Deblurring subject to nonnegativity constraints when known functions are present with application to object-constrained computerized tomography.

The reconstruction of tomographic images is often treated as a linear deblurring problem. When a high-density, man-made metal object is present somewhere in the image field, it is a deblurring problem in which the unknown function has a component that is known except for some location and orientation parameters. We first address general linear deblurring problems in which a known function having unknown parameters is present. We then show how the resulting iterative solution can be applied to tomographic imaging in the presence of man-made foreign objects, and we apply the result, in particular, to X-ray computed tomography imaging used in support of brachytherapy treatment of advanced cervical cancer.

Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Effect of aging on the negative chronotropic and anti-beta-adrenergic actions of adenosine in the rat heart.

The effect of aging on the antiadrenergic actions of adenosine was studied in vitro and in vivo by using adult (6-month-old) and old (24-month-old) male Fischer 344 rats. In anesthetized animals, adenosine (0.01-0.1 micromol/kg), given as a rapid bolus into the right atrium, exerted a negative chronotropic effect manifested by a dose-dependent transient prolongation of sinus cycle length (SCL). This effect was similar in both age groups (n = 6, each; i.e., the percentage maximal prolongation of SCL (%deltaSCL) ranged from 12 +/- 2% to 63 +/-14% in the adult and from 20 +/- 7% to 57 +/- 15% in the old rats. In the presence of isoproterenol (0.2 microg/kg/min), the negative chronotropic action of adenosine was potentiated in the adult rats much more than in the old rats [i.e., %deltaSCL ranged from 60 +/- 28% to 183 +/- 48% vs. 40 +/- 12% to 70 +/- 13%, respectively (p < 0.05, adult vs. old)]. In the isolated perfused hearts, isoproterenol (1 microM for 1 min) exerted similar chronotropic and inotropic effects in adult (n = 9) and old hearts [n = 6; i.e., heart rate, left ventricular pressure (LVP), and LVdp/dt increased by 56 +/- 3%, 17 +/- 1%, and 37 +/- 2%, and 57 +/- 2%, 17 +/- 1%, and 35 +/- 3%, respectively, in the absence of, and by 27 +/- 2%, 7 +/- 1%, and 19 +/- 2% and 41 +/- 3%, 12 +/- 1%, and 25 +/-2% in the presence of adenosine (5 microM for 1 min)]. Adenosine administration after isoproterenol caused only an insignificant increase in coronary blood flow. Finally, the adenosine attenuation of either isoproterenol- or forskolin-induced production of 3',5'-cyclic adenosine monophosphate (cAMP) was significantly less in atrial membranes isolated from old versus adult rats (n = 6, each). It was concluded that in the old Fischer 344 rat hearts, the antiadrenergic action of adenosine is attenuated as compared with its action in adult rat hearts.

Theoretical development and experimental evaluation of imaging models for differential-interference-contrast microscopy.

Imaging models for differential-interference-contrast (DIC) microscopy are presented. Two- and three-dimensional models for DIC imaging under partially coherent illumination were derived and tested by using phantom specimens viewed with several conventional DIC microscopes and quasi-monochromatic light. DIC images recorded with a CCD camera were compared with model predictions that were generated by using theoretical point-spread functions, computer-generated phantoms, and estimated imaging parameters such as bias and shear. Results show quantitative and qualitative agreement between model and data for several imaging conditions.

Cardiovascular effects of acute and chronic cocaine administration in pregnant and nonpregnant rabbits.

The effects of cocaine administration on cardiovascular parameters were studied in anesthetized nonpregnant and pregnant rabbits with no prior exposure to cocaine and in pregnant rabbits repeatedly administered cocaine (4 mg/kg, bid, iv) for 15-20 days prior to the experiment. Rabbits were instrumented to determine the effects of cocaine on blood pressure, heart rate, and organ blood flows. Administration of the 1 and 2 mg/kg doses of cocaine increased blood pressure and decreased heart rate in both pregnant and nonpregnant rabbits. In contrast, the 4 mg/kg dose of cocaine caused reductions in both blood pressure and heart rate. Cocaine (1, 2, and 4 mg/kg, iv) also caused dose-dependent reductions in organ blood flows. Interestingly, cocaine did not affect uterine blood flow in the nonpregnant rabbits, whereas uterine and placental flows were markedly reduced in both groups of pregnant rabbits. Chronic treatment with cocaine caused a significant increase in the basal blood flow to the placenta and spleen, and a more precipitous decrease in blood flow in both organs in response to an acute injection of cocaine. The chronically treated rabbits also had a greater incidence of cardiac arrhythmias in response to an acute injection of cocaine (4 mg/kg, iv). Rabbits that received repeated administrations of cocaine experienced more prolonged reductions in blood flow than rabbits with no prior exposure to cocaine. These studies show that cocaine has marked effects on organ blood flows and that pregnancy and repeated prior administrations of cocaine can enhance these effects.

Developmental toxicity interactions of salicylic acid and radiofrequency radiation or 2-methoxyethanol in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces where workers are concurrently exposed to chemicals. Combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research was to determine if the synergistic effects noted for RF radiation and 2ME are generalizable to other chemicals. Since salicylic acid (SA) is widely used as an analgesic and is teratogenic in animals, SA was selected to address generalizability. Based on the literature and our pilot studies, 0, 250, or 350 mg/kg SA were administered by gavage on gestation Day 9 or 13 to rats. Concurrently rats given SA on Day 9 were exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 min (or sham). Those given SA on Day 13 were also given 0 or 100 mg/kg 2ME (gavage). Dams were sacrificed on gestation Day 20, and the fetuses were examined for external malformations. The data provide no evidence of synergistic interactions between RF radiation and salicylic acid (resorptions and malformations). Limited evidence of antagonism was observed between 2ME and salicylic acid (fetal weights). This investigation highlights the importance of additional research on interactions in developmental toxicology, and emphasizes the need to consider combined exposure effects when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Influence of age and dietary restriction on norepinephrine uptake into cardiac synaptosomes.

The purpose of this study was to determine whether aging alters neuronal uptake of norepinephrine (NE) in the rat heart and if dietary restriction influenced the effect of age on this system. Cardiac synaptosomes were prepared from 6-, 12- and 24-month-old male F344 rats fed ad libitum (AL) or a diet restricted (DR) to 60% of AL intake. Cardiac synaptosomes were incubated with 50, 100, 200, or 400 nM [3H]NE for 10 min at 37 degrees C with and without desmethylimipramine (DMI), a selective neuronal-uptake blocker. DMI-sensitive [3H]NE uptake was calculated as the difference between samples with and without DMI. NE uptake was adjusted for the number of cardiac synaptosomes in each sample by dividing by the endogenous NE content in each sample. The Vmax for uptake ([3H]NE/min/ng NE) declined significantly between 6 and 12 months in AL rats and between 12 and 24 months in DR rats. Km was not significantly different between age or diet groups. The change in Vmax with age suggests that the number of NE transporters per synaptosome may decline with age and that DR delays this effect of age. There were no differences in the sensitivity to DMI between age or diet groups.

Effect of environmental temperature on the interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats.

OBJECTIVE: This research was conducted to determine if altered environmental temperatures would affect the interactive developmental toxicity of radiofrequency (RF) radiation and the industrial solvent, 2-methoxyethanol (2ME). This is important because RF radiation is used in a variety of workplaces that have poorly controlled environmental temperatures, and many workers are concurrently exposed to various chemicals. Furthermore, we have previously demonstrated that combined exposure to RF radiation (10 MHz) and 2ME produces enhanced teratogenicity in rats. METHODS: RF radiation sufficient to maintain colonic temperatures at the control value (38degrees ), 39.0degrees or 40.0 degrees C for 2 or 4 h combined with either 0 or 100 mg/ kg 2ME at environmental temperatures of 18 degrees , 24 degrees and 30 degrees C (65 degrees , 75 degrees , and 85 degrees F) were given on gestation day 13 to Sprague-Dawley rats. Dams were killed on gestation day 20, and the fetuses were examined for external malformations. RESULTS AND CONCLUSIONS: Environmental temperature does affect the specific absorption rate (SAR) necessary to maintain a specific colonic temperature but does not affect the interactive developmental toxicity of RF radiation and 2ME in rats. These results, consistent with the literature, add to the evidence that the developmental toxicity of RF radiation (combined or alone) is associated with colonic temperature, not with SAR.

Age-related decline in beta adrenergic and adenosine A1 receptor function in the heart are attenuated by dietary restriction.

Previously published reports from this laboratory have shown that the antiadrenergic effect of adenosine A1 agonists declines with age in the rat heart [ J Mol Cell Cardiol 29:593-602] and that this decline may be caused by a decrease in coupling between adenosine A1 receptors (AdoA1R) and guanine nucleotide-binding proteins [ Circ Res 81:1065-1071]. Dietary restriction (DR; 60% calories of ad libitum) has been shown to attenuate age-related changes in cellular signal transduction pathways. Therefore, the present study investigated whether DR altered the age-related changes in AdoA1R-mediated function in senescent rat hearts. Ventricular membranes were isolated from the hearts of ad libitum (AL) fed and DR male F344 rats that were 6, 12 and 24 months of age. In AL rats, there was an age-related decline in isoproterenol (ISO)-stimulated adenylyl cyclase when compared with the 6-month-old rats. The decline in ISO-stimulated cyclase was attenuated in DR animals. In AL rats, inhibition of ISO-stimulated adenylyl cyclase by the AdoA1R agonist, N6-p-sulfophenyladenosine (SPA) decreased with age. In DR rats, the age-related decline in inhibition was attenuated. Previous results from this laboratory indicated that in AL fed rats, there was an age-related decrease in the percentage of high-affinity binding sites for SPA, from 55% at 6 months to 23% at 24 months. Diet restriction attenuated this age-related shift in high-affinity binding sites so that the percentage of high-affinity sites at 24 months was 42%. Our results suggest that DR maintains AdoA1R function by preventing a loss of high-affinity AdoA1R sites.

Effect of aging on A1-adenosine receptor-mediated inhibition of norepinephrine release in the rat heart.

Adenosine inhibits norepinephrine (NE) release from cardiac adrenergic nerves and reduces the postsynaptic beta-adrenergic mediated actions of NE, leading to decreased myocardial force of contraction. The actions of adenosine are mediated by pre- and postsynaptic adenosine A1 receptors (A1-AdoR). We reported that adenosine inhibition of postsynaptic beta-adrenergic receptor-mediated cyclic adenosine monophosphate (cAMP) production declines with age in male F344 rat hearts. In this study, cardiac synaptosomes, isolated intact adrenergic nerve terminals, were used to examine the effect of age on adenosine inhibition of NE release. Cardiac synaptosomes were prepared from the hearts of 6- and 24-month-old male F344 rats, loaded with [3H]NE, and placed in a superfusion system. [3H]NE release was induced by high [K+] exposure in the presence of varying concentrations of adenosine or the specific A1-AdoR agonist, N6-p-sulfophenyladenosine (SPA). [3H]NE release was significantly reduced in old rats compared with young rats. Inhibition of [3H]NE release by adenosine and SPA was significantly greater in young rats compared with old rats. The A1-AdoR antagonist, 8-(p-sulfophenyl)-theophylline, blocked the actions of adenosine on [3H]NE release, and the specific adenosine A2-receptor agonist, cyclopropylcarboxamidoadenosine, had no effect on [3H]NE release. Our data suggest that presynaptic A1-AdoR-mediated inhibition of NE release in the rat heart declines with age.

Effect of age, gender, rat strain, and dietary restriction, on norepinephrine release from cardiac synaptosomes.

The purpose of the present study was to determine if dietary restriction affected NE release from cardiac synaptosomes obtained from old male F344 rats. Female F344 rats and male and female B/N rats were also examined to determine if age-related changes in norepinephrine (NE) release capacity in the heart are strain- and/or gender-specific. F344 and Brown-Norway (B/N) rats were examined at 6, 12, and 24 months; B/N rats were also examined at 28-30 months. K(+)-induced NE release significantly declined with age in male F344 and B/N rats; this decline was attenuated in female rats and in dietary restricted rats, especially at 24 months. The present study demonstrates that aging reduces the capacity of cardiac adrenergic nerve terminals to release NE, this age-related change is not strain specific, and that dietary restriction and gender alter the extent of this change with age.

Reduced adenosine A1 receptor and G alpha protein coupling in rat ventricular myocardium during aging.

Adenosine A1 receptor (A1-AdoR) function in rat ventricles has previously been shown to decrease with age. In the present study, using the ligand [3H]8-cyclopentyl-1,3-dipropylxanthine ([3H]DPCPX) and coimmunoprecipitation of A1-AdoRs with their associated G proteins, we determined the specific binding of A1-AdoR and A1-AdoR/G protein coupling in ventricular myocardium of 6- to 24-month-old Fischer 344 rats. The densities (Bmax) of A1-AdoRs were 5.8 +/- 0.8 fmol/mg protein in 6-month-old rats and 6.1 +/- 1.4 fmol/mg protein in 24-month-old rats, and the dissociation constants (Kd) were 0.32 +/- 0.04 nmol/L in 6-month-old rats and 0.34 +/- 0.05 nmol/L in 24-month-old rats (P > .05). Analysis of the dose-dependent displacement of [3H]DPCPX binding by the selective A1-receptor agonist, N6-p-sulfophenyladenosine (SPA), yielded two affinity binding sites in both 6- and 24-month-old rats. However, the proportion of high-affinity A1-AdoRs was significantly lower in 24-month-old rats (23.5%) compared with 6-month-old rats (54.9%) (P < .05). In solubilized ventricular membranes, specific [3H]DPCPX binding sites were detected in immunoprecipitates of G alpha i3 and G alpha o antisera but not with antibodies for other G alpha proteins. The basal coimmunoprecipitation of A1-AdoR with G alpha i3 and G alpha o proteins decreased by 22% and 21%, respectively, in ventricular membranes of 24-month-old rats compared with that in 6-month-old animals. A1-AdoR stimulation with SPA increased the coprecipitation of A1-AdoR with G alpha i3 and G alpha o proteins by 287% and 245%, respectively, in 6-month-old rats but only by 129% and 140%, respectively, in 24-month-old rats (P < .01). In the absence of changes in A1-AdoR density and G alpha protein levels, an age-related decline in high-affinity A1-AdoR binding sites and a reduction in the association of A1-AdoR with G alpha proteins suggest that the age-related decrease in ventricular A1-AdoR-mediated response is related to a reduction in the coupling between A1-AdoR and their G proteins.

The effect of age on adenosine A1 receptor function in the rat heart.

Adenosine is an important regulatory metabolite in the heart where it has a cardioprotective function. In the ventricle, the cardioprotective action of adenosine is mediated through the adenosine A1 receptor and inhibition of adenylyl cyclase. In order to investigate the effect of age on adenosine signal transduction in the heart, the effect of specific adenosine A receptor agonists on adenylyl cyclase activity was measured in crude cardiac ventricular membranes isolated from 1-, 6- and 24-month-old Fisher 344 rats. There were no differences in basal cyclase activity with age. Consistent with observations from other laboratories, isoproterenol- and forskolin-stimulated cyclase activity decreased with age. In addition, there was an age-related decline in the capacity of adenosine to inhibit stimulated adenylyl cyclase. The specific A1 adenosine receptor agonists, N6-cyclopentyladenosine (CPA) and N6-p-sulfophenuladenosine (SPA) inhibited isoproterenol- and forskolin-stimulated adenylyl cyclase activity in cardiac membranes from 1-month and 6-month-old rats; however, CPA and SPA did not inhibit adenylyl cyclase in membranes from 24-month-old rats. These data indicate that in addition to the age-related decline in beta-adrenergic receptor function with age, there is also a decrease in adenosine A; receptor-mediated responses. In contrast, carbachol acting through muscarinic receptors, caused the same inhibition of adenylyl cyclase at all ages. Therefore, the age-related decline in inhibitory signal transduction is specific to the adenosine A1 receptor. The age-related defect is probably at the level of the adenosine/receptor interaction and/or the receptor/guanine nucleotide binding protein interaction.

Interactions of radiofrequency radiation on 2-methoxyethanol teratogenicity in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with microelectronics industry, plastic sealers and electrosurgical units. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to radiofrequency (r.f.; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent 2-methoxyethanol (2ME) produces enhanced teratogenicity in rats. A subsequent study replicated and extended that research by investigating the interactive dose-related teratogenicity of r.f. radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20 or 30 min by r.f. radiation absorption) and 2ME (0, 75, 100, 125 or 150 mg/kg) on gestation days 9 or 13 of rats. The purpose of the present research is to determine the effects of r.f. radiation (sufficient to maintain colonic temperatures at 42.0 degrees C for 10 min) on a range of doses of 2ME (0, 20, 40, 60, 80, 100, 120 and 140 mg kg-1) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Dose-related developmental toxicity was observed for 2ME both in the presence and absence of r.f. radiation. However, concurrent RF radiation exposure changed the shape of the dose-effect curve of 2ME. These data indicate that combined exposure effects should be considered when developing exposure guidelines and intervention strategies.

Interactions of radiofrequency radiation-induced hyperthermia and 2-methoxyethanol teratogenicity in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces. In addition to RF radiation, many workers are concurrently exposed to numerous chemicals; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research is to determine the effects of varying the degree and duration of hyperthermia induced by RF radiation (sufficient to maintain colonic temperatures at control [38.5], 39.0, 40.0, or 41.0 degrees C for up to 6 h) and 2ME (100 mg/kg) administered on gestation day 13 of rats. Focusing on characterizing the dose-response pattern of interactions, this research seeks to determine the lowest interactive effect level. Day 20 fetuses were examined for external and skeletal malformations. The results are consistent with previous observations. Significant interactions were observed between 2ME and RF radiation sufficient to maintain colonic temperatures at 41 degrees C for 1 h, but no consistent interactions were seen at lower temperatures even with longer durations. These data indicate that combined exposure effects should be considered when developing both RF radiation and chemical exposure guidelines and intervention strategies.

Automatic target recognition organized via jump-diffusion algorithms.

Proposes a framework for simultaneous detection, tracking, and recognition of objects via data fused from multiple sensors. Complex dynamic scenes are represented via the concatenation of simple rigid templates. The variability of the infinity of pose is accommodated via the actions of matrix Lie groups extending the templates to individual instances. The variability of target number and target identity is accommodated via the representation of scenes as unions of templates of varying types, with the associated group transformations of varying dimension. We focus on recognition in the air-to-ground and ground-to-air scenarios. The remote sensing data is organized around both the coarse scale associated with detection as provided by tracking and range radars, along with the fine scale associated with pose and identity supported by high-resolution optical, forward looking infrared and delay-Doppler radar imagers. A Bayesian approach is adopted in which prior distributions on target scenarios are constructed via dynamical models of the targets of interest. These are combined with physics-based sensor models which define conditional likelihoods for the coarse/fine scale sensor data given the underlying scene. Inference via the Bayes posterior is organized around a random sampling algorithm based on jump-diffusion processes. New objects are detected and object identities are recognized through discrete jump moves through parameter space, the algorithm exploring scenes of varying complexity as it proceeds. Between jumps, the scale and rotation group transformations are generated via continuous diffusions in order to smoothly deform templates into individual instances of objects.

Local computed tomography via iterative deblurring.

X-ray computed tomography is a major imaging modality. An iterative deblurring method is adapted for local reconstruction in parallel-beam and cone-beam geometries, utilizing only x-rays passing through a region of interest. The feasibility is demonstrated in numerical simulation with noise-free and noisy projection data. The iterative deblurring method has the theoretical advantages of maintaining nonnegativity, converging monotonically and minimizing Csiszàr's I-divergence.

Iterative deblurring for CT metal artifact reduction.

Iterative deblurring methods using the expectation maximization (EM) formulation and the algebraic reconstruction technique (ART), respectively, are adapted for metal artifact reduction in medical computed tomography (CT). In experiments with synthetic noise-free and additive noisy projection data of dental phantoms, it is found that both simultaneous iterative algorithms produce superior image quality as compared to filtered backprojection after linearly fitting projection gaps. Furthermore, the EM-type algorithm converges faster than the ART-type algorithm in terms of either the I-divergence or Euclidean distance between ideal and reprojected data in the authors' simulation. Also, for a given iteration number, the EM-type deblurring method produces better image clarity but stronger noise than the ART-type reconstruction. The computational complexity of EM- and ART-based iterative deblurring is essentially the same, dominated by reprojection and backprojection. Relevant practical and theoretical issues are discussed.

Cardiovascular hypertrophy and increased vascular contractile responsiveness following repeated cocaine administration in rabbits.

The effects of repeated cocaine administration on contractile responses were studied in adult rabbits. Repeated cocaine exposure caused a significant increase in the maximal response of the aorta to the agonists norepinephrine and serotonin as well as the receptor- independent stimulus KCl when compared to the saline controls. Cocaine exposure caused a significant increase in the wet weights of both heart and aorta. When the contraction was normalized to the wet weight of the aorta there was no difference between rabbits administered cocaine and saline. Acute cocaine administration caused a time-dependent increase in immunoreactivity of the proto-oncogene c-Fos in the aorta. These results show that repeated cocaine administration leads to the development of cardiovascular hypertrophy.

Age-related changes in cardiac norepinephrine release: role of calcium movement.

The purpose of this study was to determine if the age-related decrease in norepinephrine (NE) release from cardiac adrenergic nerve terminals is due to a defect in Ca2+ movement into the nerve terminal or to an alteration in Ca2+ activation of intracellular events leading to NE release. NE release was assessed in cardiac synaptosomes prepared from 6- and 24-month-old male F344 rats. K(+)-induced NE release was significantly greater in young vs old rats. Raising extracellular [Ca2+] increased NE release, but NE release always remained higher in the younger animals. Ionomycin, a Ca2+ ionophore, induced NE release from cardiac synaptosomes, and there was no age difference in the response. The age-related reduction in NE release induced by K+ and the capacity of ionomycin to induce similar NE release in young and old cardiac synaptosomes points to a reduction in Ca2+ movement during depolarization.