Biomedical subjects

G J Wang

Publications and source records attributed to G J Wang.

At least 19 recordsLinked to original sources

PubMed2006

Poverty and the economic effects of TB in rural China.

OBJECTIVE: To investigate the economic effects of illness on individual tuberculosis (TB) cases in rural China and to use a case-control study to show a strong TB-poverty link. SETTING: In 2002-2004 we studied 160 new smear-positive pulmonary tuberculosis (PTB) cases and 320 age- and sex-matched controls living in neighbouring houses in four rural counties of Henan Province. DESIGN: Cases and controls were interviewed 1-3 months after patients were diagnosed. We used matched multivariate logistic regression to compare cases with controls for poverty status using household income, household assets and relative wealth within the village. We conducted follow-up interviews of patients 10-12 months later to assess economic effects by collecting data on treatment costs, income losses, coping strategies and treatment completion. RESULTS: Poverty is strongly associated with TB incidence even after controlling for smoking and other risk factors. Excluding income losses, direct out-of-pocket treatment costs (medical and non-medical) accounted for 55.5% of average annual household income, and most TB cases fell into heavy debt. The DOTS cure rate was 91%. When DOTS was incomplete or not done, mortality was high. CONCLUSIONS: Poverty is both a cause and a devastating outcome of TB. Ongoing poverty reduction schemes in China must also include reducing TB.

Adult↗

PubMed2003

Hemocompatibility of titanium oxide films.

Hemocompatibility is a key property of biomaterials that come in contact with blood. Surface modification has shown great potential for improving the hemocompatibility of biomedical materials and devices. In this paper, we describe our work of improving hemocompatibility with Ti-O thin films prepared by plasma immersion ion implantation and deposition and by sputtering. The structure and surface chemical and physical properties of the films were characterized by X-ray diffraction, Auger electron spectroscopy, atomic force microscopy (AFM), contact angle measurement, and Hall effect measurement. The behavior of fibrinogen adsorption was investigated by 125I radioactive isotope labeling and AFM. Systematic evaluation of hemocompatibility, including in vitro clotting time, thrombin time, prethrombin time, platelet adhesion, and in vivo implantation into dog's ventral aorta or right auricle from 17 to 90 days, proved that Ti-O films have excellent hemocompatibility. It is suggested that the significantly lower interface tension between Ti-O films and blood and plasma proteins and the semiconducting nature of Ti-O films give them their improved hemocompatibility.

Adsorption↗

PubMed2002

Mild hypothermia reduces ICAM-1 expression, neutrophil infiltration and microglia/monocyte accumulation following experimental stroke.

Mild hypothermia is an established neuroprotectant against cerebral ischemic injury. Studies have shown that inflammation potentiates cerebral ischemic injury, particularly in the setting of reperfusion. To further elucidate the mechanism by which mild hypothermia attenuates the inflammatory response, we assessed endothelial intercellular adhesion molecule-1 (ICAM-1) expression, neutrophil and monocyte infiltration, and microglial activation following 2 h of transient focal cerebral ischemia under normothermic and mildly hypothermic conditions. Ischemia was induced using the intraluminal suture method in Sprague-Dawley rats. Immunohistochemistry was used to detect endothelial ICAM-1, infiltrating neutrophils and monocytes, and microglia at 1, 3, and 7 days post-ischemia. Immunopositive cell and vessel densities were measured in the peri-infarct region. Mild hypothermia was associated with decreased neutrophils at 1 and 3 days post-ischemia, decreased ICAM-1-positive vessels at 1, 3, and 7 days, and decreased monocytes/activated microglia at 3 and 7 days, but not at 1 day. These data demonstrate that mild hypothermia significantly reduces endothelial adhesion molecule expression, acute (neutrophil) and subacute (monocyte) leukocyte infiltration, and microglial activation up to 7 days following insult in a rodent model of transient focal cerebral ischemia.

Animals↗

PubMed2002

Rapid effect of progesterone on the contraction of rat aorta in-vitro.

Progesterone induced rapid relaxation of KCl-induced contraction of rat aortic rings. The relaxant effect of progesterone on aortic rings was concentration-dependent (over the range of 10(-10) to 10(-5) M) and partially dependent on the endothelium. Application of a nitric oxide (NO) synthase antagonist N(G)-monomethyl-L-arginine (L-NMMA, 10(-5) M) after progesterone treatment partially inhibited the relaxant effects of progesterone. This suggested that part of the effect was through the production of nitric oxide. Washing out the steroid hormone in the bath solutions could quickly reverse the inhibitory effects of progesterone on phasic tension generation in aortic rings. Five minutes after washout, the tension generation in aortic rings was completely restored. Cultured endothelial cells from rat aorta increased release of NO into culture media in response to a 60-min exposure to progesterone. Aldosterone and dexamethasone were also tested, and failed to relax KCl-induced contraction of aortic rings. These data suggest that the vascular effects of progesterone are not mediated by a genomic action of this steroid, and that the vascular effects are mediated partially through endothelial NO production.

Aldosterone↗

PubMed2001

Loss of dopamine transporters in methamphetamine abusers recovers with protracted abstinence.

Methamphetamine is a popular drug of abuse that is neurotoxic to dopamine (DA) terminals when administered to laboratory animals. Studies in methamphetamine abusers have also documented significant loss of DA transporters (used as markers of the DA terminal) that are associated with slower motor function and decreased memory. The extent to which the loss of DA transporters predisposes methamphetamine abusers to neurodegenerative disorders such as Parkinsonism is unclear and may depend in part on the degree of recovery. Here we assessed the effects of protracted abstinence on the loss of DA transporters in striatum, in methamphetamine abusers using positron emission tomography and [(11)C]d-threo-methylphenidate (DA transporter radioligand). Brain DA transporters in five methamphetamine abusers evaluated during short abstinence (<6 months) and then retested during protracted abstinence (12-17 months) showed significant increases with protracted abstinence (caudate, +19%; putamen, +16%). Although performance in some of the tests for which we observed an association with DA transporters showed some improvement, this effect was not significant. The DA transporter increases with abstinence could indicate that methamphetamine-induced DA transporter loss reflects temporary adaptive changes (i.e., downregulation), that the loss reflects DA terminal damage but that terminals can recover, or that remaining viable terminals increase synaptic arborization. Because neuropsychological tests did not improve to the same extent, this suggests that the increase of the DA transporters was not sufficient for complete function recovery. These findings have treatment implications because they suggest that protracted abstinence may reverse some of methamphetamine-induced alterations in brain DA terminals.

Adult↗

PubMed2001

Comparison of lumbar spine fusion using mixed and cloned marrow cells.

STUDY DESIGN: Prospective study on lumbar spine fusion using cloned and mixed marrow cells. OBJECTIVE: To analyze the effectiveness of cloned osteoprogenitor cells in spine fusion and their differentiation in vivo using a traceable gene. SUMMARY OF BACKGROUND DATA: Although autografts are currently the standard for stable spine fusion, supply is limited. Alternative graft materials need to be developed and evaluated. METHODS: An osteoprogenitor cell, D1-BAG, cloned from mouse bone marrow and transduced with LacZ and neomycin resistance genes, and mixed marrow stromal cells from marrow blowouts were used in athymic rats to establish posterior spinal fusion; 2 x 10(6) cells in 100 microL Matrigel were implanted into the lumbar fusion bed in 36 animals, whereas Matrigel without cells was used in 16 animals as control. Rats were killed at 2, 3, 6, and 9 weeks, and the spines were evaluated by manual palpation, radiographs, and histology. RESULTS: Two weeks after surgery radiopaque tissue was seen at transplantation sites with D1-BAG cells but not at sites with mixed marrow stromal cells. Successful spine fusion at 6 and 9 weeks was observed in 8 of 8 (100%) animals receiving DI-BAG cells, 4 of 8 (50%) in mixed marrow stromal cells, and 0 of 8 (0%) in control animals. CONCLUSIONS: Compared with mixed marrow stromal cells, cloned osteoprogenitor cells can produce a larger amount of mature osseous tissue at an earlier time point during spine fusion.

Animals↗

PubMed2001

Addiction changes orbitofrontal gyrus function: involvement in response inhibition.

We used the Stroop task as a measure of the ability to inhibit a prepotent response tendency and examined its association with relative glucose metabolism in selected prefrontal brain regions in cocaine addicts, alcoholics, and controls (17 per group). Results revealed that for the substance abusers, higher orbitofrontal gyrus (OFG) activation was associated with lower conflict (higher score; r = 0.32, p < 0.05). For the controls, higher OFG activation was associated with higher conflict (lower score; r = -0.42, p < 0.05). Thus, at baseline, increased relative activation of the OFG is associated with worse performance in controls and better performance in substance abusers on the Stroop task, suggesting reversal of the role of the OFG as a function of addiction.

Adult↗

PubMed2001

Inhibitory effect of evodiamine on aldosterone release by Zona glomerulosa cells in male rats.

Evodiamine is a bioactive alkaloid extracted from a Chinese herb named Wu-Chu-Yu, which possesses thermoregulatory, analgesic, and cardiovascular effects. Some studies have demonstrated that evodiamine reduces blood pressure through acting on endothelium and smooth muscle cells to produce a vasodilatory effect, but whether it affects aldosterone secretion is unclear. The purpose of this study was to examine the effect of evodiamine on aldosterone release in adrenal zona glomerulosa (ZG) cells. ZG cells were isolated from the adrenal glands of adult male rats and incubated with angiotensin II (Ang II, 1x10(-7) M) and 3H-pregnenolone in the presence or absence of evodiamine (1x10(-6)-1x10(-3) M) at 37 degrees C for one hour. The concentration of aldosterone in the media was measured by a radioimmunoassay. The level of radioactivity incorporated into aldosterone and its precursors after incubation of ZG cells with 3H-pregnenolone was analyzed by thin-layer chromatography. The results demonstrated that evodiamine decreased the basal level of and Ang II-induced release level of aldosterone in rat ZG cells. Administration of evodiamine also decreased the level of radioactivity incorporated into 3H-corticosterone and 3H-aldosterone following incubation of ZG cells with 3H-pregnenolone. This suggest that evodiamine affects aldosterone release in rat adrenal glomerulosa cells by acting on Ang II-associated pathway and reducing the activity of 11 beta-hydroxylase (an enzyme which coverts deoxycorticosterone to corticosterone) during the steroidogenesis of aldosterone.

Aldosterone↗

PubMed2001

Evidence that L-deprenyl treatment for one week does not inhibit MAO A or the dopamine transporter in the human brain.

In this study, we investigated whether treatment with L-deprenyl, a selective monoamine oxidase B (MAO B) inhibitor, also inhibits MAO A or the dopamine transporter in the human brain. Six normal volunteers (age 46+/-6 yrs) had two PET sessions, one at baseline and one following L-deprenyl (10 mg/day) for 1 week. Each session included one scan with [11C]clorgyline (to assess MAO A) and one scan 2 hours later with [11C]cocaine (to assess dopamine transporter availability). A 3-compartment model was used to compare the plasma-to-brain transfer constant, K1 (a function of blood flow) and lambdak3 (a kinetic term proportional to brain MAO A) before and after treatment. Dopamine transporter availability was measured as the ratio of distribution volumes of the striatum to cerebellum (DVR) which is equal to Bmax/KD +1. L-Deprenyl treatment for 1 week did not affect either brain MAO A activity or dopamine transporter availability. There was a non-significant trend for an increase in K1 after L-deprenyl. These results confirm that L-deprenyl after one week of treatment at doses typically used clinically is selective for MAO B and that it does not produce a measurable affect on the dopamine transporter, suggesting that MAO A inhibition and dopamine transporter blockade do not contribute to its pharmacological effects.

Adult↗

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↗

PubMed2001

[(11)]Cocaine: PET studies of cocaine pharmacokinetics, dopamine transporter availability and dopamine transporter occupancy.

Cocaine was initially labeled with carbon-11 in order to track the distribution and pharmacokinetics of this powerful stimulant and drug of abuse in the human brain and body. It was soon discovered that [(11)C]cocaine was not only useful for measuring cocaine pharmacokinetics and its relationship to behavior but that it is also a sensitive radiotracer for dopamine transporter (DAT) availability. Measures of DAT availability were facilitated by the development of a graphical analysis method (Logan Plot) for reversible systems which streamlined kinetic analysis. This expanded the applications of [(11)C]cocaine to studies of DAT availability in the human brain and allowed the first comparative measures of the degree of DAT occupancy by cocaine and another stimulant drug methylphenidate. This article will summarize preclinical and clinical research with [(11)C]cocaine.

Brain↗

PubMed2001

Species differences in [11C]clorgyline binding in brain.

[11C]Clorgyline selectively binds to MAO A in the human brain. This contrasts with a recent report that [11C]clorgyline (in contrast to other labeled MAO A inhibitors) is not retained in the rhesus monkey brain [4]. To explore this difference, we compared [11C]clorgyline in the baboon brain before and after clorgyline pretreatment and we also synthesized deuterium substituted [11C]clorgyline (and its nor-precursor) for comparison. [11C]Clorgyline was not retained in the baboon brain nor was it influenced by clorgyline pretreatment or by deuterium substitution, contrasting to results in humans. This suggests a species difference in the susceptibility of MAO A to inhibition by clorgyline and represents an unusual example of where the behavior of a radiotracer in the baboon brain does not predict its behavior in the human brain.

Animals↗

PubMed2001

Non-MAO A binding of clorgyline in white matter in human brain.

Clorgyline is an irreversible inhibitor of monoamine oxidase (MAO A) which has been labeled with carbon-11 (C-11) and used to measure human brain MAO A with positron emission tomography (PET). In this study we compared [11C]clorgyline and deuterium-substituted [11C]clorgyline ([11C]clorgyline-D2) to better understand the molecular link between [11C]clorgyline binding and MAO A. In PET studies of five normal healthy volunteers scanned with [11C]clorgyline and [11C]clorgyline-D2 2 h apart, deuterium substitution generally produced the expected reductions in the brain uptake of [11C]clorgyline. However, the reduction was not uniform with the C-11 binding in white matter being significantly less sensitive to deuterium substitution than other brain regions. The percentages of the total binding attributable to MAO A is largest for the thalamus and smallest for the white matter and this is clearly seen in PET images with [11C]clorgyline-D2. Thus deuterium-substituted [11C]clorgyline selectively reduces the MAO A binding component of clorgyline in the human brain revealing non-MAO A binding which is most apparent in the white matter. The characterization of the non-MAO A binding component of this widely used MAO A inhibitor merits further investigation.

Adult↗

PubMed2001

Comparative strength of three methods of fixation of transverse acetabular fractures.

With the advent of percutaneously placed lag screws for fixation of acetabular fractures, this study evaluated the strength of lag screw fixation compared with traditional fixation techniques of transverse acetabular fractures. Ten formalin-treated human, cadaveric pelvic specimens with bilateral, transtectal transverse acetabular fractures were used for this study. The right acetabular fractures were fixed with a five-hole plate and four screws with the central hole spanning the posterior fracture site. The left acetabular fractures were fixed with two lag screws, one each in the anterior and posterior columns, or with a screw and wire construct stabilizing both columns. The specimens were loaded to implant failure. Stiffness, yield strength, maximum load at failure, and site of failure was recorded. The plate and screw construct showed significantly greater yield and maximum strength when compared with the two lag screws. The stiffness of the lag screw method was 39% higher than that of the plating method, but this result was not statistically significant. In addition, the plate and screw method provided significantly greater maximum strength than the screw and wire technique. The quadrilateral plate seemed to be the weakest area of fixation because 83% of the implant failures occurred in this region. In patients in whom the risks of formal open reduction and internal fixation of acetabular fractures outweigh the possible benefits, such as in patients with burns or degloved skin, the advent of computer-assisted and fluoroscopically guided percutaneous surgical techniques have been instrumental. This study showed there is greater strength of fixation with a plate and screw construct, possibly secondary to supplementary fixation distal to the quadrilateral plate. However, lag screw fixation provided relatively greater stiffness, which may account for its clinical success. Percutaneous lag screw fixation of appropriate transverse acetabular fractures is a viable option.

Acetabulum↗

PubMed2001

A strategy for removing the bias in the graphical analysis method.

The graphical analysis method, which transforms multiple time measurements of plasma and tissue uptake data into a linear plot, is a useful tool for rapidly obtaining information about the binding of radioligands used in PET studies. The strength of the method is that it does not require a particular model structure. However, a bias is introduced in the case of noisy data resulting in the underestimation of the distribution volume (DV), the slope obtained from the graphical method. To remove the bias, a modification of the method developed by Feng et al. (1993), the generalized linear least squares (GLLS) method, which provides unbiased estimates for compartment models was used. The one compartment GLLS method has a relatively simple form, which was used to estimate the DV directly and as a smoothing technique for more general classes of model structures. In the latter case, the GLLS method was applied to the data in two parts, that is, one set of parameters was determined for times 0 to T1 and a second set from T1 to the end time. The curve generated from these two sets of parameters then was used as input to the graphical method. This has been tested using simulations of data similar to that of the PET ligand [11C]-d-threo-methylphenidate (MP, DV = 35 mL/mL) and 11C raclopride (RAC, DV = 1.92 mL/mL) and compared with two examples from image data with the same tracers. The noise model was based on counting statistics through the half-life of the isotope and the scanning time. Five hundred data sets at each noise level were analyzed. Results (DV) for the graphical analysis (DV(G)), the nonlinear least squares (NLS) method (DV(NLS)), the one-tissue compartment GLLS method (DV(F)), and the two part GLLS followed by graphical analysis (DV(FG)) were compared. DV(FG) was found to increase somewhat with increasing noise and in some data sets at high noise levels no estimate could be obtained. However, at intermediate levels it provided a good estimation of the true DV. This method was extended to use a reference tissue in place of the input function to generate the distribution volume ratio (DVR) to the reference region. A linearized form of the simplified reference tissue method of Lammertsma and Hume (1996) was used. The DVR generated directly from the model (DVR(FL)) was compared with DVR(FG) (determined from a "smoothed" uptake curve as for DV(FG)) using the graphical method.

Artifacts↗

PubMed2001

Low level of brain dopamine D2 receptors in methamphetamine abusers: association with metabolism in the orbitofrontal cortex.

OBJECTIVE: The role of dopamine in the addictive process (loss of control and compulsive drug intake) is poorly understood. A consistent finding in drug-addicted subjects is a lower level of dopamine D2 receptors. In cocaine abusers, low levels of D2 receptors are associated with a lower level of metabolism in the orbitofrontal cortex. Because the orbitofrontal cortex is associated with compulsive behaviors, its disruption may contribute to compulsive drug intake in addicted subjects. This study explored whether a similar association occurs in methamphetamine abusers. METHOD: Fifteen methamphetamine abusers and 20 non-drug-abusing comparison subjects were studied with positron emission tomography (PET) and [11C]raclopride to assess the availability of dopamine D2 receptors and with [18F]fluorodeoxyglucose to assess regional brain glucose metabolism, a marker of brain function. RESULTS: Methamphetamine abusers had a significantly lower level of D2 receptor availability than comparison subjects (a difference of 16% in the caudate and 10% in the putamen). D2 receptor availability was associated with metabolic rate in the orbitofrontal cortex in abusers and in comparison subjects. CONCLUSIONS: Lower levels of dopamine D2 receptor availability have been previously reported in cocaine abusers, alcoholics, and heroine abusers. This study extends this finding to methamphetamine abusers. The association between level of dopamine D2 receptors and metabolism in the orbitofrontal cortex in methamphetamine abusers, which replicates previous findings in cocaine abusers, suggests that D2 receptor-mediated dysregulation of the orbitofrontal cortex could underlie a common mechanism for loss of control and compulsive drug intake in drug-addicted subjects.

Adult↗

PubMed2001

Association of dopamine transporter reduction with psychomotor impairment in methamphetamine abusers.

OBJECTIVE: Methamphetamine is a popular and highly addictive drug of abuse that has raised concerns because it has been shown in laboratory animals to be neurotoxic to dopamine terminals. The authors evaluated if similar changes occur in humans and assessed if they were functionally significant. METHOD: Positron emission tomography scans following administration of [(11)C]d-threo-methylphenidate (a dopamine transporter ligand) measured dopamine transporter levels (a marker of dopamine cell terminals) in the brains of 15 detoxified methamphetamine abusers and 18 comparison subjects. Neuropsychological tests were also performed to assess motor and cognitive function. RESULTS: Methamphetamine abusers showed significant dopamine transporter reduction in the striatum (mean differences of 27.8% in the caudate and 21.1% in the putamen) relative to the comparison subjects; this reduction was evident even in abusers who had been detoxified for at least 11 months. Dopamine transporter reduction was associated with motor slowing and memory impairment. CONCLUSIONS: These results provide evidence that methamphetamine at dose levels taken by human abusers of the drug leads to dopamine transporter reduction that is associated with motor and cognitive impairment. These results emphasize the urgency of alerting clinicians and the public of the long-term changes that methamphetamine can induce in the human brain.

Adult↗

PubMed2001

Higher cortical and lower subcortical metabolism in detoxified methamphetamine abusers.

OBJECTIVE: Methamphetamine has raised concerns because it may be neurotoxic to the human brain. Although prior work has focused primarily on the effects of methamphetamine on dopamine cells, there is evidence that other neuronal types are affected. The authors measured regional brain glucose metabolism, which serves as a marker of brain function, to assess if there is evidence of functional changes in methamphetamine abusers in regions other than those innervated by dopamine cells. METHOD: Fifteen detoxified methamphetamine abusers and 21 comparison subjects underwent positron emission tomography following administration of [(18)F]fluorodeoxyglucose. RESULTS: Whole brain metabolism in the methamphetamine abusers was 14% higher than that of comparison subjects; the differences were most accentuated in the parietal cortex (20%). After normalization for whole brain metabolism, methamphetamine abusers exhibited significantly lower metabolism in the thalamus (17% difference) and striatum (where the differences were larger for the caudate [12%] than for the putamen [6%]). Statistical parametric mapping analyses corroborated these findings, revealing higher metabolism in the parietal cortex and lower metabolism in the thalamus and striatum of methamphetamine abusers. CONCLUSIONS: The fact that the parietal cortex is a region devoid of any significant dopaminergic innervation suggests that the higher metabolism seen in this region in the methamphetamine abusers is the result of methamphetamine effects in circuits other than those modulated by dopamine. In addition, the lower metabolism in the striatum and thalamus (major outputs of dopamine signals into the cortex) is likely to reflect the functional consequence of methamphetamine in dopaminergic circuits. These results provide evidence that, in humans, methamphetamine abuse results in changes in function of dopamine- and nondopamine-innervated brain regions.

Adult↗