Cyclopiazonic acid增加SHR和WKY血管平滑肌细胞Ca~(2+)-依赖性外向K~+-电流

采用全细胞及细胞贴附式斑片钳技术记录自发性高血压大鼠(SHR)和Wistar-Kyoto对照鼠(WKY)培养主动脉平滑肌细胞的Ca~(2+)-依赖性外向K~+电流[I_(k(Ca))],测定肌浆网Ca~(2+)泵抑制剂CPA对其影响.CPA能增加I_K(Ca))单通道开放时间,缩短关闭时间,增加全细胞I_(K(Ca))幅度,这些作用与Ca~(2+)相关并可被K~+通道阻断药glybenclamide阻断。CPA作用在SHR和WKY之间无明显差异。结果提示高血压状态下血管平滑肌的功能改变可能与I_(K(Ca))无关。     

Paradoxical hormonal and behavioral responses to hypothyroid and hyperthyroid states in the Wistar-Kyoto rat.

Wistar-Kyoto (WKY) rats show endogenous depressive behavior that can be reversed by antidepressants. Given that WKYs exhibit decreased sensitivity to some antidepressants and treatment-resistant depressed patients often show hypothalamic-pituitary-thyroid (HPT) dysregulation, we examined the behavioral and HPT hormonal responses of WKYs to altered thyroid status. "Euthyroid" WKYs had elevated basal plasma TSH and T(3) levels as compared to Wistars. Hypothyroidism increased TSH levels more in WKYs than in Wistars and increased response latency in the open field test (OFT) of WKYs only. Administration of T(4) and T(3) suppressed plasma TSH equally in both strains. Wistars responded to increased T(3) levels with decreased response latency and increased activity in the OFT, but increased immobility in the forced swim test. In contrast, WKYs responded only to the high T(3) levels with decreased response latency in the OFT. These results suggest the existence of a decreased central nervous system sensitivity to thyroid hormones in WKYs that could be related to their depressive behavior.     

Objective and subjective evaluation of adaptive speech enhancement methods for functional MRI

Purpose:

To recover speech corrupted by functional magnetic resonance imaging (fMRI) acoustic noise using two‐channel adaptive speech enhancement techniques.

Materials and Methods:

Speech corrupted by noise generated from a 3 T MRI scanner was recorded using diffuse‐field microphones and a data acquisition board. Multiband and subband adaptive speech enhancement methods are used to recover the speech signal from the recordings. Normalized least mean squares (NLMS) algorithm was used for updating the filter coefficients in each band.

Results:

The methods are successful in enhancing the speech quality. They are successful in improving the convergence rate of the adaptive filter. Multiband and subband methods have a similar performance in terms of noise reduction and in the subjective tests. The subband method introduces less speech distortion compared to the multiband method. The subband method requires a lower number of computations per sample.

Conclusion:

Adaptive speech enhancement techniques are effective in reducing fMRI background noise in the recordings. Based on the analysis, we conclude that subband‐based methods are more suited for enhancing speech corrupted by fMRI noise. J. Magn. Reson. Imaging 2010;31:46–55. © 2009 Wiley‐Liss, Inc.     

9The TANTALUSTM System for obesity: effect on gastric emptying of solids

Background: Gastric electrical stimulation (GES) is currently investigated for the treatment of obesity. The TANTALUS System delivers gastric contractility modulation (GCM) signals in synchrony with gastric slow waves, resulting in significant augmentation of gastric contractions during food intake. We hypothesized that such modulation of contractile activity may affect gastric emptying and plasma ghrelin levels. Aim: To test the effect of GCM of the gastric antrum on gastric emptying of solids and ghrelin levels. Methods: 12 obese subjects were implanted with 2 pairs of antral electrodes and an implantable pulse generator (IPG, TANTALUS ^TM) Gastric emptying test (GE) for solids was performed twice, on separate days, in each subject, starting few weeks after implantation: 1) control, before the start of stimulation, and 2) with stimulation, after device was turned on. Blood samples for ghrelin, were taken at baseline, and at 15, 30, 60 and 120 min after the test meal. Results as mean + SD, analysis by t‐test and p < 0.05. Results: 11 females, 1 male, age: 39.1 ± 8.9 years, BMI: 41.6 ± 3.4, 3 subjects with type 2 diabetes. One diabetic patient did not complete GE test because of technical issues. GCM significantly accelerated gastric emptying: retention at 2 hours 18.7 ± 12.2% vs. 31.9 ± 16.4%, stimulation vs. control respectively, p = 0.008. T ^1/2 78.3 ± 23.5 vs. 95 ± 31.7 min, stimulation vs. control respectively, p = 0.04. Mean results for gastric emptying were within normal at both baseline and stimulation. Meal ingestion induced only minimal, insignificant reduction in ghrelin levels. There was no significant difference in AUC of ghrelin between control and stimulation. Conclusions: After GCM stimulation, there is significant acceleration of gastric emptying of solids in obese patients, without affect on ghrelin levels. The obese subjects did not exhibit the significant, meal‐induced reduction in ghrelin.      

Evaluation of postpartum blood loss after misoprostol-induced labour

Objective  To objectively evaluate postpartum blood loss after successful misoprostol induction and compare it with blood loss after oxytocin induction of labour.
Design  Prospective randomised study.
Setting  Labour ward in university maternity hospital.
Population  A total of 150 women up to third parity with completed 40 weeks of singleton normal pregnancy, average size cephalic fetus.
Methods  Cases were randomised between oxytocin induction and misoprostol induction. Blood was collected in suction set and measured in the delivery room starting after delivery of the fetus and was evaluated by pad weighing in the following 6 hours. Pre- and postdelivery haematocrit were measured and difference between the two values was assessed and analysed.
Main outcome measures  Success of induction, induction delivery interval, postpartum blood loss, and difference between pre- and postdelivery haematocrit.
Results  Induced labour was significantly faster with misoprostol induction ( P < 0.001). Blood loss and haematocrit difference was significantly greater in the misoprostol group than in oxytocin group ( P < 0.02 and 0.001, respectively). Blood loss in both groups was significantly correlated with higher initial Bishop score ( P < 0.001 and 0.024, respectively) and short labour duration ( P < 0.0002 and 0.0001, respectively).
Conclusions  Misoprostol induction is associated with increased blood loss especially when used in women with high Bishop score; therefore, it is better reserved for cases requiring cervical ripening.     

Is MSH2 a breast cancer susceptibility gene?

Mutations in the DNA mismatch repair gene MSH2 lead to increased replication error and microsatellite instability and account for a substantial proportion of hereditary non-polyposis colorectal cancer (Lynch syndrome). A recent international collaborative genome-wide linkage scan (GWS) for breast cancer susceptibility loci found some evidence for there being a breast cancer susceptibility gene in a genomic region on chromosome 2p close to MSH2. We sought to investigate the possibility that mutations in MSH2 might explain the multiple cases of breast cancer in some families that were included in the international GWS. DNA samples from the affected probands of 59 multiple-case breast cancer families, many of whom gave LOD scores >0.5 in the MSH2 region, were screened for large genomic alterations in MSH2 via the Multiplex Ligation-dependant Probe Amplification (MLPA) assay and for coding region mutations via exonic sequencing. Several of the families also contained cases of colorectal cancer in addition to breast cancer and had been included in the GWS that had identified a positive LOD score on chromosome 2p. Using MLPA, c.1236C > T was identified in one proband but this variant was not predicted to create an alternate acceptor/donor site within exon 7 MSH2 using in silico analyses. A c.1734T > C was identified in a second proband via exonic sequencing but testing of the variant in other family members did not support segregation of this variant with disease. Extensive screening of 59 multiple-case breast cancer families did not identify any coding region mutations or larger genomic alterations in MSH2 that might implicate MSH2 as a breast cancer susceptibility gene.