Comparison of relative forced expiratory volume of one second with dynamic magnetic resonance imaging parameters in healthy subjects and patients with lung cancer

PURPOSE: To assess relative forced expiratory volume in one second (FEV1/vital capacity (VC)) in healthy subjects and patients with a lung tumor using dynamic magnetic resonance imaging (dMRI) parameters. MATERIALS AND METHODS: In 15 healthy volunteers and 31 patients with a non-small-cell lung carcinoma stage I (NSCLC I), diaphragmatic length change (LE1) and craniocaudal (CC) intrathoracic distance change within one second from maximal inspiration (DE1) were divided by total length change (LE(total), DE(total)) as a surrogate of spirometric FEV1/VC using a true fast imaging with steady-state precession (trueFISP) sequence (TE/TR = 1.7/37.3 msec, temporal resolution = 3 images/second). Influence of tumor localization was examined. RESULTS: In healthy volunteers FEV1/VC showed a highly significant correlation with LE1/LE(total) and DE1/DE(total) (r > 0.9, P < 0.01). In stage IB tumor patients, comparing tumor-bearing with the non-tumor-bearing hemithorax, there was a significant difference in tumors of the middle (LE1/LE(total) = 0.63 +/- 0.05 vs. 0.73 +/- 0.04, DE1/DE(total) = 0.66 +/- 0.05 vs. 0.72 +/- 0.04; P < 0.05) and lower (P < 0.05) lung region. Stage IA tumor patients showed no significant differences with regard to healthy subjects. CONCLUSION: dMRI is a simple noninvasive method to locally determine LE1/LE(total) and DE1/DE(total) as a surrogate of FEV1/VC in volunteers and patients. Tumors of the middle and lower lung regions have a significant influence on these MRI parameters.     

WIN 55,212-2 decreases the spatial spread of neocortical excitation in vitro

The 'intrinsic optical signal' was used to monitor neuronal network excitability. The cannabinoid receptor type 1 agonist WIN 55,212-2 reduced the intensity and the spatial spread of the intrinsic optical signal and prolonged its kinetics in the rat neocortex in vitro. These effects were antagonized by the cannabinoid receptor antagonist SR141716A. Thus, our results suggest that neocortical network activity is modulated via the activation of cannabinoid receptors. The decrease of neocortical network excitability in the present study is probably due to a decreased excitability of glutamatergic neurons.     

Temporary inactivation of the rostral perirhinal cortex induces an anxiolytic-like effect on the elevated plus-maze and on the yohimbine-enhanced startle response

The present study investigated whether the rostral perirhinal cortex is involved in aversive information processing, particularly in unconditioned fear (anxiety). We temporarily inactivated the rostral perirhinal cortex by local injections of the GABA(A) agonist muscimol (0.0, 1.1, and 4.4 nmol/0.5 microl) and tested whether these injections affected the behavior of rats in the elevated plus-maze and in the yohimbine-enhanced startle test. Temporary inactivation of the rostral perirhinal cortex increased the number of open arm entries and the open arm ratio in the elevated plus-maze. In addition, startle response enhancement caused by the anxiogenic drug yohimbine was reduced by perirhinal cortex inactivation. Taken together, these data clearly show that the rostral perirhinal cortex is involved in the processing of emotional stimuli and is critical for the expression of unconditioned fear (anxiety).     

Differential effects of N-peptidyl-O-acyl hydroxylamines on dynorphin-induced antinociception in the mouse capsaicin test

In the capsaicin test, intrathecal (i.t.) dynorphins are antinociceptive. Cysteine protease inhibitors such as p-hydroxymercuribenzoate (PHMB) given i.t. augment and prolong their activity. The effect of two novel cysteine protease inhibitors, N-peptidyl-O-acyl hydroxylamines, on the antinociception induced by i.t. administered dynorphin A or dynorphin B has been investigated. When administered i.t. 5 min before the injection of capsaicin (800 ng) into the plantar surface of the hindpaw, dynorphin A (62.5-1000 pmol) or dynorphin B (0.5-4 nmol) produced a dose-dependent and significant antinociceptive effect. The effect of dynorphin A (1 nmol) and dynorphin B (4 nmol) disappeared completely within 180 and 60 min, respectively. PHMB (2 nmol) and Boc-Tyr-Gly-NHO-Bz (BYG-Bz) (2 nmol) co-administered with dynorphin A or dynorphin B significantly prolonged antinociception induced by both. On the other hand, Z-Phe-Phe-NHO-Bz (ZFF-Bz) (1 and 2 nmol) only prolonged antinociception induced by dynorphin A. The results suggest that Z-Phe-Phe-NHO-Bz is an inhibitor of cysteine proteases preferring cleavage of dynorphin A, with less specificity towards dynorphin B in the mouse spinal cord.     

Association of peroxisome proliferator-activated receptor gamma 2 Pro-12-Ala polymorphism with endometriosis

We explored the association of the PPAR-gamma2 (peroxisome proliferator-activated receptor) Pro-12-Ala polymorphism with endometriosis in a case-control study with 51 women with endometriosis stages I-IV and 55 control women without endometriosis. The 12-Pro allele of PPAR-gamma2 may have protective effects avoiding the development and progression of endometriosis.     

Time-resolved contrast-enhanced three-dimensional pulmonary MR-angiography: 1.0 M gadobutrol vs. 0.5 M gadopentetate dimeglumine

PURPOSE: To compare contrast characteristics and image quality of 1.0 M gadobutrol with 0.5 M Gd-DTPA for time-resolved three-dimensional pulmonary magnetic resonance angiography (MRA). MATERIALS AND METHODS: Thirty-one patients and five healthy volunteers were examined with a contrast-enhanced time-resolved pulmonary MRA protocol (fast low-angle shot [FLASH] three-dimensional, TR/TE = 2.2/1.0 msec, flip angle: 25 degrees, scan time per three-dimensional data set = 5.6 seconds). Patients were randomized to receive either 0.1 mmol/kg body weight (bw) or 0.2 mmol/kg bw gadobutrol, or 0.2 mmol/kg bw Gd-DTPA. Volunteers were examined three times, twice with 0.2 mmol/kg bw gadobutrol using two different flip angles and once with 0.2 mmol/kg bw Gd-DTPA. All contrast injections were performed at a rate of 5 mL/second. Image analysis included signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements in lung arteries and veins, as well as a subjective analysis of image quality. RESULTS: In patients, significantly higher SNR and CNR were observed with Gd-DTPA compared to both doses of gadobutrol (SNR: 35-42 vs.17-25; CNR 33-39 vs. 16-23; P < or = 0.05). No relevant differences were observed between 0.1 mmol/kg bw and 0.2 mmol/kg bw gadobutrol. In volunteers, gadobutrol and Gd-DTPA achieved similar SNR and CNR. A significantly higher SNR and CNR was observed for gadobutrol-enhanced MRA with an increased flip angle of 40 degrees. Image quality was rated equal for both contrast agents. CONCLUSION: No relevant advantages of 1.0 M gadobutrol over 0.5 M Gd-DTPA were observed for time-resolved pulmonary MRA in this study. Potential explanations are T2/T2*-effects caused by the high intravascular concentration when using high injection rates.     

Isoflurane reduces glutamatergic transmission in neurons in the spinal cord superficial dorsal horn: evidence for a presynaptic site of an analgesic action

The minimum alveolar concentration (MAC) of a volatile anesthetic defines anesthetic potency in terms of a suppressed motor response to a noxious stimulus. Therefore, the MAC of an anesthetic might in part reflect depression of motor neuron excitability. In the present study we evaluated the effect of isoflurane (ISO) on neurons in the substantia gelatinosa driven synaptically by putative nociceptive inputs in an in vitro spinal cord preparation of the rat. Whole-cell patch-clamp recordings were performed in neurons with their soma in the substantia gelatinosa of transverse rat spinal cord slices. We investigated the effect of ISO on excitatory postsynaptic currents (EPSC) evoked by dorsal root stimulation (eEPSC), spontaneous (sEPSC), and miniature (mEPSC) EPSC. ISO reversibly reduced the amplitude of eEPSC to 39% +/- 22% versus control. ISO decreased the frequency of sEPSC and mEPSC to 39% +/- 26% and 63% +/- 7%. Neither the amplitudes nor the kinetics of mEPSC and sEPSC were altered by ISO. We conclude that ISO depresses glutamatergic synaptic transmission of putative nociceptive primary-afferent inputs, presumably by reducing the release of the excitatory transmitter. This effect may contribute to an antinociceptive action of volatile anesthetics at the spinal cord level. IMPLICATIONS: The present electrophysiological in vitro experiments provide evidence that the volatile anesthetic isoflurane reduces excitatory transmitter release at the first site of synaptic integration of nociceptive inputs, the spinal cord superficial dorsal horn. This effect may contribute to the anesthetic action of volatile anesthetics at the spinal cord level.