrastructure were correlated in rats sacrificed from 1 day to 6 months after a single exposure of 25 Gy of gamma rays to the right hemithorax. PGI2 production by the irradiated lung decreased to approximately half the normal value 1 day after irradiation (P less than 0.05), then increased steadily throughout the study. By 6 months postirradiation, the right lung produced two to three times as much PGI2 as did either shielded left lung or sham-irradiated lungs (P less than 0.05). Perfusion scans revealed hyperemia of the right lung from 1 to 14 days after irradiation. From its peak at 14 days postirradiation, however, perfusion of the irradiated lung decreased steadily, then reached a plateau from 3 to 6 months at less than half that in the shielded left lung. Electron micrographs of the right lung revealed perivascular edema from 1 to 30 days after irradiation. The right lung then exhibited changes typical of radiation pneumonitis followed by progressive interstitial fibrosis. Platelet aggregates were not observed at any time. Thus, decreased PGI2 production is an immediate but transient response of the lung to radiation injury. Then from 2 to 6 months after irradiation, the fibrotic, hypoperfused lung produces increasing amounts of the potent vasodilator and antithrombotic agent, PGI2. Pulmonary PGI2 production and arterial perfusion are inversely correlated for at least 6 months after hemithoracic irradiation.     

Impaired in vivo myocardial reactivity to norepinephrine in diabetic rats

The effects of long-term diabetes with and without insulin treatment on in vivo myocardial contractile activity were studied under basal conditions and as a function of intravenously infused norepinephrine. Diabetes was induced by iv injection of streptozotocin (50 mg/kg). Insulin-treated diabetic rats received 5 units per day of isophane insulin suspension. The duration of the study was 8 weeks. In vivo myocardial contractility measurements were performed in ketamine-xylazine-anesthetized rats using a miniature catheter-tip pressure transducer advanced through the right carotid artery into the left ventricle. Peak positive dP/dt and intraventricular developed pressure were comparable among the groups when measured under basal conditions; however, the magnitude of the response to variable doses of norepinephrine (6 X 10(-12) to 6 X 10(-8) mole/kg body wt) were significantly diminished in diabetic rats, but the sensitivity was unchanged. Negative dP/dt was decreased under basal conditions and in response to norepinephrine in diabetic rats. Insulin treatment to diabetic rats prevented these changes, but heart rate was elevated. These results demonstrate that the in vivo cardiovascular reactivity of diabetic rats to norepinephrine is significantly attenuated.     

Tumor localization of Lewis lung carcinoma with radiolabeled monoclonal antibodies

Summary Mouse 6D6 IgG_2a and 5B5 IgM monoclonal antibodies which specifically bind murine lung carcinoma cells (3LL cells) were injected to healthy and tumor-bearing mice. In vivo localization was analyzed by counting the tissue radioactivity and by external gamma ray scintigraphy at various times after IV injection of ¹²⁵I- or ¹³¹I-labeled antibodies. The clearance of the two monoclonal antibodies was not modified by the presence of the tumor, and the 6D6 IgG_2a was cleared at a rate slower than the 5B5 IgM. Both antibodies gave a high specific uptake at the tumor level; the tumor-to-healthy tissue ratios were higher with the 6D6 IgG_2a than the 5B5 IgM; unspecific mouse immunoglobulins (IgG₂) did not localize in the tumor. The amount of 6D6 IgG_2a antibody still associated with the tumor after 2 days following IV injection was 10 times higher than that of 5B5 IgM, and was still high enough to localize the tumor after 5 days.Imaging experiments confirmed the ability of 6D6 IgG_2a to detect the presence of tumor cells. The targeting kinetics determined by computer analysis of camera images indicated a rapid targeting of antibodies in tumor with a maximal concentration after 4–6 h; after 48 h the background was quite low and the 6D6 IgG_2a appeared to be specifically localized in the tumor.     

Pulmonary neutrophil kinetics in sheep: effects of altered hemodynamics

We investigated the effect of elevated left atrial pressure and reduced cardiac output on pulmonary neutrophil kinetics in the sheep. Sheep neutrophils were isolated, labeled with 111In-oxine, and reinfused. Erythrocytes were labeled with [99mTc]pertechnetate. A gamma camera measured the lung activities of the labeled neutrophils and erythrocytes. The results indicated that 38.5% of the total injected neutrophils marginated in the lung. Pulmonary hemodynamics were altered by inflating a left atrial balloon three times in each sheep for 15-30 min to achieve 5- to 25-mmHg increments in pulmonary arterial wedge pressure. At least a 30-min recovery period was allowed between inflations. After each left atrial balloon inflation, neutrophil uptake remained unchanged from base line, despite decreased mean cardiac output to 0.67 +/- 0.24 (+/- SD) 1/min and increased pulmonary blood volume. The absence of pulmonary neutrophil uptake was confirmed by arterial-venous measurements. Increased pulmonary blood volume had little effect on lung neutrophil uptake, suggesting that most of the pulmonary neutrophils are marginated. We conclude that the lungs have a large marginated neutrophil pool compared with the circulating pool and that reduced cardiac output and elevated left atrial pressure have no effect on pulmonary neutrophil kinetics in the sheep.     

Systemic perfusion: a method of enhancing relative tumor uptake of radiolabeled monoclonal antibodies

We evaluated the feasibility of systemic vascular perfusion with saline (mimicking plasmapheresis) as a method to enhance tumor-specific monoclonal antibody (MoAb) tumor/background ratios. Initially, groups of rats were injected intravenously (i.v.) with ¹³¹I-5G6.4 MoAb (murine IgG2aK reactive with ovarian carcinoma). These animal's radioactivity levels were determined by dose calibrator and they were imaged before and after perfusion which was conducted at 4 or 24 h post-antibody injection. Animals were sacrificed after perfusion, as were controls, and normal organ radioactivity levels determined. In addition, nude mice bearing HTB77 ovarian cancers subcutaneously were injected i.v. with ¹³¹I-5G6.4 MoAb and were imaged before and after systemic perfusion with saline 24 h post-5G6.4 injection. Perfusion in rats dropped whole-body 5G6.4 levels significantly at both perfusion times (P < 0.0005). The drop in whole-body radioactivity with perfusion was significantly greater for the animals perfused at 4 h post i.v. 5G6.4 antibody injection (48.3 ± 5.1%) than for those perfused at 24 h post i.v. antibody injection (32.9 ± 2.9%) (P < 0.025). In the nude mice with ovarian cancer xenografts, γ camera images of tumors were visually and quantitatively (by computer image analysis) enhanced by perfusion, with a 2.33-fold greater decline in whole body uptake than in the tumor (P < 0.05). These studies show that (1) much background antibody radioactivity can be removed using whole-body perfusion with saline, (2) that the decline in whole body activity is larger with 4 than 24 h perfusion and (3) tumor imaging can be enhanced by this approach. This and similar approaches that increase relative tumor antibody uptake such as plasmapheresis may be useful in imaging and therapy with radiolabeled antibodies.     

海水淹溺致大鼠急性肺损伤模型的建立

目的：建立海水淹溺肺损伤（SWD-ALl）的大鼠模型,为SWD—ALl的基础及救治研究提供平台。方法：128只健康SD大鼠随机分为4组,即对照（CG）组和海水灌注（SGI、SG2、SG4）组（分别气管内注入1、2、4mL／kg海水）。观察大鼠气管内海水灌注后症状以及各组呼吸频率、心率、动脉血气、肺湿／干重r~（W／D）,留取肺组织病理标本观察病变。结果：与对照组比较,海水灌注组大鼠心率、呼吸频率明显加快,气道有白色泡沫渗出物,口唇发绀,肺部满布湿罗音。动脉血气分析氧分压（PaO2）和二氧化碳分压（Pa—CO2）显著降低（P〈0．01）;SGl、SG2组30min测氧合指数（Pa02／FiO2）低于300mmHg,之后逐渐升高至接近正常,SG4组各时间点测PaOJFi02得均在300mmHg以下;各组间比较,SG4组肺组织湿／干重比（W／D）明显高于其他组（P〈0．01）。肺组织病理观察,光镜下肺间质水肿,肺泡隔断裂,大量的红细胞及炎性细胞浸润。结论：经气管内灌注海水4mL／kg,可成功建立海水淹溺急性肺损伤的动物模型。     

Opiate and alpha receptor antagonists block the pressor responses of conscious rats given intravenous dynorphin

Conscious, unrestrained rats were used to determine the hemodynamic (blood pressure and heart rate) responses following intravenous (IV) injection of dynorphin A(1-13) and the possible receptor mechanisms mediating those changes. Male Sprague-Dawley rats (300 g) were given IV bolus injections (via femoral venous catheter) of 6.0 to 600 nmoles/kg of dynorphin A(1-13), 8.0 nmoles/kg of norepinephrine HCl (NE), 14.3 pmoles/kg of angiotensin II or a vehicle control solution. Blood pressure (BP) and heart rate (HR) were monitored via femoral arterial catheter (into abdominal aorta) over 90 sec postpeptide or -amine administration before and 10 min after IV injection of 4.2 mumoles/kg of naloxone HCl (opiate antagonist), yohimbine HCl (alpha 2 receptor antagonist) or prazosin HCl (alpha 1 receptor antagonist). Dynorphin A(1-13) caused a transient but dose-related rise in mean arterial pressure (MAP) whereas mean pulse pressures (MPP) and mean heart rates (MHR) concomitantly fell, from preinjection control values in a dose-dependent fashion. Pretreatment with naloxone blocked the pressor response of only a subsequent injection with 20 nmoles/kg but not 60 nmoles/kg of dynorphin A or NE (8.0 nmoles/kg). Pretreatment with yohimbine suppressed the marked pressor responses of subsequent NE or Dyn A (60 nmoles/kg) administration whereas prazosin antagonized the rise in MAP of only the lower doses of dynorphin as well as NE. The suppression of the pressor responses of dynorphin by opiate or alpha receptor antagonists were not caused by tachyphylaxis for repeated injections of 6.0 or 60 nmoles/kg of dynorphin caused the same rise in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)     

The advantages and limits of indium-111 labeling of antibodies experimental studies and clinical applications

Radiolabeling of antibodies with In-111 has now been accomplished to the point that it is highly reproducible, achieves excellent labeling efficiency, and does not damage the antibody. Use of In-111 for radioimmunodetection is advantageous because of the excellent imaging characteristics of the In-111, moderate radiation dose, ease of labeling, and appropriate half-life. The liabilities of the In-111 method include slightly greater cost of the radionuclide, slow clearance of background sites, and a shelf life requiring it to be ordered on a weekly basis.When all characteristics of the radionuclide are taken into account, it appears to be superior to I-131 for radioimmunoimaging. A controlled study using iodinated and Indium labeled antibodies in the same group of patients needs to be done to accurately access how well the two function for tumor detection.