Synthesis of 2,6-diaryl-substituted pyridines and their antitumor activities

For the development of novel antitumor agents, we designed and synthesized 2,6-diaryl-substituted pyridine derivatives bearing three aryl groups, which are the bioisosteres of terpyridine, and evaluated their biological activities. Most of the 18 prepared compounds showed moderate cytotoxicity against several human cancer cell lines. From the structure-activity relationships we may conclude that the number of aryl groups employed would be critical for their biological activities.     

Surface modification of and selective protein attachment to a flexible microarray pattern using atmospheric plasma with a reactive gas

The hydrophobic and hydrophilic properties of the surface of poly-ether sulfone (PES) films were controlled by an atmospheric pressure plasma (AP) treatment using reactive gases (Ar/H₂ and Ar/O₂). The surface properties of the Ar/H₂ and Ar/O₂ in series AP-treated PES films showed higher surface roughness (～120%), surface energy (～30%) and hydrophilic properties (oxygen content ～10%) than the Ar/O₂ AP-treated PES film. The protein staining results confirmed that an activated region on the patterned PES film with high selectivity and sensitivity was well-defined and formed. This method is suitable for fabricating flexible protein adhesive chips with uniform biomolecular adhesive properties.     

Changes of Motor Deactivation Regions in Patients with Intracranial Lesions

Objective

There is a rich literature confirming the default mode network found compatible with task-induced deactivation regions in normal subjects, but few investigations of alterations of the motor deactivation in patients with intracranial lesions. Therefore, we hypothesized that an intracranial lesion results in abnormal changes in a task-induced deactivation region compared with default mode network, and these changes are associated with specific attributes of allocated regions.

Methods

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) during a motor task were obtained from 27 intracranial lesion patients (mean age, 57.3 years; range 15-78 years) who had various kinds of brain tumors. The BOLD fMRI data for each patient were evaluated to obtain activation or deactivation regions. The distinctive deactivation regions from intracranial lesion patients were evaluated by comparing to the literature reports.

Results

There were additive deactivated regions according to intracranial lesions: fusiform gyrus in cavernous hemangioma; lateral occipital gyrus in meningioma; crus cerebri in hemangiopericytoma; globus pallidus, lateral occipital gyrus, caudate nucleus, fusiform gyrus, lingual gyrus, claustrum, substantia nigra, subthalamic nucleus in GBM; fusiform gyrus in metastatic brain tumors.

Conclusion

There is increasing interest in human brain function using fMRI. The authors report the brain function migrations and changes that occur in patients with intracranial lesions.     

Free Hand Insertion Technique of S2 Sacral Alar-Iliac Screws for Spino-Pelvic Fixation: Technical Note,Acadaveric Study

A rigid spino-pelvic fixation to anchor long constructs is crucial to maintain the stability of long fusion in spinal deformity surgery. Besides obtaining immediate stability and proper biomechanical strength of constructs, the S2 alar-iliac (S2AI) screws have some more advantages. Four Korean fresh-frozen human cadavers were procured. Free hand S2AI screw placement is performed using anatomic landmarks. The starting point of the S2AI screw is located at the midpoint between the S1 and S2 foramen and 2 mm medial to the lateral sacral crest. Gearshift was advanced from the desired starting point toward the sacro-iliac joint directing approximately 20° angulation caudally in sagittal plane and 30° angulation horizontally in the coronal plane connecting the posterior superior iliac spine (PSIS). We made a S2AI screw trajectory through the cancellous channel using the gearshift. We measured caudal angle in the sagittal plane and horizontal angle in the coronal plane. A total of eight S2AI screws were inserted in four cadavers. All screws inserted into the iliac crest were evaluated by C-arm and naked eye examination by two spine surgeons. Among 8 S2AI screws, all screws were accurately placed (100%). The average caudal angle in the sagittal plane was 17.3±5.4°. The average horizontal angle in the coronal plane connecting the PSIS was 32.0±1.8°. The placement of S2AI screws using the free hand technique without any radiographic guidance appears to an acceptable method of insertion without more radiation or time consuming.     

Aza-analogue of mevinolin: Synthesis of substituted octahydroisoquinoline,the bottom half of aza-analogue of mevinolin

trans-Ethyl 1,2,3,4a,5,6,8a-octahydro-2-benzyl-4-hydroxy-6-methyl-5- isoquinoline-carboxylate was prepared by intramolecular Diels-Alder reaction as a precursor of newly designed aza-analogue of mevinolin.     

Synthesis and biological activity of indazole-derived HMG-CoA reductase inhibitors

New hypolipaemic agents, in which substituted indazole nucleus is connected to tetrahydro-4-hydroxy-2H-pyran-2-one by a two-carbon bridge, were designed and synthesized to show significant inhibitory activity against microsomal HMG-CoA reductase in rat liver.     

Synthesis and biological activity of 4,5-polymethylenepyrazole-derived HMG-COA reductase inhibitors

New HMG-CoA reductase inhibitors, in which 3-substituted 4,5-polymethylenepyrazoles are employed as a hydrophobic anchor connected to tetrahydro-4-hydroxy-2H-pyran-2-one by a two-carbon bridge, were designed and synthesized to exhibit significant inhibitory activity comparable to mevinolin. The most potent enzyme inhibitor (11cc, IC₅₀=0.01 μM) is 4-fold more potent than lovastatin.     

Role of neuropeptide Y and proopiomelanocortin in fluoxetine-induced anorexia

Fluoxetine is an anorexic agent known to reduce food intake and weight gain. However, the molecular mechanism by which fluoxetine induces anorexia has not been well-established. We examined mRNA expression levels of neuropeptide Y (NPY) and proopiomelanocortin (POMC) in the brain regions of rats using RT-PCR and in situ hybridization techniques after 2 weeks of administering fluoxetine daily. Fluoxetine persistently suppressed food intake and weight gain during the experimental period. The pair-fed group confirmed that the reduction in body weight in the fluoxetine treated rats resulted primarily from decreased food intake. RT-PCR analyses showed that mRNA expression levels of both NPY and POMC were markedly reduced by fluoxetine treatment in all parts of the brain examined, including the hypothalamus. POMC mRNA in situ signals were significantly decreased, NPY levels tended to increase in the arcuate nucleus (ARC) of fluoxetine treated rats (compared to the vehicle controls). In the pair-fed group, NPY mRNA levels did not change, but the POMC levels decreased (compared with the vehicle controls). These results reveal that the chronic administration of fluoxetine decreases expression levels in both NPY and POMC in the brain, and suggests that fluoxetine-induced anorexia may not be mediated by changes in the ARC expression of either NPY or POMC. It is possible that a fluoxetine raised level of 5-HT play an inhibitory role in the orectic action caused by a reduced expression of ARC POMC (alpha-MSH).