Cortico-striato-thalamo-cortical circuit abnormalities in obsessive-compulsive disorder: A voxel-based morphometric and fMRI study of the whole brain.

The primary aim of this study was to identify structural and functional abnormalities in the brains of obsessive-compulsive disorder (OCD) patients. Another aim was to assess the effect of serotonin selective reuptake inhibitors (SSRIs) on brain structure of OCD patients. All subjects underwent brain magnetic resonance imaging (MRI) and resting functional MRI (fMRI). High-resolution three-dimensional images were processed using the voxel-based morphometry (VBM) method. The final analysis included 18 OCD patients and 16 healthy controls. In the OCD patients there was a decrease in gray matter volume in the bilateral cingulate cortex and bilateral striatum. In some cortical structures including the cerebellar anterior lobe, left orbital frontal gyrus, right middle frontal gyrus, left middle temporal gyrus, precentral gyrus, and postcentral gyrus, there was an increase in gray matter volume. On fMRI the OCD patients had overactivation of the right cerebellum and right parietal lobe and reduced activation of the left cingulate gyrus, putamen, and caudate nucleus. Eleven OCD patients who improved during 12 weeks of drug treatment with sertraline hydrochloride had a significant increase in gray matter volume in several brain structures but no significant differences were found on resting fMRI. The results indicated a consistent trend between structural and functional images. Higher cortical structures showed increased gray matter volume and increased activation as did the cerebellum whereas subcortical structures showed decreased gray matter volume and decreased activation. And brain structure improvement consisted with symptom improvement after SSRIs treatment in OCD patients.

Computer aided screening of potent inhibitor compounds against inhibitor resistant TEM ß-lactamase mutants from traditional Chinese medicine.

Inhibitor-resistant TEM (IRT) type ß-lactamase mutation is largely known. Therefore, it is of interest to identify new yet improved leads against IRT from traditional Chinese medicine. Hence, we screened more than 10,000 compounds from Chinese medicine (tcm@taiwan database) with mutant molecular IRT models through docking techniques. This exercise identified compounds affeic acid, curcumin, salvianolic acid E, ferulic acid and p-coumaric acid with high binding score with the mutants. This was further validated in vitro where salvianolic acid E combined with cefoperazone and sulbactam effectively inhibit the R244S mutant.

Synthesis and potential anticonvulsant activity of new N-3-substituted 5,5-cyclopropanespirohydantoins.

Thirteen new 5-cyclopropanespirohydantoins with various N-3 substituents were synthesized and their pharmacological activity was determined with the objective to better understand their structure-activity relationship (SAR) for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by maximal electroshock seizure (MES) test and subcutaneous pentylenetetrazole (scPTZ) test models in mice. All compounds substituted with cyclopropyl group at fifth position of hydantoin ring showed better protection against MES test. Compounds 5b, 5d, 5e, 5g and 5j were found to be the most potent compounds of this series and compared with the reference drug phenytoin sodium in MES test. Compound 5j also showed equipotent activity with the standard drug sodium valproate at the doses of 20 and 40 mg kg(-1) in scPTZ test.

[Effects of polyporus polysaccharide on activity and mRNA expression of inducible nitric oxide synthase in peritoneal macrophages of mice].

OBJECTIVE: To study the mechanisms of the antitumor and immunoregulation functions of polyporus polysaccharide (PPS). METHODS: The production of nitric oxide (NO), the activity and mRNA expression of inducible nitric oxide synthase (iNOS) in peritoneal macrophages of mice administered with different dose of PPS were observed by Griess reaction, fluorimetry assay and RT-PCR, respectively. RESULTS: PPS could elevate the iNOS activity with dose-dependence and stimulate the iNOS mRNA expression of peritoneal macrophages in mice. CONCLUSION: The regulation of PPS on the production of NO in peritoneal macrophages of mice may occur at transcriptional level of iNOS. This indicates that the mechanism of PPS's antitumor and immunoregulation functions may be related to increasing NO output of macrophages through stimulating iNOS's denovo synthesis.