Xuyi Wang

Frontal white matter abnormalities following chronic ketamine use: a diffusion tensor imaging study

Ketamine abuse has been shown to have a deleterious impact on brain function. However, the precise mechanisms of ketamine dependence-induced pathological change remain poorly understood. Although there is evidence for white matter changes in drug abuse, the presence of white matter abnormalities in chronic ketamine users has not been studied. White matter volumes were measured using in vivo diffusion tensor magnetic resonance imaging data in 41 ketamine-dependent subjects and 44 drug-free healthy volunteers. White matter changes associated with chronic ketamine use were found in bilateral frontal and left temporoparietal cortices. There was also evidence that frontal white matter fractional anisotropy correlated with the severity of drug use (as measured by estimated total ketamine consumption). We provide direct evidence for dose-dependent abnormalities of white matter in bilateral frontal and left temporoparietal regions following chronic ketamine use. The findings suggest a microstructural basis for the changes in cognition and experience observed with prolonged ketamine use. Moreover, the similarities of these changes to those observed in chronic schizophrenia have implications for the glutamate model of this illness.

Reduced Dorsal Prefrontal Gray Matter After Chronic Ketamine Use

BACKGROUND Use of ketamine as a recreational drug is spreading rapidly among young people all over the world. Epidemiological studies have linked chronic ketamine use with a number of problems, including cognitive impairments, bladder dysfunction, and ketamine-related death. However, little is known about the long-term effects of ketamine use on brain structure and function. METHODS We used voxel based morphometry in conjunction with statistical parametric mapping on the structural magnetic resonance images of ketamine-dependent (n = 41) and drug-naive control individuals (n = 44) to assess differences in gray matter volume between the two groups. RESULTS We observed significant decreases in gray matter volume in bilateral frontal cortex (left superior frontal gyrus and right middle frontal gyrus) of ketamine users in comparison with control subjects (p < .05 corrected for multiple comparisons at cluster-level). Duration of ketamine use was negatively correlated with gray matter volume in bilateral frontal cortex, whereas the estimated total lifetime ketamine consumption was negatively correlated with gray matter volume in left superior frontal gyrus. CONCLUSIONS We have demonstrated a reduction in frontal gray matter volume in patients after chronic ketamine use. The link between frontal gray matter attenuation and the duration of ketamine use and cumulative doses of ketamine perhaps suggests a dose-dependent effect of long-term use of the drug. Our results have important connotations for the clinical picture that is likely to emerge with the growing recreational use of ketamine and is also relevant to the status of the drug as a model for schizophrenia.

Alcohol and alcohol-related harm in China: policy changes needed

In China, alcohol consumption is increasing faster than anywhere else in the world. A steady increase in alcohol production has also been observed in the country, together with a rise in alcohol-related harm. Despite these trends, Chinas policies on the sale and consumption of alcoholic beverages are weak compared with those of other countries in Asia. Weakest of all are its policies on taxation, drink driving laws, alcohol sale to minors and marketing licenses. The authors of this descriptive paper draw attention to the urgent need for public health professionals and government officials in China to prioritize population surveillance, research and interventions designed to reduce alcohol use disorders. They describe Chinas current alcohol policies and recent trends in alcohol-related harm and highlight the need for health officials to conduct a thorough policy review from a public health perspective, using as a model the World Health Organizations global strategy to reduce the harmful use of alcohol.

Nutrient delivery from the Mississippi River to the Gulf of Mexico and effects of cropland conservation

Excessive nutrients transported from the Mississippi River Basin (MRB) have created a hypoxic zone within the Gulf of Mexico, with numerous negative ecological effects. Furthermore, federal expenditures on agricultural conservation practices have received intense scrutiny in recent years. Partly driven by these factors, the USDA Conservation Effects Assessment Project (CEAP) recently completed a comprehensive evaluation of nutrient sources and delivery to the Gulf. The modeling framework used in the CEAP Cropland National Assessment, or Cropland CEAP, consists of the Agricultural Policy/Environmental eXtender (APEX) and Soil and Water Assessment Tool (SWAT) models. This CEAP modeling framework was successfully calibrated for flow, sediment, and nutrients at 38 sites and validated at an additional 17. Simulation results indicated that cultivated cropland was the dominant source of nitrogen (N) and phosphorus (P) to both local waters and the Gulf, but this was not true for each water resource region within the MRB. In addition, the results showed that point sources remain significant contributors of P loads, especially in the Tennessee and Arkansas/Red River basins where point source P loads exceeded those from cultivated cropland. Similarly, urban nonpoint sources were significant nutrient sources. The Upper Mississippi, Lower Mississippi, and Ohio basins contributed the largest amounts of nutrients delivered to the Gulf. The high delivery areas near the Mississippi River main stem, from which 87% of N and 90% of P was predicted to reach the Gulf, also coincided with elevated nutrient yields to local waters. Conservation practices established on agricultural lands within the MRB were predicted to have reduced nutrient loads to the Gulf by 20% as compared with a no conservation condition. The results indicate the importance of targeted implementation of conservation practices and consideration of local water and/or Gulf impacts depending on program goal(s). The present application illustrates the value of the Cropland CEAP modeling framework as a useful, science-based tool to evaluate pollutant sources and delivery and effects of agricultural conservation practices.

Changes in brain gray matter in abstinent heroin addicts

BACKGROUND Previous neuroimaging studies have documented changes in the brain of heroin addicts. However, few researches have detailed whether such changes can be amended after short-term abstinence. METHODS We used magnetic resonance imaging (MRI) to investigate gray matter volume in 20 heroin-dependent patients at 3 days and at 1 month after heroin abstinence; 20 normal subjects were also included as controls. RESULTS Decreased gray matter density in frontal cortex, cingulate and the occipital regions were found in heroin users after three days of abstinence. In contrast, after 1-month abstinence, no significant difference was found in superior frontal gyrus between heroin addicts and controls, but changes in other brain regions, including right middle frontal gyrus, left cingulate gyrus and left inferior occipital gyrus, still remained. CONCLUSION Our findings illustrate that abnormal gray matter in some brain regions of heroin addicts can return to normal after one-month abstinence.

Bilateral Fronto-Parietal Integrity in Young Chronic Cigarette Smokers: A Diffusion Tensor Imaging Study

Background Cigarette smoking continues to be the leading cause of preventable morbidity and mortality in China and other countries. Previous studies have demonstrated gray matter loss in chronic smokers. However, only a few studies assessed the changes of white matter integrity in this group. Based on those previous reports of alterations in white matter integrity in smokers, the aim of this study was to examine the alteration of white matter integrity in a large, well-matched sample of chronic smokers and non-smokers. Methodology/Principal Findings Using in vivo diffusion tensor imaging (DTI) to measure the differences of whole-brain white matter integrity between 44 chronic smoking subjects (mean age, 28.0±5.6 years) and 44 healthy age- and sex-matched comparison non-smoking volunteers (mean age, 26.3±5.8 years). DTI was performed on a 3-Tesla Siemens scanner (Allegra; Siemens Medical System). The data revealed that smokers had higher fractional anisotropy (FA) than healthy non-smokers in almost symmetrically bilateral fronto-parietal tracts consisting of a major white matter pathway, the superior longitudinal fasciculus (SLF). Conclusion/Significance We found the almost symmetrically bilateral fronto-parietal whiter matter changes in a relatively large sample of chronic smokers. These findings support the hypothesis that chronic cigarette smoking involves alterations of bilateral fronto-parietal connectivity.

Alterations in regional homogeneity of resting-state brain activity in ketamine addicts.

Ketamine is a non-competitive anatognist of the N-methyl-D-aspartate (NMDA) receptor commonly used as an anesthetic and analgesic. In sub-anesthetic doses, it can induce temporary psychotic symptoms and has served as a pharmacological model for schizophrenia. While its acute effects on brain and behavior have been studied, the effects of long-term exposure to ketamine on brain activity have been largely unexplored. In this study, we aimed to examine such effects on spontaneous brain dynamics measure using resting-state functional magnetic resonance imaging (fMRI). Forty-one patients with ketamine dependence and forty-four healthy control subjects were imaged with BOLD fMRI using a 3.0-Tesla Siemens scanner at the Magnetic Resonance Center of Hunan Provincial Peoples Hospital, analyzed with the regional homogeneity (ReHo) method. Compared with healthy controls, decreased ReHo was found in ketamine users in the right anterior cingulate cortex and increased ReHo was found in left precentral frontal gyrus (p<0.05, cluster-level corrected). We also observed negative correlations between increased ReHo in precentral frontal gyrus and estimated total lifetime ketamine consumption and ketamine craving levels. To our knowledge, this is the first study the long-term effects of ketamine exposure on brain functional activity. Our findings indicate that ketamine dependence is associated with alterations in the functional connectivity of medial and lateral prefrontal cortices.

Morphine withdrawal decreases responding reinforced by sucrose self-administration in progressive ratio.

Previous studies have shown that withdrawal from psychostimulant drugs such as d‐amphetamine or methamphetamine decreases motivation to work for a natural reinforcement, which is thought to be associated with the withdrawal‐induced depressive state and hypofunction of the mesolimbic dopamine system. However, to our knowledge, studies exploring the effect of morphine withdrawal on motivation for a natural reinforcement are lacking. The purpose of the present study was to examine whether motivation to work for a natural reinforcement changes during morphine withdrawal. Three groups of male Sprague–Dawley rats were trained to respond on a nose poke for a 4% sucrose solution under a progressive ratio schedule and were subsequently administered a 10‐day regimen of injection of high or low dose of morphine or saline. Their duration of break point and withdrawal symptoms were assessed. The finding showed that break points were significantly reduced on day 1 and persisted to at least day 10 of withdrawal without change in locomotor activity. There were hardly any differences bear mentioning when comparing the magnitude of the decrease between the high‐ and the low‐dose group, whereas the withdrawal scales were significant greater in the high‐dose group than in the low‐dose group. The results suggest that the morphine withdrawal resulted in decreased motivation to obtain the natural reinforcement. The progressive ratio procedure may be a useful technique for evaluation of changes in motivation for natural reinforcing stimuli following withdrawal from opiates.

Altered spontaneous activity in young chronic cigarette smokers revealed by regional homogeneity

BackgroundFew studies have been previously published about the resting state brain activity in young chronic smokers, although many previous fMRI studies have shown that the task-related activity pattern is altered in chronic smokers.MethodsIn the present study, forty-five healthy smokers (age: 27.9 ± 5.6 year) and forty-four healthy non-smoking control subjects (age: 26.3 ± 5.8 year) have been imaged with functional magnetic resonance imaging (fMRI) and analyzed with the regional homogeneity (ReHo) approach.ResultsCompared with healthy controls, decreased ReHo was found in smokers in the right inferior frontal cortex and increased ReHo was found in the left superior parietal lobe (P < 0.01, 35 Voxels,Alphasim corrected).ConclusionsOur data suggested that, during resting state, neural function is less synchronized in the right inferior frontal cortex and more synchronized in the left superior parietal lobe in chronic smokers compared to non-smokers. The decreased synchronization in the right inferior frontal cortex may reflect lacking of control over reward-related behavior, and the increased synchronization may reflect smoking urges.

[miR-126 inhibits colon cancer proliferation and invasion through targeting IRS1, SLC7A5 and TOM1 gene].

OBJECTIVE To explore the expression pattern and function of miR-126 in human colon cancer and the underlying mechanisms. METHODS The expression pattern of miR-126 in high-density human colon cancer tissue microarray was analyzed by in situ hybridization. Further more, the biological function of miR-126 in colon cancer in vitro was investigated by establishing a stable miR-126 over-expression cell lines. RESULT The expression of miR-126 was lower in the tumor tissue, especially in metastasis tissue. The down-regulation of miR-126 was more obvious in the patients who displayed bad prognosis (P=0.025). Over-expression of miR-126 in colon cancer cell was able to inhibit cell proliferation, promote cell apoptosis and reduce the invasive ability. MiR-126 significantly enhanced the sensitivity of the colon cancer cell to chemotherapeutic drug. It has been shown that IRS1, SLC75A and TOM1 were the potential target genes of miR-126 in colon cancer. CONCLUSION MiR-126 was able to inhibit the development of colon cancer and its level was closely related with the prognosis of patients with colon cancer. The potential target genes for miR-126 might include IRS1, SLC7A5 and TOM1. Therefore, miR-126 might be a therapeutic target for colon cancer diagnosis and treatment.