Biomedical subjects

C T Wong

Publications and source records attributed to C T Wong.

At least 19 recordsLinked to original sources

PubMed2005

Vertebroplasty by use of a strontium-containing bioactive bone cement.

STUDY DESIGN: A review of the laboratory and clinical data for a new strontium-containing hydroxyapatite bioactive bone cement. OBJECTIVES: To compare the properties of the strontium-containing bioactive bone cement with those of polymethyl methacrylate (PMMA) and hydroxyapatite (HA) bone cements. SUMMARY OF BACKGROUND DATA: Vertebroplasty and kyphoplasty using conventional PMMA bone cements have been effectively used to treat osteoporotic spine fractures with good short- and medium-term results. However, PMMA has some undesirable properties, including its high setting temperature, lack of osseointegration, and large stiffness mismatch with osteoporotic bone. These properties are responsible for some postoperative complications. METHODS: Strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement consists of a filler blend of strontium-containing hydroxyapatite, fumed silica and benzoyl peroxide; and a resin blend of bisphenol A diglycidylether methacrylate, triethylene glycol dimethacrylate, poly(ethylene glycol) methacrylate, and N, N-dimethyl-p-toluidine. Its properties, including mechanical strength, setting temperature, biocompatibility, and osseoinduction, were compared with other cements in vitro and in vivo. Early clinical results are presented. RESULTS: The Sr-HA cement has a setting time of 15 to 18 minutes, a maximum setting temperature of 58 degrees C, a compressive strength of 40.9 MPa, bending strength of 31.3 MPa, and a bending modulus of 1,408 MPa. The bending strength and modulus are closer to human cancellous bone. Sr-HA cement promotes osteoblast attachment and mineralization in vitro and bone growth and osseointegration in vivo. In a pilot study, 23 cases of osteoporotic fractures treated with this cement with a mean follow-up of 18 months suggest that it is as effective as PMMA in relieving pain. DISCUSSIONS: Oral strontium has been shown to induce new bone formation and is effective in reducing fracture risk in osteoporosis. Our data suggest that strontium delivered locally has the same effect; thus, the combination of strontium with HA in a cement with a low setting temperature, adequate stiffness, and low viscosity makes this a good bioactive cement for vertebroplasty and kyphoplasty.

Animals↗

PubMed2004

Ultrastructural study of mineralization of a strontium-containing hydroxyapatite (Sr-HA) cement in vivo.

The purpose of this study was to investigate the mineralization leading to osseointegration of strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement injected into cancellous bone in vivo. Sr-HA cement was injected into the ilium of rabbits for 1, 3, and 6 months. The bone mineralization area was found to be largest at 3 months, then at 1 month, and smallest at 6 months (p < 0.01) measured with tetracycline labeling. Osseointegration of Sr-HA cement was achieved at 3 months as observed by scanning electron microscopy. A high calcium and phosphorus area was observed at the interface of bone-Sr-HA cement determined by energy-dispersive X-ray analysis. Transmission electron microscopy gave evidence of the mechanism of bone formation. Dissolution of Sr-HA into debris by the bone remodeling process was thought to increase the concentration of calcium and phosphorus at the interface of bone-Sr-HA cement and stimulate bone formation. Crystalline Sr-HA formed an amorphous layer and dissolved into the surrounding solution, then apatite crystallites were precipitated and formed new bone at 3 months. This young bone then becomes mature bone, which bonds tightly to the Sr-HA cement with collagen fibers inserted perpendicularly after 6 months.

Animals↗

PubMed2004

Surface treatment of injectable strontium-containing bioactive bone cement for vertebroplasty.

A novel injectable bioactive bone-bonding cement (SrHAC) composed of strontium-containing hydroxyapatite (Sr-HA) as the inorganic filler and bisphenol A diglycidylether dimethacrylate (Bis-GMA) as the organic matrix for vertebroplasty was developed previously. In this study, the Sr-HA powders were surface treated with methyl methacrylate (MMA) to improve the interface integration of the two phases. After surface treatment, the compression strength and Young's modulus, which were tested after immersion in distilled water at 37 degrees C for 24 h according to ISO 5833, were increased by 68.65 % (p <.001) and 31.02% (p <.001), respectively. The bending strength and bending stiffness of the bioactive bone cement were significantly improved by 54.44% (p <.001) and 83.90% (p <.001). In addition, the handling property of the cement was also enhanced. In vitro biomechanical testing showed that the stiffness of the fractured spine recovered to 82.5% (p <.01) of the intact condition after cementation with surface-treated SrHAC. The failure load of the spine cemented with original and MMA-treated SrHAC improved by 14.25% (p <.05) and 46.91% (p <.05) in comparison with the fractured spines. Results from this study revealed that the MMA-treated SrHAC has a better mechanical effect for orthopedic applications.

Animals↗

PubMed2004

In vivo cancellous bone remodeling on a strontium-containing hydroxyapatite (sr-HA) bioactive cement.

The purpose of this study was to investigate the in vivo bone response to the strontium-containing hydroxyapatite (Sr-HA) bioactive bone cement injected into the cancellous bone. Sr-HA cement was injected into the iliac crest of rabbits for 1, 3, and 6 months. Active bone formation and remodeling were observed after 1 month. Newly formed bone was observed to grow onto the bone cement after 3 months. Thick osteoid layer with osteoblasts formed along the bone and guided over the bone cement surface reflected the stimulating effect of Sr-HA. From scanning electron microscopy (SEM) and energy-dispersive X-ray (EDX) analysis, high calcium and phosphorus levels were detected at the interface with a thick layer of 70 microm in width, and fusion of Sr-HA with the bone was observed. Blood vessels were found developing in remodeling sites. The affinity of bone on Sr-HA cement was increased from 73.55 +/- 3.50% after 3 months up to 85.15 +/- 2.74% after 6 months (p < 0.01). In contrast to Sr-HA cement, poly(methyl methacrylate) (PMMA) bone cement was neither osteoconductive nor bioresorbable. Results show that the Sr-HA cement is biocompatible and osteoconductive, which is suitable for use in treating osteoporotic vertebral fractures.

Animals↗

PubMed2004

Strengthening mechanisms of bone bonding to crystalline hydroxyapatite in vivo.

The formation and strengthening mechanisms of bone bonding of crystalline hydroxyapatite (HA) has been investigated using high-resolution transmission electron microscope (HRTEM) and energy-dispersive X-ray (EDX) analysis. A series of results were obtained: (i) a layer of amorphous HA, which has almost the same chemistry as the implanted HA, was formed on the surface of crystalline HA particles prior to dissolution; (ii) at 3 months a bone-like tissue formed a bonding zone between mature bone and the HA implant, composed of nanocrystalline and amorphous apatite; and (iii) at 6 months, mature bone was in direct contact with HA particles, and collagen fibres were perpendicularly inserted into the surface layer of implanted HA crystals. Findings (i) and (ii) indicated the following dissolution-precipitation process. (i) The crystalline HA transforms into amorphous HA; (ii) the amorphous HA dissolves into the surrounding solution, resulting in over-saturation; and (iii) the nanocrystallites are precipitated from the over-saturated solution in the presence of collagen fibres. A preliminary analysis indicated several conclusions: (i) the transition from crystalline to amorphous HA might be the controlling step in the bone bonding of crystalline HA; (ii) biological interdigitation (or incorporation) of collagen fibres with HA and chemical bonding of a apatite layer were both necessary to strengthen and toughen a bone bond, not only for the bonding between bone and HA at 6 months, but also for the bonding zone at 3 months, which would otherwise be very fragile due to the inherited brittleness of polycrystalline ceramics; and (iii) perpendicular interdigitation is an effective way for collagen fibres to impart their unique combination of flexibility and strength to the interface which they are keying.

Adhesiveness↗

PubMed2001

Brain dopamine and obesity.

BACKGROUND: The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. METHODS: Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG). FINDINGS: Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. INTERPRETATION: The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.

Adult↗

PubMed2000

Increased activity of the temporal insula in subjects with bradycardia.

Though it has been postulated that cortical brain regions participate in the regulation of heart rate, their involvement is poorly understood. Using PET and [18] FDG (to measure regional brain glucose metabolism, which serves as an index of brain function) we compared the regional brain metabolic activity between healthy subjects with bradycardia (<60 beats per minute) with those with normal heart rates in the 75-100 beats per minute range. Statistical Parametric Mapping (SPM) analyses revealed significant differences between the groups predominantly localized to the temporal insula. This finding was corroborated by a separate analysis that measured the metabolic activity for each subject in preselected regions located in the temporal insula. Subjects with bradycardia had significantly higher metabolic activity in the right (p < 0.0001) and in the left temporal insula (p < 0.015) than those with normal heart rates. Moreover, resting heart rates were negatively correlated with metabolism in the right (r = -0.77, p < 0.0001) and in the left temporal insula (r = -0.44, p < 0.05). These results corroborate the importance of the temporal insula in the regulation of resting heart rate in humans. The temporal insula is interconnected with limbic brain region and autonomic centers and suggests that this may be a mechanism by which emotional responses regulate heart rate.

Adult↗

PubMed2000

Regional brain metabolism during alcohol intoxication.

BACKGROUND: Ethanol has a broad range of actions on many neurotransmitter systems. The depressant actions of ethanol in the brain are related in part to facilitation of gamma-aminobutyric acid (GABA) neurotransmission via its interaction with the benzodiazepine/GABA receptor complex. The purpose of this study was to evaluate the effects of ethanol on regional brain metabolism in 10 healthy right-handed men. The results were compared with those we previously published in a different group of 16 normal male subjects who received intravenous lorazepam, a benzodiazepine drug that also enhances GABA neurotransmission. METHODS: The subjects were scanned with positron emission tomography and [F-18] fluorodeoxyglucose twice: 40 min after the end of placebo (diet soda) or ethanol (0.75 g/kg) oral administration. Image data sets were analyzed by using both the region of interest and the statistical parametric mapping (SPM) approach. SPM was used to generate a difference image between baseline and ethanol, which we compared to the difference image between baseline and lorazepam (30 microg/kg). RESULTS: Ethanol significantly increased self-reports of "high" (p < or = 0.0001), dizziness (p < or = 0.004), and intoxication (p < or = 0.0001). Ethanol significantly decreased whole brain (-25 +/- 6%, p < or = 0.0001) and regional metabolism. Normalization of the regional measures by whole brain metabolism (relative measures) showed that ethanol decreased relative metabolic activity in occipital cortex (-4.9 +/- 4.1%, p < or = 0.006), whereas it increased relative metabolic act in left temporal cortex (+3.5 +/- 2.9%, p < or = 0.006) and left basal ganglia (+9 +/- 6.3%, p < or = 0.0009). SPM analyses revealed the same pattern of responses as the relative measures, showing decreases in occipital cortex and increases in left temporal cortex. Comparison of the relative measures and the SPM analyses obtained with lorazepam data revealed a similar pattern of effects, with relative decreases in occipital cortex (-7.8 +/- 4.8%) and relative increases in left temporal cortex (+3.8 +/- 5.7%). Lorazepam, but not ethanol, also decreased thalamic metabolism (-11.2 +/- 7.2%). CONCLUSIONS: These results support similar though not identical mechanisms for the effects of alcohol and benzodiazepines on brain glucose metabolism. The fact that lorazepam, but not alcohol, reduced thalamic metabolism, an effect associated with sleepiness, could explain the higher sedative effects of lorazepam than of alcohol.

Adult↗

PubMed2000

PET studies of the effects of aerobic exercise on human striatal dopamine release.

UNLABELLED: In vivo microdialysis studies have shown that exercise increases the concentration of dopamine (DA) in the striatum of the rat brain. It has also been shown that PET with [11C]raclopride can be used to assess changes in brain DA induced by drugs and by performance tasks such as playing a video game. The purpose of this study was to evaluate the effects of exercise (treadmill running) on striatal DA release in the human brain. METHODS: Twelve healthy volunteers (5 women, 7 men; mean age, 32 +/- 5 y; age range, 25-40 y) with a history of regular exercise received 2 PET scans with [11C]raclopride on 2 separate days, 1 at baseline and 1 at 5-10 min after running on a treadmill for 30 min. The speed and inclination of the treadmill were increased gradually to reach a maximal speed of 9.7 km/h (6 mph) and a maximal inclination of 10degrees. Data were acquired on a Siemens HR+ scanner in 3-dimensional mode for 60 min. Heart rates and electrocardiograms were monitored. DA D2 receptor availability was measured using the ratio of the distribution volume in the putamen to that in the cerebellum, which is a function of the number of available binding sites/dissociation constant. RESULTS: The subjects ran at an average speed of 8.7 +/- 0.5 km/h (5.4 +/- 0.3 mph) and at an inclination of 3.3degrees +/- 2degrees. The maximum effort of running was maintained for 10-15 min. The heart rates of the subjects were increased by 143% +/- 47%. DA D2 receptor availability in the putamen after treadmill running (4.22 +/- 0.34) was no different from that of baseline (4.17 +/- 0.29; P < 0.6). CONCLUSION: No significant changes in synaptic DA concentration were detected, although the subjects exercised vigorously for 30 min.

Adult↗

PubMed1999

Mucosal modulation of agonist-induced myosin phosphorylation and contraction in airway smooth muscle.

We investigated the mechanism of mucosal modulation of airway smooth muscle contraction by measuring concentration- and length dependencies of carbachol-induced active stress and myosin phosphorylation in mucosa-intact and mucosa-free bovine tracheal smooth muscle. The concentration dependencies of carbachol-induced active stress in mucosa-intact and mucosa-free smooth muscles were significantly different in maximum but not in half-maximal concentration (EC50). Similar mucosa-dependent difference in maximum was also observed in the concentration dependence of carbachol-induced myosin phosphorylation. As a result, the myosin phosphorylation-active stress relations in mucosa-intact and mucosa-free smooth muscles were not significantly different. Length dependence of carbachol-induced active stress was significant in mucosa-intact smooth muscle, and accompanied by significant length dependence of myosin phosphorylation. These results suggest that the primary effect of mucosal modulation is inhibition of myosin light chain phosphorylation without uncoupling of active stress from myosin phosphorylation in airway smooth muscle.

Animals↗

PubMed1999

Regional brain metabolic activation during craving elicited by recall of previous drug experiences.

Cocaine cues elicit craving and physiological responses. The cerebral circuits involved in these are poorly understood. The purpose of this study was to assess the relation between regional brain activation and cocaine cue elicited responses. Thirteen right-handed cocaine abusers were scanned with positron emission tomography (PET) and [F-18] fluorodeoxyglucose (FDG) twice; during an interactive interview about neutral themes and during an interactive interview about cocaine themes designed to elicit cocaine craving. In parallel the behavioral (rated from 0: felt nothing to 10: felt extreme) and cardiovascular responses were recorded. During the cocaine theme interview subjects reported higher self reports for cocaine craving (+2.5+/-3.3, p < or = 0.02) and had higher heart rates (+4.7+/-7.2%, p < or = 0.001), systolic (+4+/-4%, p < or = 0.0001), and diastolic blood pressures (+2.6+/-3.8%, p < or = 0.003) than during the neutral interview. Absolute and relative metabolic values in the orbitofrontal (+16.4+/-17.1%, p < or = 0.005; +11.3+/-14.3%, p < or = 0.008) and left insular cortex (+21.6+/-19.6%, p < or = 0.002; +16.7+/-19.7%, p < or = 0.01) and relative values in cerebellum (+17.9+/-14.8%, p < or = 0.0008) were higher during the cocaine theme than during the neutral theme interview. Relative metabolic values in the right insular region (p < or = 0.0008) were significantly correlated with self reports of cocaine craving. Activation of the temporal insula, a brain region involved with autonomic control, and of the orbitofrontal cortex, a brain region involved with expectancy and reinforcing salience of stimuli, during the cocaine theme support their involvement with craving in cocaine addicted subjects.

Adult↗

PubMed1999

Measuring reproducibility of regional brain metabolic responses to lorazepam using statistical parametric maps.

UNLABELLED: Statistical parametric mapping (SPM) is a method for localizing differences in brain activation patterns without the need for anatomic predefined constraints. The purpose of this study was to assess the reproducibility of the patterns of activation obtained with SPM for baseline measures and for metabolic changes in response to lorazepam on a test-retest design. The results were compared with those we previously published using region-of-interest (ROI) methods. METHODS: Sixteen healthy right-handed men were scanned twice with PET and [18F]fluorodeoxyglucose (FDG): before placebo and before lorazepam (30 microg/kg). The same double FDG procedure was repeated 6-8 wk later to assess test-retest reproducibility. Image datasets were analyzed by using SPM95 software. Difference images between baseline and lorazepam were compared for the first and second evaluations, both for relative decreases as well as increases in metabolism. Significance level was systematically varied to P < 0.001, P < 0.01 and P < 0.05. RESULTS: There were no differences in the baseline SPM maps obtained for the first and second evaluations. SPM showed similar, although not identical, differences in response to lorazepam between the two evaluations. Both evaluations showed significant decreases in occipital cortex (9.7% and 10%) and significant relative increases in left temporal pole (6.8% and 10.4%). However, the second evaluation showed a decrease in the left frontal cortex (areas 6 and 8), which was not present in the first evaluation. The results were very similar to those we had obtained with ROI methods, except for the activation in the left temporal pole, which we had not observed with ROI analyses. CONCLUSION: Although the overall pattern of lorazepam-induced activation depicted by SPM was reproducible in pattern and magnitude, there were some differences that included a left frontal area of deactivation during the second but not the first evaluation. Results with SPM are similar to those with the ROI method, and, because it systematically analyses the whole brain, SPM can uncover patterns not seen with the ROI method.

Adult↗

PubMed1999

Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate.

UNLABELLED: The measure of changes in synaptic dopamine (DA) concentration in response to the psychostimulant drug methylphenidate (MP) has been used as an indicator of responsiveness of the DA system. The purpose of this study was to assess the reproducibility of these measures. METHODS: Seven healthy subjects were scanned with PET and [11C]raclopride twice in the same day: 7 min after placebo or methylphenidate (0.5 mg/kg) administration. In parallel we also measured the physiologic and behavioral responses to placebo and to methylphenidate. The same procedures were repeated 1-2 wk later to assess test-retest reproducibility. RESULTS: Measures of plasma to brain transfer constant (K1), striatal distribution volume (DVstr) and DA D2 receptor availability (Bmax/Kd), for the placebo condition were similar for the first (E1) and second (E2) evaluations (Bmax/Kd, E1: 2.77+/-0.44; E2: 2.97+/-0.44). MP administration did not change K1, but it significantly decreased DVstr (E1: -25.9%+/-8.7%, P < or = 0.0002; E2: -20.7%+/-11.7%, P < or = 0.007) and Bmax/Kd (E1: -18.4%+/-8.7%, P < or = 0.002; E2: -13.4%+/-9.2%, P < or = 0.008), and the magnitude of these changes, though lower for E2, did not differ significantly. MP increased pulse rate (E1: +64%+/-43%, P < or = 0.002; E2: +69%+/-33%, P < or = 0.001), systolic pressure (E1: +37%+/-19%, P < or = 0.0006; E2: +29%+/-15%, P < or = 0.0009), self reports for drug effects (0: nothing to 10: extreme) of "rush" (E1: +8+/-3, P < or = 0.0004; E2: +6+/-4, P < or = 0.01) and "high" (E1: +8+/-3, P < or = 0.0001, E2: +8+/-3, P < or = 0.0003), anxiety (E1: +5+/-4, P < or = 0.02; E2: +4+/-4, P = 0.1) and restlessness (E1: +4+/-4, P < or = 0.04; E2: +4+/-5, P = 0.1). The magnitude of the cardiovascular and behavioral effects did not differ between E1 and E2. CONCLUSION: MP-induced changes in striatal DV and in Bmax/Kd, as well as the behavioral and cardiovascular effects, were reproducible with repeated administration.

Adult↗

PubMed1998

Brewer's yeast and Saccharomyces boulardii both attenuate Clostridium difficile-induced colonic secretion in the rat.

Saccharomyces boulardii (Sb), a nonpathogenic yeast, has been used to prevent recurrences of Clostridium difficile (C.diff) -associated diarrhea. A single report suggested that treatment with Saccharomyces cerevisiae (Sc), commonly called brewer's yeast (BY), facilitates treatment of persistent C.diff infection. We conducted this experiment to determine whether C.diff toxin A-induced colonic secretion in the rat is blunted by pretreatment with either Sb or BY. We employed closed cecal pouches in two groups of five adult male Sprague-Dawley rats fed with standard chow for five days prior to the experiment, another group whose water was supplemented with 20 x 10(9) colony-forming units (CFU) of Sb per day for five days, and another group whose water was supplemented with 20 x 10(9) CFU of Sc per day for five days. Cecal pouches were infused for 3 hr with one of the following: (1) normal saline alone for a control group, or (2) normal saline plus 5 microg of C.diff toxin A (for the other control group and for the two experimental groups). Water movement was measured by a nonabsorbable marker technique. Sodium movement and permeability to mannitol were also measured. Prior to the infusion, cecal contents were quantitatively cultured. In the three animals whose ceca were colonized with less than 10(6) CFU of either yeast per gram wet cecal content, toxin A-induced secretion could not be attenuated. In contrast, animals whose ceca were colonized with more than 10(6) CFU of either yeast per gram of wet cecal content showed significantly less secretion after toxin A application than those which were not fed yeast. S. cerevisiae reduced secretion by half (N = 5, P = 0.039 for water, 0.044 for sodium) and Sb by 75% (N = 4, P = 0.015 for water, 0.034 for sodium). Toxin-induced increases in permeability to [3H]mannitol from systemic circulation to cecum could not be blunted by either yeast. We conclude that rat ceca can be colonized by either organism and that both organisms reduce C.diff toxin A-mediated secretion. We speculate that both organisms might have benefit in human C.diff-associated enterocolitis. Further studies of their mechanisms of action as well as clinical trials for the prevention and treatment of human C.diff infections should be pursued.

Animals↗

PubMed1998

Imaging the brain marijuana receptor: development of a radioligand that binds to cannabinoid CB1 receptors in vivo.

The major active ingredient of marijuana, (-)-delta9-tetrahydrocannabinol, exerts its psychoactive effects via binding to cannabinoid CB1 receptors, which are widely distributed in the brain. Radionuclide imaging of CB1 receptors in living human subjects would help explore the presently unknown physiological roles of this receptor system, as well as the neurochemical consequences of marijuana dependence. Currently available cannabinoid receptor radioligands are exceedingly lipophilic and unsuitable for in vivo use. We report the development of a novel radioligand, [123I]AM281[N-(morpholin-4-yl)-5-(4-[123I]iodophenyl)-1-(2,4 -dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], that is structurally related to the CB1-selective antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-me thyl-1H-pyrazole-3-carboxamide]. Baboon single photon emission computed tomography studies, mouse brain dissection studies, and ex vivo autoradiography in rat brain demonstrated rapid passage of [123I]AM281 into the brain after intravenous injection, appropriate regional brain specificity of binding, and reduction of binding after treatment with SR141716A. AM281 has an affinity in the low nanomolar range for cerebellar binding sites labeled with [3H]SR141716A in vitro, and binding of [123I]AM281 is inhibited by several structurally distinct cannabinoid receptor ligands. We conclude that [123I]AM281 has appropriate properties for in vivo studies of cannabinoid CB1 receptors and is suitable for imaging these receptors in the living human brain.

Animals↗

PubMed1998

Regional cerebral metabolism in female alcoholics of moderate severity does not differ from that of controls.

It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [18F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism.

Adult↗

PubMed1996

Acute phase proteins in male Chinese schizophrenic patients in Singapore.

Changes in the concentration of some serum acute phase proteins (alpha 1-antitrypsin, alpha 2-macroglobulin, complement C3, haptoglobin, ceruloplasmin, transferrin, albumin and hemopexin), thyroxine-binding globulin, retinol-binding globulin, plasminogen and Gc-globulin are reported in two separate series of Chinese, male schizophrenic patients and healthy controls. In the first series, 41 healthy blood donors and 98 schizophrenic patients in different stages of the disease were investigated. The second series consists of a random sample of 50 acutely ill schizophrenic patients and a second group of healthy subjects. The concentrations of these serum proteins were measured by rocket immunoelectrophoresis in agarose gel. Increased levels of serum alpha 1-antitrypsin, alpha 2-macroglobulin, haptoglobin, ceruloplasmin, and thyroxine-binding globulin were observed in both series of patients when compared to their respective controls. Albumin, transferrin and retinol-binding protein levels were reduced in patients in both series. Hemopexin levels were increased only in the acutely ill patients while complement C3 was decreased in the chronically ill patients. No changes were observed in the Gc-globulin levels of all groups of patients. With the exception of complement C3, the changes observed in the levels of these serum proteins were appropriate for that of an acute phase response.

Acute Disease↗

PubMed1996

Quantitative 123I IMP and 99mTc HMPAO imaging in the dog following cocaine administration.

SPECT and associated imaging procedures were used in beagle dogs to (1) evaluate the uptake, distribution, and clearance properties of i.v.-injected 123I IMP (IMP) and 99mTc HMPAO (HMPAO) in the brain, lungs, liver, and kidneys; (2) quantify the acute effects (after 15 sec) of very low doses (0.5 or 1.0 mg/kg) cocaine on the kinetics and localization properties of IMP and HMPAO; and (3) evaluate comparative imaging properties of IMP and HMPAO for measuring regional cerebral blood flow (rCBF). Regional and global uptake and localization of IMP or HMPAO were evaluated in control studies using dynamic planar (0-30 min) and SPECT imaging (at 35 min). The regional distribution properties of IMP and HMPAO in the brain were estimated from regions of interest (ROIs) drawn around anatomic structures on MR slices and manually registered with corresponding SPECT slices. Cocaine significantly reduced the 30-min IMP uptake in the brain and lungs by approximately 15%, but only slightly changed HMPAO uptake in the brain and other organs. In the control studies, the respective uptakes of IMP in the brain and lungs were 9 and 39% greater (p < 0.01) than those of HMPAO. In control SPECT studies, the highest uptake of IMP was observed in the thalamus and progressively less activity was observed in the parietal lobe, frontal lobe, cerebellum, occipital lobe, and entire brain; activity in the olfactory bulb was lower than in all other regions. Cocaine reduced IMP uptake in the cerebellum (p < 0.01), occipital lobe (p < 0.01), and entire brain (p < 0.05). IMP uptake (cpm/pixel-mCi) in the different brain regions was 1.3 to 2.1 times greater than that of HMPAO (p < 0.001). HMPAO uptake was more homogeneous throughout the gray matter of the brain; no significant uptake differences were observed among flagged regions. Results indicate that single, acute doses of cocaine, 0.5 and 1.0 mg/kg, significantly altered the uptake and localization properties of IMP in the dog's brain, lungs, liver, and kidneys. Variations in regional uptake of IMP in the parietal, frontal, and occipital lobes, cerebellum, and thalamus were greater than with HMPAO.

Amphetamines↗