BACKGROUND/AIMS: Patients with irritable bowel syndrome (IBS) are characterized by abnormal central processing with altered brain activation in response to visceral nociceptive signals. The effect of electroacupuncture (EA) on IBS patients is unclear. The study is set to study the effect of EA on brain activation during noxious rectal distension in IBS patients using a randomized sham-controlled model. METHODS: Thirty IBS-diarrhea patients were randomized to true electroacupuncture or sham acupuncture. Functional MRI was performed to evaluate cerebral activation at the following time points: (1) baseline when there was rectal distension only, (2) rectal distension during application of EA, (3) rectal distension after cessation of EA and (4) EA alone with no rectal distension. Group comparison was made under each condition using SPM5 program. RESULTS: Rectal distension induced significant activation of the anterior cingulated cortex, prefrontal cortex, thalamus, temporal regions and cerebellum at baseline. During and immediately after EA, increased cerebral activation from baseline was observed in the anterior cingulated cortex, bilateral prefrontal cortex, thalamus, temporal regions and right insula in both groups. However, true electroacupuncture led to significantly higher activation at right insula, as well as pulvinar and medial nucleus of the thalamus when compared to sham acupuncture. CONCLUSIONS: We postulate that acupuncture might have the potential effect of pain modulation in IBS by 2 actions: (1) modulation of serotonin pathway at insula and (2) modulation of mood and affection in higher cortical center via ascending pathway at the pulvinar and medial nucleus of the thalamus.
Acupuncture ; Acupuncture Therapy ; Brain ; Cerebellum ; Electroacupuncture ; Humans ; Irritable Bowel Syndrome ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Magnetics ; Magnets ; Neural Pathways ; Pain Perception ; Prefrontal Cortex ; Pulvinar ; Salicylamides ; Serotonin ; Thalamus

AIMTo investigate the effect of DAPT (gamma-secretase inhibitor) on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma.

METHODOLOGYHuman tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence (IF) were employed to determine the intracellular expression levels.

RESULTSDAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split-1 (Hes-1), a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells.

CONCLUSIONDAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch-1 and Caspase-3.

Amyloid Precursor Protein Secretases ; antagonists & inhibitors ; Antineoplastic Agents ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Basic Helix-Loop-Helix Transcription Factors ; drug effects ; Carcinoma ; pathology ; Caspase 3 ; drug effects ; Cell Line, Tumor ; Cell Membrane ; drug effects ; Cell Nucleus ; drug effects ; Cyclin D1 ; drug effects ; Dipeptides ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; G1 Phase ; drug effects ; Homeodomain Proteins ; drug effects ; Humans ; Receptor, Notch1 ; drug effects ; Repressor Proteins ; drug effects ; Resting Phase, Cell Cycle ; drug effects ; Tongue Neoplasms ; pathology ; Transcription Factor HES-1