phosphorus-radioisotopes and Disease-Models--Animal

Our laboratory has developed a novel delivery platform using an attenuated non-toxic and non-pathogenic bacterium Listeria monocytogenes that infects tumor cells and selectively survives and multiplies in metastases and primary tumors with help of myeloid-derived suppressor cells (MDSC) and immune suppression in the tumor microenvironment (TME). 32P was efficiently incorporated into the Listeria bacteria by starvation of the bacteria in saline, and then cultured in phosphorus-free medium complemented with 32P as a nutrient. Listeria-32P kills tumor cells through both 32P-induced ionizing radiation and Listeria-induced reactive oxygen species (ROS). The levels of 32P and Listeria were studied in various normal and tumor tissues, at sequential time points after injection of mice with pancreatic cancer (syngeneic model Panc-02). We found that 32P and Listeria predominantly accumulated in tumors and metastases, with their highest accumulation 4 hrs (32P) and 3 days (Listeria) after injection. Listeria also penetrated the transgenic KPC (conditionally express endogenous Kras-G12D and p53-R172H mutant alleles) pancreatic tumors and metastases. This is remarkable since KPC tumors, like human tumors, exhibit a stromal barrier, which prevents most drugs from penetrating the pancreatic tumors. Therapeutic treatment with Listeria -32P resulted in a strong reduction of the growth of pancreatic cancer at early and late stages in Panc-02 and KPC mice. These results highlight the power of Listeria as new delivery platform of anticancer agents to the TME. Not only were therapeutic levels of radioactive Listeria reached in tumors and metastases but the selective delivery also led to minimal side effects.

Topics: Animals; Antineoplastic Agents; Disease Models, Animal; Drug Delivery Systems; Listeria monocytogenes; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Pancreatic Neoplasms; Phosphorus Radioisotopes

The study aims to characterize age-associated changes in skeletal muscle bioenergetics by evaluating the response to ischemia-reperfusion in the skeletal muscle of the Goto-Kakizaki (GK) rats, a rat model of non-obese type 2 diabetes (T2D). (31)P magnetic resonance spectroscopy (MRS) and blood oxygen level-dependent (BOLD) MRI was performed on the hindlimb of young (12 weeks) and adult (20 weeks) GK and Wistar (control) rats. (31)P-MRS and BOLD-MRI data were acquired continuously during an ischemia and reperfusion protocol to quantify changes in phosphate metabolites and muscle oxygenation. The time constant of phosphocreatine recovery, an index of mitochondrial oxidative capacity, was not statistically different between GK rats (60.8 ± 13.9 sec in young group, 83.7 ± 13.0 sec in adult group) and their age-matched controls (62.4 ± 11.6 sec in young group, 77.5 ± 7.1 sec in adult group). During ischemia, baseline-normalized BOLD-MRI signal was significantly lower in GK rats than in their age-matched controls. These results suggest that insulin resistance leads to alterations in tissue metabolism without impaired mitochondrial oxidative capacity in GK rats.

Topics: Animals; Brain Ischemia; Diabetes Mellitus, Type 2; Disease Models, Animal; Hydrogen-Ion Concentration; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mitochondria; Muscle, Skeletal; Phosphocreatine; Phosphorus Radioisotopes; Rats; Reperfusion Injury

The purpose of this study was to investigate the therapy effects of intratumoral administration of (32)P-CP-PLLA particles in a rabbit VX2 lung tumor model.. 16 rabbits with tumors were randomly divided into 4 groups. 4 rabbits served as untreated controls, and others received intratumoral administration of (32)P-CP-PLLA particles with CT guidance. The total radioactivities in treated groups were as follows: a low activity was 93 MBq (n=4) (group 1), a medium activity was 185 MBq (n=4) (group 2) and a high activity was 370 MBq (n=4) (group 3). Brachytherapy treated VX2 tumors underwent (18)F-FDG PET/CT at 0 day, 3 day, 7 day and 14 day postinjection. In control group, (18)F-FDG PET/CT images were acquired at the same time points but without any treatment. Bremsstrahlung SPECT images were performed at 14 days after intratumoral brachytherapy in treated groups. After Bremsstrahlung SPECT and last (18)F-FDG PET/CT imagings, the rabbits were euthanized and the tumors were removed for histological examination.. Bremsstrahlung SPECT images study indicated that there was no leakage of (32)P out of the injection site at 14 days after treatment. Compared with the control, the tumor volumes in treated groups significantly decreased, and (32)P-CP-PLLA particle produced a reduction in maximum or mean SUV of VX2 tumor (p<0.05). The percentage changes in maximum and mean SUV gradually decreased in group 1 and group 2 from day 3 to day 14 (p<0.05). A transient increase in (18)F-FDG accumulation at group 3 occurred due to the inflammatory reaction elements. Activity dependence was seen in HE and PCNA staining after 14 days treatment among three treated groups (p<0.05).. Our data suggested that (32)P-CP-PLLA particle localized on the injecting sites. This novel brachytherapy device efficiently suppressed the growth of the VX2 tumors implanted in the rabbit.

Topics: Animals; Brachytherapy; Disease Models, Animal; Fluorodeoxyglucose F18; Lactic Acid; Lung Neoplasms; Phosphorus Radioisotopes; Polyesters; Polymers; Rabbits; Radiopharmaceuticals; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Tumor Burden

³²P-chromic phosphate-poly (L-lactic) acid (³²P-CP-PLLA) microparticle is a novel potent brachytherapy implant, which has good biocompatibility and biodegradability. The aim of this study is to investigate the changes of pathology and PET/CT images in VX2 rabbit tumor after treatment with intratumorol administration of ³²P-CP-PLLA microparticles, and to explore the effects and influence of tumor growth and apoptosis related proteins in VX2 lung tumor treatment with ³²P-CP-PLLA microparticles.. Twenty-four tumor bearing rabbits were randomly divided into 4 groups (6 in each group). Group 1, 2 and 3 were treated groups; group 4 was the control. Under CT guidance, ³²P-CPPLLA microparticles were implanted into tumors. Low, medium and high treatment doses were 93 MBq (group 1), 185 MBq (group 2) and 370 MBq (group 3), respectively. ¹⁸F-FDG PET/CT was performed at d0, d3, d7 and d14 after intratumoral administration. In the control group, ¹⁸F-FDG PET/CT images were acquired at the same time points but without treatment. The standardized uptake value (SUV) of tumor regions were calculated. After last PET/CT imaging, the rabbits were euthanized and the tumors were removed for histological and immunohistochemical examination. The pathology and the expression of apoptosis related proteins (bcl-2, bax) were compared.. No significant difference of SUVmax was observed between the treatment groups and the control group at d0. At d14, the SUVmax values for group 1, 2 and 3 were 0.80±0.10, 1.1±0.19 and 2.85±0.15, respectively, and were significantly lower than that of the control group (5.61±0.50)(P < 0.05). Significant dose-response relationship was observed in SUVmax between group 1 and group 2, and the SUV values gradually decreased from d7 to d14 after treatment. In group 3, SUVmax gradually increased and reached a peak at d7 then significantly decreased. The SUVmax values of group 3 were significantly lower than those of the control at the same time point (P < 0.05). HE staining found degenerative necrosis at the site was nearby the microparticle. Necrosis became serious increasing with the radioactivity. Inflammatory cell infiltration was rarely seen in tumors treated with 93 MBq or 185 MBq ³²P-CP-PLLA microparticles. In contrast, the necrotic area was surrounded by marked inflammatory cell infiltration in group 3. IHC analysis showed that the expression of bcl-2 in treated groups were lower than those in the control group, and the expression of bax in treated group was higher than those in the control group (P < 0.05). The ratio of bcl-2/bax protein significantly decreased in the treated group (P < 0.05). Dose dependence was seen in the expression of apoptosis related proteins.. The sustained irradiation of ³²P-CP-PLLA microparticles can direct kill the VX2 tumor cell, thus the glycolysis of which were suppressed. Although the alive tumor cells still presented faraway from the microparticle, the expression of apoptosis related proteins in which were significantly different from the control. Bcl-2 and bax gene were induced to participate in regulation for the apoptosis of VX2 tumor cell by ionizing radiation from ³²P-CP-PLLA microparticles, so that the tumor growth was inhibited.

Topics: Animals; Apoptosis; Brachytherapy; Chromium Compounds; Disease Models, Animal; Female; Fluorodeoxyglucose F18; Humans; Lung Neoplasms; Male; Phosphates; Phosphorus Radioisotopes; Positron-Emission Tomography; Rabbits; Random Allocation; Tomography, X-Ray Computed

The objective of this study was to design and evaluate a 32P patch for the treatment of skin diseases.. The patch was prepared from chromic phosphate 32P and silicone. Bioelimination and biodistribution in healthy and treated animals, and the therapeutic efficacy of two treatment schemes (single dose and fractionated dose) in an animal model of skin cancer were studied.. Based on the bioelimination and biodistribution studies, no leakage of 32P from the patch was observed. The treated tumors reduced their mean diameter compared to controls. The single-dose therapeutic scheme showed a higher number of complete and partial remissions compared to the fractionated scheme. These results were confirmed by histopathological analysis of the samples.. The 32P patch was designed and produced according to specifications for the treatment of superficial lesions of the skin. Although the 32P patch is an open source, it behaves like a sealed one for use in brachytherapy treatments.

Topics: Administration, Cutaneous; Animals; Brachytherapy; Disease Models, Animal; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Female; Metabolic Clearance Rate; Mice; Phosphorus Radioisotopes; Skin Neoplasms; Tissue Distribution; Treatment Outcome

The treatment of urethral strictures represents an unsolved urological problem.. The effect of a (32)P-coated urethral catheter in the sense of low-dose rate brachytherapy to modulate wound healing will be analyzed in an animal experiment.. Unfortunately it is not possible to present any results because this is being studied for the first time and there are no experiences with low-dose rate brachytherapy and this form of application in the lower urinary tract. Furthermore the animal experiment will only start in the near future. Both decade-long experiences with radiotherapy to treat benign diseases and our own results of previous studies in otolaryngology and ophthalmology let us expect a significantly lower formation of urethral strictures after internal urethrotomy.. This study will contribute to improving the treatment of urethral strictures as demanded in previous papers.

Topics: Animals; Beta Particles; Brachytherapy; Catheters, Indwelling; Disease Models, Animal; Male; Phosphorus Radioisotopes; Rabbits; Radiotherapy Dosage; Recurrence; Tomography, Optical Coherence; Urethra; Urethral Stricture

For the systemic treatment of colorectal cancer, 5-fluorouracil (FU)-based chemotherapy is the standard. However, only a subset of patients responds to chemotherapy. Breathing of carbogen (95% O2 and 5% CO2) may increase the uptake of FU through changes in tumor physiology. This study aims to monitor in animal models in vivo the effects of carbogen breathing on tumor blood plasma volume, pH, and energy status, and on FU uptake and metabolism in two colon tumor models C38 and C26a, which differ in their vascular structure and hypoxic status. Phosphorus-31 magnetic resonance spectroscopy (MRS) was used to assess tumor pH and energy status, and fluorine-19 MRS was used to follow FU uptake and metabolism. Advanced magnetic resonance imaging methods using ultrasmall particles of iron oxide were performed to assess blood plasma volume. The results showed that carbogen breathing significantly decreased extracellular pH and increased tumor blood plasma volume and FU uptake in tumors. These effects were most significant in the C38 tumor line, which has the largest relative vascular area. In the C26a tumor line, carbogen breathing increased tumor growth delay by FU. In this study, carbogen breathing also enhanced systemic toxicity by FU.

Topics: Animals; Antimetabolites, Antineoplastic; Carbon Dioxide; Cell Line, Tumor; Colonic Neoplasms; Disease Models, Animal; Fluorine Radioisotopes; Fluorouracil; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neovascularization, Pathologic; Oxygen; Phosphorus Radioisotopes; Plasma; Radiation-Sensitizing Agents; Respiration

Poor stent-graft (SG) incorporation into the vessel wall, following endovascular repair of abdominal aortic aneurysms (EVAR), can lead to endoleaks and SG migration. Low-dose radiation can prevent aneurysm recurrence after coil embolization, and has been associated with a "paradoxical" increase in neointima formation after stenting in a few studies. It was hypothesized that in situ beta radiation emitted from SG could improve its incorporation by preventing the persistence of circulating channels between the implant and the vessel wall and increasing neointima formation around the SG. Phosphorus 32 ((32)P, 200 or 400 kBq per SG (n = 6 each)) was ion implanted on the external surface of balloon-expandable SGs. Twelve radioactive and six non-radioactive SGs were deployed in iliac arteries of nine Mongrel dogs. Neointima formation inside the graft and the persistence of circulating flow through an artificial groove created during the endovascular procedure were assessed by follow-up imaging and by blinded, computerized histomorphometric analysis after animal sacrifice at 3 months. Occlusion occurred in four radioactive SGs. A lesser number of patent grooves was observed along high-activity SGs than along control SGs (1/3 versus 4/4). No difference in neointima formation was observed in radioactive and non-radioactive SGs. Alteration of external graft surface was observed after ion implantation. Ion implantation of (32)P on SGs does not seem to be a viable strategy to improve incorporation and prevent type-I endoleak after EVAR.

Topics: Aneurysm; Animals; Disease Models, Animal; Dogs; Microscopy, Electron, Scanning; Phosphorus Radioisotopes; Stents; Survival Rate

Chinese-herb nephropathy (CHN) is a progressive renal interstitial fibrosis initially reported after concomitant intake of an anorexigen, (dex)fenfluramine, and a Chinese herb ( Aristolochia fangchi) containing nephrotoxic and carcinogenic aristolochic acid (AA). We thus tested the possible enhancing effect of the active enantiomer dexfenfluramine (DXF) on AA nephrotoxicity in a rat model for CHN. Groups of 12 salt-depleted male Wistar rats received daily subcutaneous injections of 7 mg/kg body weight DXF (DXF group), 7 mg/kg body weight AA (AA group), a combination of the same doses of AA and DXF (AA+DXF group), or vehicle (control group) for up to 35 days. Six animals per group were killed on day 10 and the remaining six on day 35. Renal function was evaluated by determining serum creatinine and urinary leucine aminopeptidase activity. Histological evaluation of kidney samples was performed and tubulointerstitial injuries were semiquantified. The DXF group did not differ from controls for any parameter. Similarly elevated serum creatinine levels, decreased leucine aminopeptidase enzymuria, and renal lesions were observed in the AA and the AA+DXF groups after both 10 and 35 days. The formation of specific AA-DNA adducts in liver and renal tissue samples was assessed by the (32)P-postlabelling method. Specific AA-DNA adduct levels were significantly increased in kidney tissues from AA+DXF rats compared with AA rats. These functional and histological data suggest that DXF does not enhance AA nephrotoxicity in a rat model for CHN. Further investigations are needed to clarify the mechanism by which DXF may enhance AA-DNA adduct formation.

Topics: Animals; Aristolochic Acids; Autoradiography; Body Weight; Creatinine; Dexfenfluramine; Disease Models, Animal; DNA Adducts; Drug Synergism; Drugs, Chinese Herbal; Fibrosis; Injections, Subcutaneous; Kidney; Liver; Longevity; Male; Mutagens; Nephritis, Interstitial; Phosphorus Radioisotopes; Rats; Rats, Wistar; Serotonin Receptor Agonists

Beta radiation prevents recanalization after coil embolization. We sought to determine the effects of varying coil caliber, length, activity of 32P per centimeter of coil or per volume, and spatial distribution of coils on recanalization.. We studied the angiographic evolution of 81 canine maxillary, cervical, and vertebral arteries implanted with a variety of nonradioactive (n=29 arteries) or radioactive (n=52) devices. We compared 1- or 2-caliber 0.015 or 0.010 coils ion-implanted or not with 3 different activity levels (0.05 to 0.08, 0.06 to 0.12, 0.18 to 0.32 microCi/cm) of 32P and totaling 4, 8, and 16 cm in length for the same arterial volume. We also compared inhibition of recanalization by beta radiation delivered by stents, after coil occlusion proximal to or within the stent, with that delivered by coils placed within nonradioactive stents. We finally studied the angiographic evolution of canine lateral wall carotid aneurysms treated with 1 or 2 stents of various activity levels positioned inside the parent artery across the neck. Animals were killed at 4 and 12 weeks for macroscopic photography and pathological examination.. All arteries (29 of 29) occluded with nonradioactive devices were recanalized, while 49 of 52 arteries (94%) implanted with 32P devices were occluded at 4 weeks. All aneurysms treated with stents, radioactive or not, demonstrated residual filling of the sac or of channels leading to the aneurysms at follow-up angiography at 4 weeks.. The recanalization process found in the canine arterial occlusion model is minimally affected by coil caliber, number, and length or packing density. Beta radiation reliably inhibits this process, but thrombosis is an essential condition for the efficacy of a radioactive coil strategy.

Topics: Aneurysm; Animals; Arterial Occlusive Diseases; Arteries; Beta Particles; Carotid Artery Diseases; Carotid Artery Thrombosis; Carotid Artery, Common; Combined Modality Therapy; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Drug Implants; Embolization, Therapeutic; Endothelium, Vascular; Equipment Design; Maxillary Artery; Neck; Phosphorus Radioisotopes; Radiotherapy Dosage; Recurrence; Single-Blind Method; Stents; Vertebral Artery

The present study examined the role of source-centering and geographical miss in vascular brachytherapy. After implantation of 13 mm long stents, 38 coronary arteries in 13 pigs were randomly assigned to centered brachytherapy (n = 13), eccentric brachytherapy (n = 13), or no radiation (n = 12). Geographical miss was avoided by careful placement of a 27 mm (32)P beta-radiation source. Restenosis was quantified by angiography, histomorphometry, and intravascular ultrasound at 28 days. Source-centering led to a significant (P < 0.001) reduction of in-stent area stenosis (centered radiation, 12% +/- 5%; eccentric radiation, 37% +/- 21%; control arteries, 41% +/- 13%). Despite 7 mm coverage of the edge segments, radiation was found to induce edge stenosis due to neointima formation and constrictive vascular remodeling. We conclude that centered radiation was superior to eccentric radiation in reducing in-stent luminal narrowing while radiation-induced edge stenosis was still observed despite extension of the radiation zone to 7 mm beyond the stent edges.

Topics: Animals; Arteries; Beta Particles; Blood Vessel Prosthesis Implantation; Brachytherapy; Cardiac Catheterization; Combined Modality Therapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Disease Models, Animal; Erythrocytes; Follow-Up Studies; Models, Cardiovascular; Myocytes, Smooth Muscle; Phosphorus Radioisotopes; Severity of Illness Index; Stents; Swine; Treatment Outcome; Tunica Intima; Ultrasonography, Interventional; Ventricular Remodeling

The assessment of kidney viability before transplantation (with a view of discarding nonviable organs) remains an obstacle to confidently extending organ harvesting to marginal donors. In the present study phosphorus magnetic resonance spectroscopy was used to monitor metabolic changes in (31)P-containing metabolites in isolated porcine kidneys. After various warm ischemia times, the organs were stored at 0 degrees C. Time-dependent changes in the phosphomonoester/inorganic-phosphate ratio were recorded at 0 degrees C were shown to follow a biexponential decay. The first-order kinetic rate constant of the short-time decay was strongly dependent on the warm ischemia time, a result that was discreted in terms of the underlying biochemistry. The metabolic events responsible for the dramatic decrease in phosphomonoester/inorganic phosphate ratio that occur immediately after organ perfusion and storage, suggest that any procedure to minimize organ damage must occur immediately after harvesting.

Topics: Animals; Disease Models, Animal; Ischemia; Kidney; Kinetics; Magnetic Resonance Spectroscopy; Phosphorus; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Renal Circulation; Swine

This study aimed to create a pig model of heart failure secondary to severe aortic stenosis and to examine the relationship between the alterations in myocardial high-energy phosphate (HEP) metabolism and protein expression of creatine kinase (CK) isoforms.. Sixteen pigs with left ventricular hypertrophy (LVH) secondary to ascending aortic banding and 10 normal pigs (N) were studied. Myocardial protein levels of CK isoforms (Western blot), HEP levels, and CK kinetics ((31)P MR spectroscopy) were measured under basal conditions. Nine of the 16 animals with LVH developed congestive heart failure (CHF), as evidenced by ascites (100 to 2000 mL). LV weight/body weight ratio (g/kg) was 2.18+/-0.15 in N hearts, 3.04+/-0.14 in hearts with LVH (P<0.01), and 4.23+/-0.36 in hearts with CHF (P<0.01 versus LVH). Right ventricle weight/body weight ratio and LV end-diastolic pressure were significantly higher in hearts with CHF (each P<0.01 versus N or LVH). Myocardial phosphocreatine/ATP ratios and the CK forward flux rates were decreased in LVH hearts, most severely in hearts with CHF. CK-M/beta-actin ratios were 2.21+/-12 (N), 1.69+/-0.15 (LVH), and 1.39+/-0.27 (CHF, P<0.05 versus N). CK-mitochondria (CK-Mt)/beta-actin ratios were 1.40+/-0.09 (N), 1.24+/-0.09 (LVH), and 1.02+/-0.08 (CHF, P<0.05 versus N or LVH). The severity of the reduction of CK flux rate was linearly related to the severity of the decrease of CK-Mt/beta-actin (r=0.68, P<0.01).. In this new model of heart failure/hypertrophy, the abnormal myocardial HEP metabolism is related to the decreased CK-Mt protein level, which in turn is related to the severity of the hypertrophy.

Topics: Adenosine Triphosphate; Animals; Aortic Valve Stenosis; Binding, Competitive; Biomarkers; Biopsy; Blood Pressure; Chromium; Creatine Kinase; Disease Models, Animal; Energy Metabolism; Heart Failure; Heart Rate; Hypertrophy, Left Ventricular; Kinetics; Magnetic Resonance Imaging; Phosphates; Phosphorus Radioisotopes; Protein Isoforms; Regional Blood Flow; Swine; Ventricular Dysfunction, Left

Radioactive stents have been reported to reduce in-stent neointimal thickening. An unexpected increase in neointimal response was observed, however, at the stent-to-artery transitions, the so-called "edge effect." To investigate the factors involved in this edge effect, we studied stents with 1 radioactive half and 1 regular nonradioactive half, thereby creating a midstent radioactive dose-falloff zone next to a nonradioactive stent-artery transition at one side and a radioactive stent-artery transition at the other side.. Half-radioactive stents (n=20) and nonradioactive control stents (n=10) were implanted in the coronary arteries of Yucatan micropigs. Animals received aspirin and clopidogrel as antithrombotics. After 4 weeks, a significant midstent stenosis was observed by angiography in the half-radioactive stents. Two animals died suddenly because of coronary occlusion at this mid zone at 8 and 10 weeks. At 12-week follow-up angiography, intravascular ultrasound and histomorphometry showed a significant neointimal thickening at the midstent dose-falloff zone of the half-radioactive stents, but not at the stent-to-artery transitions at both extremities. Such a midstent response (mean angiographic late loss 1.0 mm) was not observed in the nonradioactive stents (mean loss 0.4 to 0.6 mm; P< 0.01).. The edge effect of high-dose radioactive stents in porcine coronary arteries is associated with the combination of stent injury and radioactive dose falloff.

Topics: Animals; Blood Vessel Prosthesis Implantation; Coronary Angiography; Coronary Vessels; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Radiation; Drug Implants; Female; Graft Occlusion, Vascular; Implants, Experimental; Phosphorus Radioisotopes; Stents; Swine, Miniature; Tunica Intima; Vascular Patency

Bisphosphonates, potent inhibitors of bone resorption, have been used clinically to correct the continued loss of bone mass in osteoporosis and in other conditions. However, there has been some concern that long-term treatment with these compounds, as well as more recently developed drugs, may also decrease the rate of bone formation. Bisphosphonates, which are strongly bound to hydroxyapatite crystals, may alter the structure and reactivity of the crystals, interfere with new crystal nucleation and growth, as well as alter the short-range order of newly formed crystals. We have investigated the chemistry and structure of the solid calcium-phosphate mineral phase of lumbar vertebrae of ovariectomized, 6.5-month-old rats treated with bisphosphonates for 1 year after onset of osteopenia. Appropriate control groups were used for comparison. The techniques used to assess the mineral phase were chemical analyses, Fourier transform-infrared (FT-IR) and FT-Raman spectroscopy, FT-IR microspectroscopy, and phosphorus-31 magic-angle-sample spinning nuclear magnetic resonance spectroscopy ((31)P MAS NMR). The (31)P MAS NMR spectra of trabecular bone of lumbar vertebrae of control, ovariectomized, and treated animals were similar. However, there were several significant differences in the results obtained by FT-IR spectroscopy of the whole tissue samples, FT-IR microspectroscopy of sections of bone, and chemical analyses. For example, whereas chemical analyses demonstrated that the CO(3) content of the mineral phase of the ovariectomized animals was decreased compared with controls, FT-IR microspectroscopy of bone sections showed no changes in the relative CO(3) content, but some changes in the environment of the CO(3) groups. However, chemical analyses of the crystals, combined with data from all three spectroscopic methods and with data from serum analysis, did indicate small changes in the mineral phase after ovariectomy, corrected after treatment with bisphosphonates. In any event, the chemical and structural data in the present studies demonstrate that the bisphosphonate, tiludronate, does not significantly alter the mineral components of bone after 1 year of treatment during the course of which bone loss was reversed.

Topics: Animals; Apatites; Bone Diseases, Metabolic; Bone Resorption; Calcium; Cholecalciferol; Diphosphonates; Disease Models, Animal; Female; Lumbar Vertebrae; Magnetic Resonance Spectroscopy; Ovariectomy; Parathyroid Hormone; Phosphorus; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Weight Loss

The arterial placement of (32)P beta-particle-emitting stents in various experimental animal models results in discordant effects on neointimal formation. We studied the vascular effects of beta-particle-emitting stents in normal canine coronary arteries because compared with pigs and rabbits, the canine model may more closely mimic the vascular response of humans.. Thirty stents (control nonradioactive, n=10; low-activity (32)P, 3.5 to 6.0 microCi, n=11; high-activity (32)P, 6.5 to 14.4 microCi, n=8) were implanted in normal canine coronary arteries through the use of a single balloon inflation at nominal pressure. Histological analysis after 15 weeks included the measurement of neointimal and adventitial area and thickness. Neointimal fibrin area was measured with the use of computer-assisted color segmentation on Movat pentachrome sections. Luminal stenosis was significantly increased in (32)P stents compared with control stents (44.6+/-16.8% versus 32.7+/-10.8%; P=0.05) and was highest in the high-activity group (45.5+/-24.3%). No evidence of an "edge effect" was seen in adjacent, nonstented coronary segments. All (32)P stents showed incomplete vascular healing as indicated by a dose-dependent increase in fibrin area with increasing stent activity. Arterial radiation resulted in a decrease in adventitial size, which was maximal for high-activity (32)P stents, indicating an inhibitory effect on the adventitial response to injury.. (32)P beta-particle-emitting stents have adverse vascular effects at 15 weeks in the canine normal coronary artery model. Vascular brachytherapy with this device causes increased neointimal formation and prominent, dose-dependent lack of healing.

Topics: Animals; Brachytherapy; Coronary Vessels; Disease Models, Animal; Dogs; Dose-Response Relationship, Radiation; Fibrin; Male; Myocardial Revascularization; Phosphorus Radioisotopes; Stents; Tunica Intima

To determine whether gene delivery by means of a synthetic no viral DNA delivery system that is capable of gene transfer can be mapped with magnetic resonance (MR) imaging.. The DNA delivery system consisted of aminated (poly-L-lysine-conjugated) dextran chains anchored together with a central superparamagnetic core. Three different types of constructs were synthesized that differed in their amino content and, thus, DNA-loading capacity. The model plasmid consisted of complementary DNA encoding for humanized green fluorescent protein. Constructs were tested in cell culture and in vivo in a rat model.. All three constructs were capable of transfecting human cells in culture with transfection efficiencies ranging from 0.3% to 4.1%, which is similar to that of diethylaminoethyl-dextran. MR imaging experiments showed that DNA constructs induced signal intensity changes that co-localized with phosphorus-33-labeled plasmid distribution at autoradiography. After injection of the constructs into the corpus callosum of rats, weak green fluorescent protein expression of neuronal and glial cells could be detected at immunohistologic examination.. Dextran-based nonviral DNA delivery systems are capable of transfecting cells and can be visualized with MR imaging.

Topics: Amino Acids; Animals; Autoradiography; Brain; Cells, Cultured; Corpus Callosum; DEAE-Dextran; Dextrans; Disease Models, Animal; DNA, Complementary; Fluorescent Dyes; Gene Expression Regulation; Gene Transfer Techniques; Genetic Markers; Genetic Vectors; Humans; Magnetic Resonance Imaging; Neuroglia; Neurons; Phosphorus Radioisotopes; Plasmids; Polylysine; Protein Biosynthesis; Proteins; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Transfection

The models of local radiation injuries of skin--radiation ulcer, radiation epidermitis, radiation dermatitis in guinea-pigs and rabbits are developed. Experimental reproduction local radiation injuries by different doses, regimes and spices of ionizing irradiation was carried out. Detailed description of radiation action on skin is given. Pathomorphologic characteristic of radiation ulcers is given. Models may be used for pathogenesis learning and experimental therapy of local skin radiation injures.

Topics: Animals; Beta Particles; Disease Models, Animal; Dose-Response Relationship, Radiation; Guinea Pigs; Phosphorus Radioisotopes; Rabbits; Radiation Injuries, Experimental; Radiodermatitis; Skin; X-Rays

Creutzfeldt-Jakob Disease (CJD), a neurodegenerative and dementing disease of later life, is caused by a viruslike entity that is incompletely characterized. As in scrapie, all more purified infectious brain preparations contain nucleic acids. However, it has not been possible to visualize unique bands that may derive from a viral genome. We here used a subtractive strategy known as representational difference analysis (RDA) to uncover such sequences. To reduce the complexity of starting target nucleic acids, sucrose gradients were first used to select nuclease resistant particles with a defined 120S size. In CJD this single 120S gradient peak is highly enriched for infectivity, and contains reduced amounts of PrP (Proc. Natl. Acad. Sci. 92, 5124-8, 1995). Parallel 120S fractions from uninfected brain were made to generate subtractor sequences. 120S particles were lysed in GdnSCN, and ng amounts of released RNA were purified for random-primed cDNA synthesis. To capture representative fragments of 100-500 bp, cDNAs were cleaved with Mbo I for adaptor ligation and amplification. In the first experiment with moderate RDA selection, it was possible to visualize clones from CJD cDNA that did not hybridize to control cDNA. In the second experiment, more exhaustive subtractions yielded a discrete set of CJD derived gel bands. Competitive hybridization showed a subset of these bands were not present in either the control 120S cDNA or in the hamster genome. This represents the first demonstration of apparently CJD-specific nucleic acid bands in more purified infectious preparations. Although exhaustive cloning, sequencing and correlative titration studies need to be done, it is encouraging that most of the viral candidates selected thus far have no significant homology with any previously described sequence in the database.

Topics: Animals; Brain Chemistry; Cloning, Molecular; Creutzfeldt-Jakob Syndrome; Cricetinae; Disease Models, Animal; DNA, Complementary; DNA, Viral; Gene Amplification; Genetic Testing; Nucleic Acid Hybridization; Phosphorus Radioisotopes; Polymerase Chain Reaction

The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo 31P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 +/- 0.05 at the onset and 7.15 +/- 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.

Topics: Animals; Animals, Newborn; Brain; Disease Models, Animal; Energy Metabolism; Hypoglycemia; Insulin; Magnetic Resonance Spectroscopy; Phosphocreatine; Phosphorus Radioisotopes; Swine

The aim of this study was to evaluate the therapeutic possibilities of radiolabeled antisense oligodeoxynucleotides. The internal radiation dose from known cellular and animal data was calculated, and the suitability of different phosphorus isotopes as labels for oligonucleotides was assessed. We calculated the pharmacokinetics and tissue distribution in vivo of short oligodeoxynucleotide phosphorothioates by using the data from two different radionuclides: phosphorus-33 (t1/2 = 24.4 days, maximum beta-energy = 250 ke V) and phosphorus-32 (t1/2 = 14.3 days, maximum beta-energy = 2270 ke V). The absorbed doses of 32P-labeled and 33P-labeled oligonucleotides were estimated using the published biodistribution data for several oligonucleotides in animal models for both tumor xenografts and AIDS. The local absorption of 33P was higher than that of 32P if the radius of the spherical distribution of activity was smaller than approximately 500 microns. In a mouse tumor xenograft model, an intravenously injected activity of 1 MBq achieved sufficient radiation doses in the tumor; 11 Gy for 32P and 1.5 Gy for 33P were obtained. In normal organs in the same model, the liver doses were 5.0 Gy (32P) and 0.7 Gy (33P), and the kidney doses were 14 Gy (32P) and 2.0 Gy (33P). We conclude that 33P may have more beneficial radiotherapeutic characteristics for oligonucleotides than 32P. This method could be applied on the macroscopic, cellular, and subcellular levels and help to design further experimental studies for the use of oligonucleotide radiotherapy and phosphorothioate probes.

Topics: Acquired Immunodeficiency Syndrome; Animals; Disease Models, Animal; Kidney; Liver; Mice; Oligonucleotides, Antisense; Phosphorus Radioisotopes; Radiotherapy Dosage; Rats; Thionucleotides; Tissue Distribution; Tumor Cells, Cultured

The physiological and therapeutic effects of the bioreductive agent RSU1069 (80 mg/kg i.p.) and its prodrug RB6145 (240 mg/kg i.p.) were investigated in the SCCVII tumour. Using laser Doppler flowmetry it was found that RSU1069 produced a significant 30% reduction in tumour blood flow 30 min after administration, while RB6145 had no effect. Tumour oxygenation, measured with an Eppendorf oxygen electrode, was unchanged by either agent except for a reduction in values less than 2.5 mmHg at 30 min after injection. Neither agent significantly altered tumour energy metabolism, assessed by 31P magnetic resonance spectroscopy. Both agents significantly increased tumour glucose content by a factor of 1.6-1.7 at 30 min after injection, but had no effect on glucose-6-phosphate or lactate levels. Tumour growth was significantly delayed by heating (42.5 degrees C, 60 min), and although neither RSU1069 nor RB6145 alone had any effect on tumour growth they produced a similar enhancement of the tumour response to heat. The therapeutic effects are consistent with the known conversion in vivo of one third of the pro-drug RB6145 to its active product RSU1069, however the physiological effects of the two agents in the SCCVII tumour are not identical.

Topics: Animals; Antineoplastic Agents; Carcinoma, Squamous Cell; Disease Models, Animal; Female; Magnetic Resonance Spectroscopy; Male; Mice; Mice, Inbred C3H; Misonidazole; Neovascularization, Pathologic; Nitroimidazoles; Oxygen; Phosphorus Radioisotopes

A study of the protective efficiency imparted by intermittent warm blood cardioplegia (WBCP) using perfused rat heart model.. Hemodynamic parameters were monitored simultaneously with metabolic changes in high-energy phosphates using 31P-NMR spectroscopy. Following 30 min perfusion with Krebs-Henseleit (KH) buffer, all hearts were arrested for one hour (G1 and G2) and than reperfused with KH for 30 minutes. A warm oxygenated crystalloid cardioplegia (WCCP, modified St Thomas' hospital solution) was used for the control group (G1). The second group of hearts (G2) were arrested with oxygenated WBCP (K+ = 15 mM; Hct = 15-20%) and the third group (G3), was subjected to a protocol consisting of 4 periods (10 min each) of WBCP interspersed by 10 min of global ischaemia.. The post-arrest percentage recoveries of LVDP, +dP/dt and HR were respectively: 88, 93 and 90 for G1 (n = 8); 97, 100 and 98 for G2 (n = 10); 76, 79 and 91 for G3 (n = 12). The corresponding metabolic recoveries of ATP and PCr were respectively, 85 and 90 for G1; 91 and 98 for G2 and 73 and 85 for G3. The PCr level declined during the arrest period in G1 contrasting with elevated PCr level (> 140%) during the WBCP arrest in G2. After an initial rise to approximately 140%, PCr level gradually decreased during the intermittent WBCP interval (G3).. At normothermia, with equal CF rates, continuous WBCP provides better myocardial protection, through an effective oxygen supply, compared with WCCP. During the intermittent periods of ischaemia, certain metabolic and hemodynamic dysfunction occurs.

Topics: Animals; Chemotherapy, Cancer, Regional Perfusion; Disease Models, Animal; Heart; Heart Arrest, Induced; Hemodynamics; Magnetic Resonance Spectroscopy; Myocardial Ischemia; Phosphorus Radioisotopes; Rats; Rats, Sprague-Dawley

Vincristine is one of the cytostatic drugs present in cocktails commonly used for the treatment of cancer in children. The aim of this study was to evaluate biochemically and histologically the toxic effects of this drug on the developing tooth in vitro using the organ culture model in order to be able to predict what damage the drug can induce in the developing teeth from children undergoing anti-neoplastic chemotherapy. The most profound effect of the drug (10(-8)M-10(-4)M vincristine) on the developing tooth germ was the induction of mitotic arrests at the cervical loop and in the inter-cuspal regions. The 10(-4)M-10(-6)M vincristine doses were cytotoxic to most cells in the developing tooth germ. The 10(-7)M vincristine dose apart from induction of mitotic arrests, did not appear to be cytotoxic to the mature differentiated secretory cells. However, this dose induced incomplete nuclear polarization of the differentiating ameloblasts and odontoblasts. At 10(-8)M vincristine, the only effect observed were mitotic arrests; the secretory cells did not appear to have been affected at all. On the other hand, mineralization (TCA-soluble 45Ca and 32P uptake) was dose-dependently decreased from 10(-7)M vincristine upwards. 10(-9)M vincristine, the lowest dose tested, did not induce any changes in the developing tooth germ. The organ culture data indicate that 10(-9)M vincristine is the highest (safe) dose which does not induce any toxic effects in the developing hamster tooth germ.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Ameloblasts; Animals; Calcium; Calcium Radioisotopes; Cell Differentiation; Cell Nucleus; Cricetinae; Disease Models, Animal; Dose-Response Relationship, Drug; Enamel Organ; Mitosis; Odontoblasts; Organ Culture Techniques; Phosphorus; Phosphorus Radioisotopes; Tooth Calcification; Tooth Germ; Vincristine

Cultures of retinal pigment epithelium (RPE) from normal Long-Evans (LE) and dystrophic Royal College of Surgeons (RCS) rats were incubated with 32P-orthophosphate and then phagocytically challenged with isolated rod outer segments (ROS) or polystyrene latex spheres (PSL). The 32P incorporation into individual proteins was quantified by image analysis of two-dimensional gel autoradiograms, and changes in phosphorylation were identified by comparison with unchallenged control cultures. Phosphorylation changes that were similar in response to either ROS or PSL were classified as nonspecific and omitted from further analysis; those associated solely with ROS exposure were classified as ROS specific and compared between the two strains. None of the 30 ROS-specific changes in protein phosphorylation identified in normal LE RPE were the same as in RCS RPE. However, unique ROS-specific changes in phosphorylation were observed in 13 RCS RPE proteins. Three RCS proteins showed ROS-specific decreases; ten showed ROS-specific increases. Six of these ten RCS proteins with increased phosphorylation showed ROS-specific decreases in LE RPE. No other correspondence in ROS-specific changes was found among the remaining LE or RCS RPE proteins, but several RCS proteins were phosphorylated at abnormal levels under control conditions. Even though ROS-induced changes in phosphorylation were aberrant in RCS RPE, their presence indicated that a ROS-specific transmembrane signal was generated after interaction with ROS. The abnormal increases and decreases observed in ROS-specific phosphorylation in the RCS suggested that the defect in ROS phagocytosis was associated with the misregulation or malfunction of both protein kinases and phosphatases.

Topics: Animals; Disease Models, Animal; Electrophoresis, Gel, Two-Dimensional; Eye Proteins; Methionine; Microspheres; Phagocytosis; Phosphorus Radioisotopes; Phosphorylation; Pigment Epithelium of Eye; Rats; Rats, Mutant Strains; Retinal Degeneration; Rod Cell Outer Segment; Sulfur Radioisotopes

To determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 microgram/kg per min), used to increase heart rate x systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption. Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p less than 0.05) even though changes in hemodynamic and functional variables were similar in both groups. These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Chronic Disease; Creatine Kinase; Disease Models, Animal; Dogs; Echocardiography; Epinephrine; Heart; Hypertension, Renovascular; Kinetics; Magnetic Resonance Spectroscopy; Myocardium; Phosphocreatine; Phosphorus Radioisotopes

Thrombolytic therapy has increased the need for a technique to assess the viability of recently reperfused myocardium. This study examined the ability of in vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy to distinguish reperfused-viable (stunned) from reperfused-infarcted myocardium at 6, 30, and 54 hours following coronary artery occlusion in a canine model. A 15-minute occlusion produced reperfused-viable myocardium in five animals and a 360-minute occlusion produced reperfused-infarcted myocardium in six animals. Postreperfusion risk zone myocardial phosphocreatine (PCr) concentration measured by P-31 NMR spectroscopy was significantly depressed throughout the 3-day study period in infarcted but not in viable myocardium (p less than 0.01 between groups, all time points). The postreperfusion ratio of inorganic phosphate (Pi) to PCr concentration, as determined by NMR spectroscopy, was elevated throughout the study period in infarcted but not in viable reperfused myocardium (p less than 0.01 between groups, all time points). Postreperfusion Pi concentration was elevated at 6 hours but not subsequently in reperfused-infarcted myocardium, and was not elevated in reperfused-viable myocardium. Logistic regression models selected PCr concentration and the Pi/PCr ratio as providing the best discrimination between reperfused-viable and reperfused-infarcted myocardium. The accuracy of P-31 NMR variables selected by logistic regression analysis for determining myocardial viability ranged from 97% to 100%.

Topics: Animals; Coronary Circulation; Coronary Disease; Diagnosis, Differential; Disease Models, Animal; Dogs; Magnetic Resonance Spectroscopy; Myocardial Infarction; Myocardial Reperfusion; Phosphorus Radioisotopes; Regression Analysis; Time Factors

In various models of hypertension of genetic origin, a hypersensitivity of phospholipase C has been demonstrated to participate in the hyperreactivity of platelets toward a variety of vasoactive agents. Since this abnormality could not be observed in the absence of cell stimulation, it could not account for the increase in free Ca2+ which has been reported in resting platelets in primary hypertension. Likewise, in hypertensive subjects, platelets behave hyperactive when stimulated by ADP, although the stimulus has been demonstrated to be a poor activator of phospholipase C. In order to gain insight into the membrane alteration that could account for the cellular hyperactivity which characterizes hypertensive subjects, we investigated, in resting platelets, the kinetics of radioactive labeling of major membrane phospholipids. Isolated platelets were prepared from SHR (4w and 17w of age), SHR-SP, Dahl salt-resistant and salt-sensitive rats fed either a low or a high salt diet, DOCA-salt hypertensive rats and from the appropriate normotensive controls. Irrespective of the radioactive precursor used (32P-orthophosphate, 3H-glycerol, 3H-choline), the labeling of phosphatidylcholine (PC) was markedly (up to 20 fold) enhanced in SHR (whichever their age) and SHR-SP compared with WKY. This increase, specific of PC, could not be accounted for by differences either in the actual amount of PC or in the uptake of various labels, suggesting an increased PC turnover. Such an increase was also observed in platelets of Dahl hypertensive rats but not in those of DOCA-salt hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Blood Platelets; Cell Membrane; Disease Models, Animal; Hypertension; Phosphatidylcholines; Phosphorus Radioisotopes; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Longitudinal study of metabolic change after cerebral infarction was done using nuclear magnetic resonance spectroscopy (MRS). Localized completed infarction model induced by intra-cranial ligation of the middle cerebral artery and extra-cranial ligation of common carotid artery in rats was utilized. In acute study the proton MRS revealed a sharp increase of lactic acid but the phosphorus -31 MRS did not show prominent changes. This increase of lactic acid persists 24 hours after the induction of infarction. In chronic study the spectroscopic pattern of the infarcted brain showed minimum difference from the control normal brain. However the signal intensity of phosphomonoester was significantly higher in the infarcted brain. Our study in acute phase suggests that the proton MRS is a sensitive probe to detect an early metabolic deterioration induced by ischemic insult. And the increase of phosphomonoester in chronic infarcted brain may imply that a gliosis seen in chronic infarction has a metabolic resemblance to neonate brain and neoplasm.

Topics: Animals; Brain; Cerebral Infarction; Disease Models, Animal; Energy Metabolism; Lactates; Lactic Acid; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphorus Radioisotopes; Protons; Rats; Rats, Inbred Strains

The purpose of this study was to quantitate the intracellular high-energy phosphate compounds during 6 hours of tissue ischemia in the anterior tibial compartment of beagles subjected to an induced traumatized compartment syndrome. The goal of this work was to provide clinicians with objective criteria to augment clinical judgment regarding surgical intervention in the impending compartment syndrome. A beagle model was utilized in which the Delta pressure (difference between the mean arterial pressure and compartment pressure) could be controlled. The model, in conjunction with 31P-magnetic resonance spectroscopy (MRS), allowed a measure of high-energy phosphate compounds and pH in the compartment at various Delta pressures. The extent of ischemic metabolic insult in the compartment was then quantitated. Our data suggest the following: 1) lower Delta pressures result in a proportionally greater drop in the intracellular phosphocreatine ratio and pH; 2) at lower Delta pressures, there is proportionally greater decline in the percentage recovery post-fasciotomy; 3) blood pressure is extremely important and periods of hypotension may result in increased muscle damage at lower compartment pressures.

Topics: Animals; Anterior Compartment Syndrome; Blood Pressure; Compartment Syndromes; Disease Models, Animal; Dogs; Energy Metabolism; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Microscopy, Electron; Muscles; Phosphorus; Phosphorus Radioisotopes; Time Factors

The first nuclear magnetic resonance spectroscopic study of the canine pancreas is described. Both in-vivo, ex-vivo protocols and nmr observables are discussed. The stability of the ex-vivo preparation based on the nmr observables is established for at least four hours. The spectra obtained from the in-vivo and ex-vivo preparations exhibited similar metabolite ratios, further validating the model. Metabolite levels were unchanged by a 50% increase in perfusion rate. Only trace amounts of phosphocreatine were observed either in the intact gland or in extracts. Acute alcoholic pancreatitis was mimicked by free fatty acid infusion. Injury resulted in hyperamylasemia, edema (weight gain), increased hematocrit and perfusion pressure, and depressed levels of high energy phosphates.

Topics: Alcoholism; Animals; Disease Models, Animal; Dogs; Magnetic Resonance Spectroscopy; Oleic Acid; Oleic Acids; Pancreas; Pancreatitis; Phosphocreatine; Phosphorus Radioisotopes

The mechanism of Ca2+ overload production in ischaemia-reperfusion of the heart is unclear. The present study was designed to examine whether loss of second messenger (Ca2+ and cyclic AMP) control of sarcolemmal Ca2+ transport systems occurs during ischaemia. Ischaemic (1, 2 and 3 h duration) and non-ischaemic tissue samples were taken from the coronary-ligated porcine heart and a membrane fraction, enriched in sarcolemmal vesicles, was isolated. The membranes were phosphorylated using [gamma-32P] ATP in the presence of either cyclic AMP or Ca2+-calmodulin. The in vitro 32P incorporation into the electrophoretically separated phospholamban-like protein, became markedly reduced depending on the duration of ischaemia. The reduction could neither be attributed to factors as ischaemia-induced changes in membrane-bound kinase or phosphatase nor in situ phosphorylation of phospholamban. It is postulated that during ischaemia and reperfusion, a deficient control of the sarcolemmal Ca2+ pump by phospholamban-like protein may serve as a source of intracellular Ca2+ overload.

Topics: Adenosine Triphosphate; Animals; Calcium; Calcium-Binding Proteins; Coronary Disease; Cyclic AMP; Disease Models, Animal; Phosphoprotein Phosphatases; Phosphoproteins; Phosphorus Radioisotopes; Phosphorylation; Proteins; Swine

Topics: Animals; Disease Models, Animal; Eye; Hypersensitivity; Phosphorus Radioisotopes; Rabbits; Time Factors; Uveitis

Topics: Acetylcholine; Animals; Brain Chemistry; Choline; Chromatography, Gas; Corpus Striatum; Deanol; Disease Models, Animal; Ethanolamines; Huntington Disease; Kainic Acid; Male; Phosphorus Radioisotopes; Pyrrolidines; Rats

Topics: Animals; Cobalt Radioisotopes; Disease Models, Animal; Female; Injections, Intraperitoneal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C3H; Neoplasm Metastasis; Neoplasm Transplantation; Osteosarcoma; Ovarian Neoplasms; Peritoneal Neoplasms; Phosphorus Radioisotopes; Radioisotope Teletherapy; Sarcoma, Experimental

The pulmonary response to a bacteremic challenge was studied in a mouse model. The distribution of intravenously injected radiotracer-labeled Proteus mirabilis and Staphylococcus aureus in the lungs, liver, spleen, kidney, and blood was examined at 0, 5 30, 60, and 240 min. Pulmonary killing of these organisms was studied at 0, 30, and 240 min; 0.8 plus or minus 0.1 per cent of the P. mirabilis and 1.5 plus or minus 0.2 per cent of the S. aureus remained within the lungs after 4 hours. Although only 2.2 plus or minus 0.2 per cent of the P. mirabilis organisms were alive, 33.8 plus or minus 8.8 per cent of the staphylococci remained viable after this period. Light and electron micographs verified that polymorphonuclear leukocytes phagocytized these bacteria. The defense mechanisms of the lung against bloodborne and airborne bacterial infection are functionally, as well as morphologically, distinct.

Topics: Animals; Blood Bactericidal Activity; Disease Models, Animal; Injections, Intravenous; Kidney; Leukocytes; Liver; Lung; Male; Mice; Microscopy, Electron; Organ Size; Phagocytosis; Phosphorus Radioisotopes; Proteus mirabilis; Sepsis; Spleen; Staphylococcus; Sulfur Radioisotopes

Topics: Adenylyl Cyclases; Adipose Tissue; Animals; Diabetes Mellitus; Disease Models, Animal; Epinephrine; Lipid Metabolism; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Phosphoric Diester Hydrolases; Phosphorus Radioisotopes; Tritium