Acute choke zone effects: Lessons from radioactive and fluorescent microspheres in a pig model muscle flap.

BACKGROUND: Choke vessels dilate and contract to regulate blood flow between adjacent arterial angiosomes. In skin flap surgery, when arterial inflow to an angiosome is ligated, choke vessels allow blood supply from an adjacent angiosome. In muscle flap surgery, the vascular anatomy is analogous to skin flaps; however, while it is established that the choke vessels will fully dilate irreversibly after two to three days, no study has yet analyzed the acute changes in each vascular region immediately following ligation of one pedicle. OBJECTIVE: To establish whether the choke vessels open or close immediately following ligation of a pedicle, and how this change affects blood flow in the adjacent proximal and distal vascular regions. METHODS: Radioactive and fluorescent microspheres in a pig model were used to study the regional intramuscular blood flow in each anatomical zone of a rectus abdominis flap. Blood flow measurements for each zone were calculated relative to the entire muscle at preligation, ligation and various times (15 min to 90 min) postligation. RESULTS: There was no statistically significant difference in blood flow across choke zones as a result of ligation. This signifies that the choke vessels do not significantly dilate to produce a statistically significant measureable change in blood flow. CONCLUSIONS: Given these results and previous literature findings, the anatomical presence of choke vessels in a muscle is the strongest determining factor for acute flap viability in surgery.

HISTORIQUE: Les vaisseaux anastomotiques se dilatent et se contractent pour réguler le débit sanguin entre les angiosomes artériels adjacents. Dans le cadre d'une chirurgie par lambeau cutané, lors de la ligature du débit artériel vers un angiosome, les vaisseaux anastomotiques assurent un débit sanguin en provenance d'un angiosome adjacent. L'anatomie vasculaire est alors analogue aux lambeaux cutanés. Cependant, bien qu'il soit établi que les vaisseaux anastomotiques se dilatent pleinement et de manière irréversible au bout de deux ou trois jours, aucune étude n'a encore analysé les changements aigus de chaque région vasculaire immédiatement après la ligature d'un pédicule. OBJECTIF: Établir si les vaisseaux anastomotiques s'ouvrent ou se ferment immédiatement après la ligature d'un pédicule et examiner l'effet de ce changement sur le débit sanguin des régions proximales et distales adjacentes. MÉTHODOLOGIE: Les chercheurs ont utilisé les microsphères radioactives et fluorescentes d'un porc pour étudier le débit sanguin intramusculaire régional de chaque zone anatomique d'un lambeau du grand droit. Ils ont mesuré le débit sanguin de chaque zone par rapport au muscle entier avant la ligature, au moment de la ligature et à divers moments (de 15 à 90 minutes) après la ligature. RÉSULTATS: Il n'y avait pas de différence statistiquement significative du débit sanguin dans les diverses zones anastomotiques après une ligature. Ainsi, les vaisseaux anastomotiques ne se dilatent pas au point de produire un changement du débit sanguin pouvant être mesuré de manière statistiquement significative. CONCLUSIONS: Compte tenu de ces résultats et des conclusions de publications scientifiques, la présence anatomique de vaisseaux anastomotiques dans un muscle est le principal déterminant de viabilité aiguë d'un lambeau lors d'une chirurgie.

Biological evaluation of 2-fluoro-2-[123I]iodo-mannose (FIM): biological evaluation of FIM.

This paper describes the biodistribution of a radio-iodinated analog of fluorodeoxyglucose (FDG). 123I-2-fluoro-2-iodo-mannose (FIM) was investigated as a potential single photon emission tomography (SPECT) imaging agent. We also compare the results with the observed distribution of the classical PET agent 18F-FDG and newly developed 18F-difluorodeoxyglucose (DFDG). Following radioiodination, the final product was stable in-vitro for 24 hrs. Mice showed a rapid blood clearance and deiodination of the 123I-FIM reflected by high stomach and thyroid uptake. Comparison with 18F-FDG and 18F-DFDG revealed a large discrepancy between the 18F labeled sugars and the 123I-FIM biological distribution. The iodinated product was not found to be a metabolic marker for in-vivo studies.

Performance of the dynamic single photon emission computed tomography (dSPECT) method for decreasing or increasing activity changes.

Radionuclide imaging is now widely used whenever functional information is required. We present a new approach to dynamic SPECT imaging (dSPECT method) that uses a single slow rotation of a conventional camera and allows us to reconstruct a series of 3D images corresponding to the radiotracer distribution in the body at various times. Using simulations of various camera configurations and acquisition protocols, we have shown that this method is able to reconstruct washout half-lives with an accuracy greater than 90% when used with triple-head SPECT cameras. Accuracy decreases when using fewer camera heads, but dual-head geometries still give an accuracy greater than 80% for short and 90% for long half-lives and about 50-75% for single-head systems. Dynamic phantom experiments have yielded similar results. Presence of attenuation and background activity does not affect the accuracy of the dSPECT reconstructions. In all situations investigated satisfactory dynamic images were produced. A preliminary normal volunteer study measuring renal function was performed. The reconstructed dynamic images may be presented as a three-dimensional movie showing movement of the tracer through the kidneys and the measurement of the regional renal function can be performed. The time-activity curves determined from this dSPECT data are very similar to those obtained from dynamic planar scans.

Extending the lifetime of anticoagulant oligodeoxynucleotide aptamers in blood.

We have investigated (123)I and (125)I DNA aptamer analogs of anticoagulant DNA aptamers to thrombin exosite 1 and exosite 2 for thrombus imaging potential. Two severe problems are rapid clearance from circulating blood and blood nuclease. With aptamers (unlike antisense) the nucleotide analogs used in polymerase chain reaction-selection cycles also must be used in the radiotracer. We investigated 3'-biotin-streptavidin (SA) bioconjugates of the aptamers to alleviate these problems. Blood nuclease assays and biodistribution analysis were used in the mouse and rabbit. We found that 3'-biotin protected the aptamers significantly from blood nuclease in vitro, but it did not slow in vivo clearance. In contrast, the 3'-biotin-SA bioconjugates were resistant to blood nuclease in vitro and were also longer-lived (10-20 times) in vivo. Bioconjugate aptamers retained affinity for thrombin. Two solutions emerge: 1) In noncirculating blood (within a thrombus) 3'-biotin extends aptamer lifetime, whereas 2) in circulating blood (the transport medium), where more aggressive clearance is encountered, 3'-SA extends aptamer lifetime.

Chronotropic action of 5-hydroxytryptamine (5-HT) on colonic migrating motor complexes (CMMCs) in the isolated mouse colon.

The effects of 5-hydroxytryptamine (5-HT) and related drugs on colonic migrating motor complexes (CMMCs) were evaluated in isolated colons from the heterozygotes of pie-bald lethal mice. 5-HT produced a dose-related increase in the frequency of CMMCs without any change in the amplitude or duration of the CMMC contractions themselves. The 5-HT(2) agonist, alpha-methyl 5-HT, (100 nM-1 microM) increased the frequency of CMMCs whilst the 5-HT(3) agonist, 2-methyl 5-HT, did so at 10 microM. The 5-HT(4) agonist, 5-methoxy dimethyl tryptamine oxalate did not alter the frequency of CMMCs in the concentration range 1 nM-10 microM. The 5-HT(3) receptor antagonist, ondansetron, increased the interval between CMMCs in the concentration range 100 nM-1 microM, whilst the 5-HT(1) receptor antagonist, methiothepin, the 5-HT(2) receptor antagonist, cyproheptadine and the 5-HT(4) receptor antagonist, SDZ 205 557, had no significant effects on the interval between CMMCs in the concentration range 1 nM-10 microM. The effects of 5-HT did not appear to be altered by the presence of ondansetron (1 microM) or cyproheptadine (1 microM). However, in the presence of ondansetron (1 microM), the further addition of cyproheptadine (1 microM) effectively abolished CMMCs. Furthermore, in the combined presence of these antagonists the effects of 5-HT were severely diminished. It is suggested that the frequency of CMMCs may be under the influence of endogenously released 5-HT in this preparation

Different effects of strenuous eccentric exercise on the accumulation of neutrophils in muscle in women and men.

The purpose of this study was to evaluate the sex differences in delayed onset muscle soreness (DOMS), torque, and accumulation of technetium-99m (Tc-99m) neutrophils in eccentric-exercised muscle. A group of 10 female and 12 male subjects took part in this study. The subjects completed a pre-test using the descriptor differential scale (DDS) to describe DOMS, and tests of concentric and eccentric torque of the right quadriceps. A volume of 100 ml of blood was taken by venipuncture for neutrophil labelling in the early morning of the exercise day. The Tc-99m neutrophils were re-infused intravenously before the eccentric exercise. The exercise stimulus consisted of 300 eccentric repetitions of the right quadriceps muscles. Radionuclide images of both quadriceps muscles (lateral views) were taken at 2 and 4 h. The DDS, and concentric and eccentric torques of the quadriceps were subsequently evaluated at 0 h, 2, 4, 20 and 24 h post-exercise. The presence of Tc-99m neutrophils was greater in the exercised leg than the non-exercised leg at 2 and 4 h post-exercise (P

Multiple line source array for SPECT transmission scans: simulation, phantom and patient studies.

UNLABELLED: Accurate attenuation and scatter corrections in quantitative SPECT studies require attenuation maps of the density distribution in the scanned object. These can be obtained from simultaneous emission/transmission scans. METHODS: A new method has been developed using a multiple line source array (MLA) for transmission scans, and its performance has been investigated using computer simulations and experimental data. The activity in the central lines of the MLA was higher than at the edges of the system, so that more transmission photons would be directed toward the thicker parts of the human body. A series of transmission-only and simultaneous emission/transmission studies were performed for different phantom configurations and human subjects. Attenuation maps were generated and used in reconstruction of attenuation-corrected emission images. RESULTS: The mu coefficients for attenuation maps obtained using the MLA system and simulated and experimental data display no artifacts and are qualitatively and quantitatively correct. For phantoms, the agreement between the measured and the true value of mu for water was found to be better than 4%. The attenuation-corrected emission images for the phantom studies demonstrate that the activity in the heart can be accurately reconstructed. A significant qualitative improvement was also obtained when the attenuation correction was used on patient data. CONCLUSION: Our results indicate that the MLA transmission source can be used in simultaneous transmission/emission imaging to generate accurate attenuation maps. These maps allow for performing an object-specific, attenuation correction of the emission images.

Kinetic analysis and comparison of uptake, distribution, and excretion of 48V-labeled compounds in rats.

Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48V-BMOV compared with 48VS. The highest 48V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48V was eliminated unabsorbed by fecal excretion. On average, 48V concentrations in bone, kidney, and liver 24 h after oral administration of 48V-BMOV were two to three times higher than those of 48VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.

Interstitial lymphoscintigraphy for lymphatic mapping in surgical practice and research.

Lymphoscintigraphy is a nuclear medicine technique that gives morphologic and functional information about the lymphatic system. The size of radiopharmaceutical used is a critical factor for it to have acceptable characteristics of uptake by the lymphatics and migration to lymph nodes. A small particle (10-100 nm) with opsonins or a unique surface is required for uptake by lymph-node macrophages. It can be prepared for application with a simple filtering process producing a predictable size distribution and number of particles for the scan. The radiation dose is safe for the patient and staff. Technetium-99m sulfur colloid is readily available and approved for use. The injection can be performed by anyone with certification in handling radiopharmaceuticals. Imaging is done with standard gamma cameras available in any nuclear medicine department. The addition of the hand-held gamma probe adds a new dimension to application of the technique of lymphatic mapping and identification of areas that retain radiopharmaceuticals. Its use is simple and reproducible. The application of lymphoscintigraphy and gamma-probe localization techniques in clinical medicine is best exemplified with the now commonly used sentinel node approach to staging and treating intermediate-thickness malignant melanoma. A number of other malignant diseases such as breast cancer may have their treatments altered with these techniques as well. As a research and diagnostic tool, the creative application of interstitial lymphoscintigraphy can give important qualitative information regarding the morphology and physiology of the lymphatic system. The development of these techniques for surgical research and practice is reviewed.

Synthesis and radioiodination of a stannyl oligodeoxyribonucleotide.

Synthesis and radioiodination of a stannyl oligodeoxyribonucleotide were undertaken to evaluate a gamma ray emitting ODN ligand for thrombus imaging in vivo . Synthesis of the ODN was based on modified automatedbeta-cyanoethyl phosphoramidite chemistry with an organotin nucleoside (dU*) coupled to a thrombin binding aptamer sequence to give d(U*GGTTGGTGTGGTTGG). The synthesis accommodated dU*, which is destannylated by iodine or acids. Fourteen standard synthesis cycles were followed by one 'stannyl synthesis cycle', distinguished by Fmoc protection, omission of capping, oxidation by an organic peroxide and cleavage by ammonium hydroxide. The organotin nucleoside phosphoramidite {5'-[fluorenylmethoxycarbonyl]-5-(E)-[2-tri-n -butylstannylvinyl]-2'-deoxyuridine-3'-(2-cyanoethyl N,N-diisopropyl phosphoramidite)} was prepared from 5-iodo-2'-deoxyuridine. A customized mild rapid workup included deprotection with methylamine, and reverse phase HPLC with CH3CN/triethylammonium bicarbonate. Pure stannyl ODN was highly retained by reverse phase HPLC. Radioiodination of stannyl ODN (100 microg) provided 123I-labeling yields up to 97%. Five alternative oxidants were effective. High specific activity [123I]- ODN (15 000 Ci/mmol) was recovered, separated from unlabeled isomers. Excellent reverse phase HPLC resolution of ODN isomers (alternatively I, Cl, H or Br in vinyl deoxyuridine) was essential. The affinity of the iodovinyl aptamer analog (Kd = 36 nM) for human alpha-thrombin was similar to the native aptamer (Kd = 45 nM).

Colonic migrating motor complexes (CMMCs) in the isolated mouse colon.

Spontaneous contractions were recorded from the circular muscle layer at three sites along the isolated mouse colon. The interval between contractions was approximately 4.5 min. The mean duration of the contractions ranged from 26 sec in the distal colon to 45 sec in the proximal colon. Contractions migrating more than half the length of the colon were termed colonic migrating motor complexes (CMMCs). Over 90% of tissues demonstrated migration predominantly in an aboral direction. Hyoscine (10(-6) M) decreased the amplitude of the CMMCs by at least 40% but had no significant effect on the interval or duration of the CMMCs. Nifedipine (10(-6) M) significantly decreased the amplitude of the CMMCs by 95% but did not alter the duration or the interval between the CMMCs. Hexamethonium (5 x 10(-4) M) and tetrodotoxin (TTX; 2 x 10(-6) M) abolished all CMMC activity. TTX increased the resting tone of the preparations. Nitro-L-arginine (10(-4) M) increased the resting tone of the preparations and significantly decreased the interval between the CMMCs by approximately 80% but had no significant effect on the duration of the CMMCs. The results suggest CMMCs migrate predominantly in an aboral direction and are neurogenic in origin. Nitric oxide may be involved in maintaining inhibition of the muscle between CMMCs.

Pulmonary nodules: differential diagnosis using 18F-fluorodeoxyglucose single-photon emission computed tomography.

OBJECTIVE: The objective of this study was to prospectively evaluate the feasibility and efficacy of single-photon emission computed tomography (SPECT) with 18F-fluorodeoxyglucose (FDG) for differentiating malignant from benign pulmonary nodules. SUBJECTS AND METHODS: Twenty-six patients with 28 radiologically indeterminate focal pulmonary lesions were examined. Fasting patients were injected with 5 MBq/kg of FDG (maximum dose, 370 MBq). Imaging was performed with dual-head SPECT cameras equipped with 511-keV collimators. RESULTS: Seventeen of 21 pathologically malignant nodules showed FDG uptake on SPECT imaging (sensitivity, 81%). None of the seven benign modules showed uptake (specificity, 100%). SPECT imaging with FDG was positive in all 16 malignant nodules that were larger than or equal to 2 cm in diameter. However, only one (20%) of five nodules smaller than 2 cm in diameter showed positive on SPECT imaging. CONCLUSION: Using current technology, we found FDG SPECT imaging useful for distinguishing benign from malignant pulmonary nodules that were larger than or equal to 2 cm in diameter. However, because of the relatively low sensitivity of SPECT, smaller malignant nodules were not adequately revealed.

Animal model for investigation of spinal cord injury caused by aortic cross-clamping.

The objective of this experimental protocol was to design a large animal model that could simulate the ischemic condition caused by aortic cross-clamping during the operation for intrathoracic and thoraco-abdominal aneurysm. Domestic swine weighing 25 to 30 kg were used for this model. The thoracic cavity was opened through the fourth intercostal space. Cross-clamp was applied below the left subclavian artery. Duration of cross-clamp was 30 min and the reperfusion period was 24 h. Methods of assessment included Tarlov's criteria, histology transmission electron microscopy, and spinal cord perfusion with microspheres. This model is reproducible. The results of experimental protocols completed using this model are referenced. This article discusses the details of the experimental protocol with steps toward reproduction of the model and rationalization. This animal model can be used for the evaluation of the pathophysiology of spinal cord injury and sensory- and motor-evoked potentials, and most importantly it can also be used for the examination of pharmacological interventions for prevention and treatment of ischemia reperfusion injury caused by aortic cross-clamping.

Presence of WBC, decreased strength, and delayed soreness in muscle after eccentric exercise.

The purposes of this study were to assess the presence of 99mTc-labeled white blood cells (WBC) in exercised muscle compared with nonexercised muscle over time and to determine the time course of delayed onset muscle soreness (DOMS) and eccentric torque in 10 female subjects. A pretest was followed by 300 eccentric repetitions of the right quadriceps. DOMS and eccentric torque were measured at 2, 4, 20, 24, 48, and 72 h postexercise. Eccentric torque was also tested at 0 h. Radionuclide images of both quadriceps were taken at 2, 4, 20, and 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle was significantly greater (P < 0.001) than in the nonexercised muscle. Eccentric torque declined at 0 and 24 h postexercise. DOMS peaked at 24 h postexercise. The presence of 99mTc-WBC in the exercised muscle in the first 24 h suggests that acute inflammation occurs as a result of exercise-induced muscle injury. The bimodal pattern of eccentric torque supports the hypothesis that more than one mechanism is involved.

Electrophysiological analysis of the actions of pituitary adenylyl cyclase activating peptide in the taenia of the guinea-pig caecum.

The actions of pituitary adenylyl cyclase activating peptide (PACAP) on membrane potential and conductance were investigated in the taenia of the guinea-pig caecum. The possible role of PACAP in inhibitory transmission was also investigated. Membrane potentials of smooth muscle cells were measured by intracellular microelectrodes, in the presence of hyoscine and nifidepine (both 10(-6)M. To determine conductance changes, current was passed from external plate electrodes using the technique of Abe and Tomita (1968). PACAP-27 caused a concentration dependent hyperpolarization of the muscle with a maximum of 12-15 mV at 10(-6)M. The hyperpolarization caused by PACAP was associated with a substantial increase in membrane conductance. The hyperpolarization was abolished by apamin (10(-6)M), a blocker of small conductance, calcium-dependent, potassium channels, and was reduced to about 50% by suramin (10(-4)M), which is an antagonist of P2 receptors for purines. The hyperpolarization was not reduced by tetrodotoxin (2 x 10(-6)M), suggesting PACAP acts directly on the muscle. With continued exposure to PACAP, the hyperpolarization decayed back to resting membrane potential after several minutes, possibly due to receptor desensitization. Inhibitory junction potentials (IJPs) were markedly reduced in amplitude in the period of presumed receptor desensitization to PACAP, were abolished by tetrodotoxin, but were not affected by suramin. Apamin abolished the IJP and revealed a small excitatory junction potential. This study implies that PACAP released from nerve fibres in the taenia caeci hyperpolarizes the muscle via an opening of apamin-sensitive potassium channels. The action is probably through type I PACAP receptors.

Contractile activation and measurements of intracellular Ca2+ concentration in cane toad twitch fibres in the presence of 2,3-butanedione monoxime.

The effects of 2,3-butanedione monoxime (BDM, 0.5-20 mM) on Ca(2+)-activated force in skinned muscle fibres, and force and Ca2+ responses in aequorin-injected intact fibres from the iliofibularis muscle of the cane toad Bufo marinus were investigated. Peak twitch force responses progressively decreased to 3% of the control response with increasing [BDM] up to 20 mM. Peak twitch aequorin light responses decreased to 65% of the control response in 10 mM BDM, but increased again to control values in 20 mM BDM. The duration of the twitch aequorin light response increased by up to 60% above 5 mM BDM. Tetanic (170 Hz) force and aequorin light responses reversibly decreased in a dose-dependent fashion to about 50% of the control response in 10 mM BDM. Failure of tetanic (170 Hz) stimulation was observed in the presence of 20 mM BDM. Intracellular [Ca2+] could be modified by changing the frequency of tetanic stimulation in the presence of BDM, permitting a study of the dependence of isometric force on intracellular [Ca2+] at different concentrations of BDM. In 10 mM BDM, the rate of force development in intact fibres was slower by a factor of two at saturating [Ca2+], and was up to one order of magnitude slower at non-saturating [Ca2+], when compared with control responses. At a similar intracellular [Ca2+] steady-state isometric force was reduced to about 85 and 50% of the control responses in 2 and 10 mM BDM, respectively. The effect of BDM on maximum Ca2+-activated force in skinned fibres paralleled the decrease in tetanic (170 Hz) force observed in intact fibres. The rate of force development in skinned fibres decreased with an increase in [BDM] at constant [Ca2+], and the sensitivity of the contractile apparatus to Ca2+ was shifted to a higher [Ca2+] by BDM. The results suggest that BDM reduces contractility in cane toad iliofibularis muscle by direct inhibition of the contractile apparatus, and reduction of the release of activator Ca2+ from the sarcoplasmic reticulum. Furthermore, BDM may be a useful tool to help study the relationship between force and [Ca2+] in intact muscle fibres.

Neurogenic control of myoelectric complexes in the mouse isolated colon.

BACKGROUND/AIMS: Little is known about the mechanisms controlling colonic migrating electrical activity. This study investigates the neural processes involved in the generation of migrating myoelectric complexes in the isolated mouse colon. METHODS: Intracellular electrophysiological recordings were obtained from the circular muscle layer of the mouse colon in vitro in the presence of 2 mumol/L nifedipine. RESULTS: Complexes occurred approximately every 3 minutes and consisted of 1 mumol/L hyoscine-sensitive rapid oscillations (approximately 2 Hz) superimposed on a slow depolarization (approximately 17 mV); the latter was often preceded by a precomplex hyperpolarization (approximately 7 mV) that was reduced by 250 nmol/L apamin. Five hundred micromolars of hexamethonium or 2 mumol/L of tetrodotoxin abolished the complexes and depolarized the muscle by 8.7 +/- 1.3 mV (n = 9) or 12.1 +/- 1.4 mV (n = 5), respectively. Carbachol (50 nmol/L to 5 mumol/L) produced dose-dependent depolarizations but without rapid oscillations. The nitric oxide synthase inhibitor NG-nitro-L-arginine (100 mumol/L) depolarized the tissue by 17.2 +/- 1.6 mV (n = 8) but had no effect on the rapid oscillations. In the presence of 2 mumol/L tetrodotoxin, 5 mumol/L sodium nitroprusside produced a sustained hyperpolarization (15.5 +/- 2.0 mV; n = 5) but did not restore complexes. CONCLUSIONS: In the isolated mouse colon, the membrane potential between complexes is maintained by the release of inhibitory neurotransmitters (including nitric oxide), and the formation of complexes involves disinhibition and the simultaneous activation of cholinergic motor nerves.

No-carrier-added [123I]1-(beta-D-arabinofuranosyl)-5(E)-(2- iodovinyl)uracil (IVaraU): high yield radiolabeling via organotin and exchange reactions.

Organotin intermediates for IVaraU synthesis were obtained following the reaction of 1-(2',3',5'-tri-O-toluyl-beta-D-arabinofuranosyl-5-iodouracil with (E)-1,2-bis(tri-(n-butyl) stannyl)ethene in the presence of catalytic (Ph3P)2PdCl2. A direct precursor for IVaraU, (E)-5-[2-tri-n-butylstannylvinyl]-arabinosyluridine, reacted with [123I]NaI (10 mCi) or alternatively [125I]NaI in the presence of methanol and chloramine T providing no-carrier-added (NCA) [123I]IVaraU in a radiolabeling yield up to 97%; the product was recovered following reversed phase HPLC. Unlabeled IVaraU was prepared in five steps from arabinosyluridine via an organotin intermediate with an overall yield of 22%. An exchange radioiodination was also identified, based on accessible BrVara U in the presence of water and a cuprous ion catalyst. [123I]NaI (up to 40 mCi) or alternatively [125I]NaI reacted under exchange conditions to give no-carrier-added [123,125I]IVaraU in a radiolabeling yield of 93%; the product was recovered following reversed phase HPLC.

Additive effect of allopurinol and deferoxamine in the prevention of spinal cord injury caused by aortic crossclamping.

Fourteen domestic swine were divided into two groups. Group A (n = 7) was the control group, in which no pharmacologic intervention was applied. In group B (n = 7), the ischemic-reperfused spinal cord was treated with the combination of allopurinol (50 mg/kg/day for 3 days before the day of operation) and deferoxamine (Desferal, 50 mg/kg administered intravenously over 3 to 4 hours). The administration of deferoxamine was completed 1 hour before crossclamping. The crossclamp was placed on the descending aorta just distal to the left subclavian artery for 30 minutes. Proximal hypertension was controlled with sodium nitroprusside and volume depletion. Methods of assessment included an evaluation of the neurologic status of the animals by quantitative Tarlov criteria, blood flow by radiolabeled microspheres, and histologic examination of the spinal cord. All animals in the control group, group A, were completely paraplegic with 0% recovery by Tarlov criteria at 24 hours after the removal of the crossclamp. In contrast, all animals in group B, in which the combination of allopurinol and deferoxamine was used, completely recovered (100% recovery by Tarlov criteria), and at 24 hours after the ischemic episode they were able to walk with no difficulty and had intact sensation. Functional parameters of these animals fully correlated with the morphologic findings. Widespread acute neuronal injury and vacuolation of neuropil were observed in the control group of animals. In contrast, animals in group B showed much less pronounced morphologic changes after the same period of ischemia. In summary, the combined use of these agents significantly (p < 0.001) reduced the incidence of paraplegia induced by aortic crossclamping with 82% additivity.

Potential 99mTc radiopharmaceuticals for renal imaging: tris(N-substituted-3-hydroxy-2-methyl-4-pyridinonato)technetium(IV) cations.

A series of monocationic complexes of N-substituted-3-hydroxy-2-methyl-4-pyridinones labeled with technetium(IV)-99m have been evaluated in vivo as potential radiopharmaceuticals. The pyridinones have different substituents at the ring nitrogen atom: ethyl, i-propyl, i-butyl, benzyl, phenyl, p-methoxyphenyl, 3-butoxypropyl and cyclohexyl. Biodistribution studies of the 99mTc complexes have been carried out in rabbits and mice. High kidney uptake and retention of the radionuclide has been shown in rabbits and mice with the cationic complexes of 3-hydroxy-1-(p-methoxyphenyl)-2-methyl-4-pyridinone and 1-(cyclohexyl)-3-hydroxy-2-methyl-4-pyridinone. These 99mTcL3+ compounds appear to be morphologic renal agents.