Insula-specific responses induced by dental pain: a proton magnetic resonance spectroscopy study

OBJECTIVES: To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. METHODS: Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. RESULTS: Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. CONCLUSION: The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed

Ethanol-Mediated Regulation of Cytochrome P450 2A6 Expression in Monocytes: Role of Oxidative Stress-Mediated PKC/MEK/Nrf2 Pathway

Cytochrome P450 2A6 (CYP2A6) is known to metabolize nicotine, the major constituent of tobacco, leading to the production of toxic metabolites and induction of oxidative stress that result in liver damage and lung cancer. Recently, we have shown that CYP2A6 is induced by ethanol and metabolizes nicotine into cotinine and other metabolites leading to generation of reactive oxygen species (ROS) in U937 monocytes. However, the mechanism by which CYP2A6 is induced by ethanol is unknown. In this study, we have examined the role of the PKC/Nrf2 pathway (protein kinase C-mediated phosphorylation and translocation of nuclear erythroid 2-related factor 2 to the nucleus) in ethanol-mediated CYP2A6 induction. Our results showed that 100 mM ethanol significantly induced CYP2A6 mRNA and protein (∼150%) and increased ROS formation, and induction of gene expression and ROS were both completely blocked by treatment with either a CYP2E1 inhibitor (diallyl sulfide) or an antioxidant (vitamin C). The results suggest the role of oxidative stress in the regulation of CYP2A6 expression. Subsequently, we investigated the role of Nrf2 pathway in oxidative stress-mediated regulation of CYP2A6 expression in U937 monocytes. Our results showed that butylated hydroxyanisole, a stabilizer of nuclear Nrf2, increased CYP2A6 levels >200%. Staurosporine, an inhibitor of PKC, completely abolished ethanol-induced CYP2A6 expression. Furthermore, our results showed that a specific inhibitor of mitogen-activated protein kinase kinase (MEK) (U0126) completely abolished ethanol-mediated CYP2A6 induction and Nrf2 translocation. Overall, these results suggest that CYP2E1-mediated oxidative stress produced as a result of ethanol metabolism translocates Nrf2 into the nucleus through PKC/MEK pathway, resulting in the induction of CYP2A6 in monocytes. An increased level of CYP2A6 in monocytes is expected to further increase oxidative stress in smokers through CYP2A6-mediated nicotine metabolism. Thus, this study has clinical relevance because of the high incidence of alcohol use among smokers, especially in HIV-infected individuals

In vivo phosphorus 31 magnetic resonance spectroscopy of human uveal melanomas and other intraocular tumors

We studied the feasibility of using the surface coil probe technique for the noninvasive in vivo study of ocular tumors by phosphorus 31 magnetic resonance spectroscopy. The characteristic organophosphate metabolites of suspected uveal melanomas before proton beam irradiation were determined qualitatively by phosphorus 31 magnetic resonance spectroscopy in vivo using a three-turn surface coil. Spectra of choroidal hemangioma, osteoma, and metastasis were also obtained in vivo and compared with those of uveal melanomas. Analysis of spectra performed at 1.5 T showed significant peaks of phosphomonoesters, inorganic phosphate, phosphodiesters, phosphocreatine, and adenosine 5'-triphosphates. The unusually high concentration of phosphodiesters may be considered as a marker for uveal melanomas and other choroidal tumors. By analyzing the ratio of phosphocreatine to phosphodiesters spectral area values, we interpreted qualitatively spectra of intraocular tumors to differentiate malignant tumors from benign lesions. Nevertheless, the main limitation of interpreting the spectra was their contamination by signals from surrounding tissues

An evaluation of telemedicine in surgery: telediagnosis compared with direct diagnosis

HYPOTHESIS: Telemedicine for real-time transmission of clinical documents and interactive remote telediagnosis allows accurate clinical application in surgery. DESIGN: Prospective cohort study in which 2 hospitals, 120 miles apart, were connected via integrated services digital network (ISDN) teleconferencing units, and each evaluated clinical cases in real time. SETTING: A tertiary care university hospital and primary care county hospital. PARTICIPANTS: Between May 1, 1998, and June 30, 1998, 112 patients undergoing digestive or endocrine surgery were evaluated by teletransmission (study group) and direct vision (control group). Diagnosis had to be known by the viewer, and either conventional magnetic resonance imaging or computed tomographic scans were available. MAIN OUTCOME MEASURES: Picture quality, organ structure, and pathologic finding viewed on telemedicine documents were evaluated by radiologists and surgeons blind to diagnosis. Accuracy of remote 128-kilobit (kb)/s transmission-rate diagnoses and results were compared with those obtained directly. RESULTS: Picture quality was "good" or "excellent" in 92.9% of transmitted documents and 95.5% of live images (P>.4). The target organ was always recognized, structure and pathologic finding were analyzable in 98.2% of transmitted documents and 99.1% of live documents, and fine structures were assessable in 89.3% of transmitted pictures and 95.5% of live pictures (P>.05). Diagnosis was made in 84.8% of transmitted cases and 93.8% of live cases (P = .02). CONCLUSIONS: Low bandwidth (128 kb/s) telemedicine application in surgery is reliable in evaluating remote cases. Loss of image quality through teletransmission occurred in 2.7% of cases, and diagnosis was not possible in 15.2% of transmitted vs 6.2% of live cases, suggesting factors other than technical quality (choice of radiological studies, additional clinical information required, etc). This underscores the importance of real-time interactive discussion during surgical teleconferences

Aperistaltic effect of hyoscine N-butylbromide versus glucagon on the small bowel assessed by magnetic resonance imaging

The aim of this prospective study was to compare the intraindividual aperistaltic effect of 40 mg hyoscine N-butylbromide (HBB/Buscopan) with that of 1 mg glucagon on small bowel motility by using magnetic resonance imaging (MRI). Ten healthy volunteers underwent two separate 1.5-T MRI studies (HBB/glucagon) after a standardized oral preparation with an aqueous solution of Gd-DOTA and ispaghula (Metamucil). A 2D T1-w GRE sequence was acquired (TR 2.7 ms/TE 1.3 ms, temporal resolution 0.25 s) before and after intravenous (i.v.) drug administration and motility was followed over 1 h. On the resulting images the cross-sectional luminal diameters were assessed and plotted over time. Baseline motility frequency, onset of aperistalsis, duration of arrest, reappearance of motility and return to normal motility were analysed. Significant differences regarding reliability and duration of aperistalsis were observed. In the HBB group aperistalsis lasted a mean of 6.8 +/- 5.3 min compared with 18.3 +/- 7 min after glucagon (p < 0.0001). In 50% of cases HBB did not accomplish aperistalsis, whereas glucagon always succeeded (p = 0.05). There were no significant differences in terms of baseline and end frequencies for the onset of aperistalsis (22.2 +/- 37.5 s HBB/13.4 +/- 9.2 s glucagon, p = 0.1), nor for the return to normal motility. Arrest of small bowel motion is achieved more reliably and lasts significantly longer after i.v. administration of 1 mg glucagon compared with 40 mg HBB

Novel Phosphoinositides in Barley Aleurone Cells (Additional Evidence for the Presence of Phosphatidyl-scyllo-Inositol).

A novel isomer of phosphatidylinositol that differs in the structure of the head group was detected in barley (Hordeum vulgare cv Himalaya) seeds. In this paper we describe our efforts to elucidate the structure of the novel isomer. Evidence from a variety of techniques, including chemical modification of in vivo 32Pi- and myo-[3H]inositol-labeled compounds, gas chromatography-mass spectrometry analysis, in vivo incorporation of scyllo-[3H]inositol, and enzymatic studies that suggest that the structure is phosphatidylscyllo-inositol (scyllo-PI), is presented. The use of microwave energy to significantly enhance the slow rate of hydrolysis of phosphoinositides is described. The presence of scyllo-PI can be easily overlooked by the methods commonly employed; therefore, experimental considerations important for the detection of scyllo-PI are discussed