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11.
12.
Correlation between 5-HT7 receptor affinity and protection against sound-induced seizures in DBA/2J mice 总被引:2,自引:0,他引:2
Anne Bourson Véronique Kapps Catherine Zwingelstein Alain Rudler Frank G. Boess A. J. Sleight 《Naunyn-Schmiedeberg's archives of pharmacology》1997,356(6):820-826
Audiogenic seizures can be induced in DBA/2J mice following intense auditory stimulation. A number of neurotransmitters, including
5-hydroxytryptamine (5-HT), are believed to be involved in mediating this effect since it has been shown previously that depletion
of 5-HT or blockade of 5-HT receptors protects DBA/2J mice from these audiogenic seizures. The present study was undertaken
to determine whether antagonism of the newly identified 5-HT7 receptor may protect DBA/2J mice from audiogenic seizures by attempting to correlate in vivo potency of compounds with their
affinity at the 5-HT7 receptor. All compounds used in the correlation were shown to be antagonists at the 5-HT7 receptor and a statistically significant correlation was observed between 5-HT7 affinity and doses for half-maximal response (ED50) for protection of DBA/2J mice from sound-induced seizures (r = 0.80; P < 0.05). No significant correlation was observed between in vivo activity and affinity at either 5-HT1A, 5-HT2A or 5-HT2C receptors. It is also unlikely that interactions between the 5-ht5 receptor will protect DBA/2J mice from audiogenic seizures since metergoline and mesulergine which are both active in this
in vivo model have no affinity for the 5-ht5 receptor. There are similarities between the pharmacology of the 5-HT7 receptor and that of the 5-HT1A receptor, however the correlation between the in vivo potency in DBA/2J mice and 5-HT1A affinity was not significant. Furthermore, the 5-HT1A receptor antagonist WAY 100135 did not protect DBA/2J mice from audiogenic seizures at doses that antagonise 5-HT1A receptor-mediated effects in mice. These data suggest that antagonism of 5-HT7 receptors may protect against audiogenic seizures in DBA/2J mice although a definitive conclusion must await studies with
selective 5-HT7 antagonists.
Received: 20 March 1997 / Accepted: 10 August 1997 相似文献
13.
Chretien Marie Francoise; Lebouvier Brigitte; Denis Alain; Chappard Daniel 《Human reproduction (Oxford, England)》1998,13(10):2767-2771
A cytomorphometric analysis of superficial vaginal cells inwomen in three groups of different types of hormonal concentrationwas made. There were 15 women in each group. Group I was studiedduring a natural cycle, group II under oral contraceptive therapyand group III during an in-vitro fertilization (IVF) stimulationprotocol. Morphometric parameters were measured on an imageanalyser. The area, perimeter and several form factors weremeasured separately for nuclei and cytoplasm. The nucleus:cytoplasmicratio was also determined. The cytoplasmic area was significantlyreduced in group II and was associated with a statisticallysignificant reduction of the nuclear area. The nucleus:cytoplasmicratio appeared significantly increased in group II and reducedin group III. Low oestradiol impregnation obtained with an oralminidosed contraceptive interfered with vaginal cell maturation.High oestradiol concentrations obtained during IVF protocolsinduced marked nuclear pycnosis but did not induce supra-physiologicalcell enlargement. Maximal cell size is genetically regulatedaccording to Driesch's law of volume invariance and hormonalover-stimulation has no effect on cell size. The nucleus:cytoplasmicratio appears to be a powerful parameter reflecting the oppositeeffects of hormones on cell compartments. 相似文献
14.
Gene delivery systems are designed to control the location of administered therapeutic genes within a patient's body. Successful in vivo gene transfer may require (i) the condensation of plasmid and its protection from nuclease degradation, (ii) cellular interaction and internalization of condensed plasmid, (iii) escape of plasmid from endosomes (if endocytosis is involved), and (iv) plasmid entry into cell nuclei. Expression plasmids encoding a therapeutic protein can be, for instance, complexed with cationic liposomes or micelles in order to achieve effective in vivo gene transfer. A thorough knowledge of pharmaceutics and drug delivery, bio-engineering, as well as cell and molecular biology is required to design optimal systems for gene therapy. This mini-review provides a critical discussion on cationic lipid-based gene delivery systems and their possible uses as pharmaceuticals. 相似文献
15.
Voltage dependence of the pattern and frequency of discrete Ca2+ release events after brief repriming in frog skeletal muscle
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Michael G. Klein Alain Lacampagne Martin F. Schneider 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(20):11061-11066
Applying a brief repolarizing pre-pulse to a depolarized frog skeletal muscle fiber restores a small fraction of the transverse tubule membrane voltage sensors from the inactivated state. During a subsequent depolarizing test pulse we detected brief, highly localized elevations of myoplasmic Ca2+ concentration (Ca2+ “sparks”) initiated by restored voltage sensors in individual triads at all test pulse voltages. The latency histogram of these events gives the gating pattern of the sarcoplasmic reticulum (SR) calcium release channels controlled by the restored voltage sensors. Both event frequency and clustering of events near the start of the test pulse increase with test pulse depolarization. The macroscopic SR calcium release waveform, obtained from the spark latency histogram and the estimated open time of the channel or channels underlying a spark, exhibits an early peak and rapid marked decline during large depolarizations. For smaller depolarizations, the release waveform exhibits a smaller peak and a slower decline. However, the mean use time and mean amplitude of the individual sparks are quite similar at all test depolarizations and at all times during a given depolarization, indicating that the channel open times and conductances underlying sparks are essentially independent of voltage. Thus, the voltage dependence of SR Ca2+ release is due to changes in the frequency and pattern of occurrence of individual, voltage-independent, discrete release events. 相似文献
16.
17.
Alain Deschamps Ian Kaufman Alana Geist Steven S. B. Backman Karen Loo 《Journal canadien d'anesthésie》2007,54(3):183-189
PURPOSE: To evaluate the correlation between the progression of somatosensory blockade and changes in autonomic outflow following the onset of labour epidural analgesia. METHODS: Twelve labouring parturients consented to participate in the study. Baseline electrocardiogram, blood pressure (BP) and respiratory rate were recorded for ten minutes. The epidural consisted of 0.125% bupivacaine with 50 microg of fentanyl (total volume 20 mL). Measurements were repeated for ten minutes after initiation of the block. The level of sensory block was measured bilaterally with loss of sensation to ice at two-minute intervals. Wavelet transform was used to obtain heart rate (HR) and BP variability every two minutes following the loading dose of epidural medication. High frequency power of HR variability was used to assess changes in parasympathetic activity. The total power of BP variability was used to assess changes in sympathetic activity. A nonparametric repeated measures ANOVA was used for the variability data, and a Spearman rank correlation test was used to evaluate the relationship between the sensory block and HR and BP variability. RESULTS: The sensory block progressed to T9 at ten minutes post-epidural and was the mirror image of the decrease in total power of BP variability. High frequency power of HR variability increased to a plateau at six minutes post-epidural. A significant correlation was found between the increase in sensory block and the observed decrease in BP variability (r = -1.000, P = 0.0028). CONCLUSION: In this study of labouring parturients, BP variability correlated with the progression of both sympathetic and somatosensory block following epidural anesthesia, while HR variability was shown to be a surrogate marker of increased parasympathetic activity. 相似文献
18.
Emmanuel Lansac Isabelle Di Centa Nicolas Bonnet Pascal Leprince Akthar Rama Christophe Acar Alain Pavie Iradj Gandjbakhch 《European journal of cardio-thoracic surgery》2006,29(4):537-544
OBJECTIVE: Dilation of aortic annulus, sinuses of Valsalva, and sinotubular junction (STJ) diameters are the characteristic lesions of aortic root aneurysm. The remodeling technique reduces STJ diameter and creates three neosinuses of Valsalva. Alternatively, the reimplantation technique reduces both annulus and STJ diameters to the detriment of aortic root dynamics. Although the remodeling technique is recognized as the most physiological valve-sparing procedure, aortic annulus dilation may jeopardize its results. A standardized approach that combines an external subvalvular aortic prosthetic ring annuloplasty with the remodeling technique is suggested. METHODS: Eighty-three patients underwent an elective aortic root remodeling procedure, either isolated (group 1, n=34) or combined with an external subvalvular aortic prosthetic ring annuloplasty (group 2, n=49). Preoperative aortic regurgitation was 1.59+/-1.1 (group 1) and 1.97+/-1.3 (group 2) (NS). The aortic annulus was more dilated in group 2 than in group 1 (27+/-2.77 mm vs 26.4+/-2.3 mm, p<0.01). Residual aortic regurgitation > or =grade II was the conversion criteria for aortic valve replacement. RESULTS: Operative mortality was 3.6% (n=3). Intraoperative conversion for valve replacement was 32.7% in group 1 (n=11) versus 4.2% in group 2 (n=2) (p<0.001). In group 1, preoperative annulus diameter was larger for converted than for valve-spared patients (27.6+/-1.7 mm vs 25.2+/-1.5 mm, p<0.02). In group 2, implanted aortic ring significantly reduced annulus diameter (20.6+/-1.8 mm) without significant aortic valve gradient (8.3+/-3 mmHg). Follow-up was 17.2+/-13.4 months (group 1) and 10.41+/-7.95 months (group 2). Reoperation for recurrent aortic regurgitation was 13% in group 1 (n=3) versus 4.2% in group 2 (n=2). Echocardiographic follow-up found residual aortic regurgitation < or =grade I in 17 patients in group 1 (90%) versus 43 patients in group 2 (95.5%) and of grade II in two patients in group 1 (10%) and two patients in group 2 (4.5%). CONCLUSION: The addition of external aortic prosthetic ring annuloplasty improves the remodeling technique's operative reproducibility and short-term results. Therefore, its use as a systematical adjunct to the remodeling procedure is suggested. However, further long-term evaluation comparing this valve-sparing procedure to composite graft replacement should define the best surgical strategy for aortic root aneurysm. 相似文献
19.
Resolution of homonymous visual field loss documented with functional magnetic resonance and diffusion tensor imaging. 总被引:5,自引:0,他引:5
Masaki Yoshida Masahiro Ida Thien Huong Nguyen Marie-Therese Iba-Zizen Luc Bellinger Jean Louis Stievenart Takehiko Nagao Shinsuke Kikuchi Takaaki Hara Takuya Shiba Kenji Kitahara Emmanuel Alain Cabanis 《Journal of neuro-ophthalmology》2006,26(1):11-17
A 68-year-old man developed right homonymous hemianopic paracentral scotomas from acute infarction of the left extrastriate area. He was studied over the ensuing 12 months with visual fields, conventional MRI, functional MRI (fMRI), and diffusion tensor imaging (DTI). As the visual field defect became smaller, fMRI demonstrated progressively larger areas of cortical activation. DTI initially showed that the lesioned posterior optic radiations were completely interrupted. This interruption lessened in time and had disappeared by one year after onset. fMRI and DTI are innovative measures to follow functional and structural recovery in the central nervous system. This is the first reported application of these imaging techniques to acute cerebral visual field disorders. 相似文献
20.
Alain Deschamps Steven B Backman Vera Novak Gilles Plourde Pierre Fiset Daniel Chartrand 《The Journal of pharmacology and experimental therapeutics》2002,300(1):112-117
Edrophonium, an anticholinesterase, exerts a biphasic effect on cardiovascular autonomic drive in humans (lower doses enhance; higher doses reduce). Twenty-five anesthetized, mechanically respired (10 breaths. min(-1), constant tidal volume) patients were given either saline (n = 10) or edrophonium (0.01-1.0 mg. kg(-1), n = 15) following surgery. ECG, radial arterial pressure, and respiratory rate were sampled at 250 Hz to obtain time series for consecutive R-R intervals (RRIs), and systolic (SBP) and diastolic blood pressure (DBP). A Wigner distribution was used for time frequency mapping of spectral powers at high (HFP, 0.15-0.5 Hz) and low (LFP, 0.0-0.05 Hz) frequency. Edrophonium produced a dose-dependent decrease in heart rate [baseline 66.8 +/- 1.9 (S.E.M.) beats per minute; maximum decrease to 55.8 +/- 1.4 beats per minute with 1.0 mg. kg(-1), P < 0.01]. HFP of the RRI increased at low doses (0.2-0.4 mg. kg(-1); maximum increase to 111.0 +/- 58.2% baseline; P < 0.01) but decreased (-49.5 +/- 35.5% baseline; P < 0.01) at higher (1.0 mg. kg(-1)) doses. Edrophonium had no effect on SBP and DBP. HFP of SBP decreased with increasing doses (maximal decrease to -26.2 +/- 7.5% baseline, P < 0.01, 1.0 mg. kg(-1)). LFP of SBP was also decreased (-46.3 +/- 10.9% baseline, P < 0.01, 1.0 mg. kg(-1)). Edrophonium may enhance (lower dose) or reduce (higher dose) cardiovascular autonomic drive in humans, as evidenced by the significant changes it evokes in HFP of the RRI (parasympathetic drive), and in the HFP and LFP of SBP (sympathetic drive). These observations may account for the modest autonomic side effects of edrophonium when this drug is used clinically. 相似文献