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Transport of Pregabalin in Rat Intestine and Caco-2 Monolayers   总被引:4,自引:0,他引:4  
Purpose. The purpose of this study was to determine if the intestinal transport of pregabalin (isobutyl --aminobutyric acid, isobutyl GAB A), a new anticonvulsant drug, was mediated by amino acid carriers with affinity for large neutral amino acids (LNAA). Methods. Pregabalin transport was studied in rat intestine and Caco-2 monolayers. An in vitro Ussing/diffusion chamber model and an in situ single-pass perfusion model were used to study rat intestinal transport. An in vitro diffusion chamber model was used to evaluate Caco-2 transport. Results. In rat ileum, pregabalin transport was saturable and inhibited by substrates of intestinal LNAA carriers including neurontin (gabapentin), phenylalanine, and proline. Weak substrates of intestinal LNAA carriers (-alanine, --aminobutyric acid, and methyl aminoisobutyric acid) did not significantly change pregabalin transport. In Caco-2 mono-layers that showed a high capacity for phenylalanine transport, pregabalin transport was concentration- and direction-independent and equivalent in magnitude to the paracellular marker, mannitol. The in vitro and in situ rat ileal permeabilities of the LNAA carrier-mediated compounds neurontin, pregabalin, and phenylalanine correlated well with the corresponding in vivo human oral absorption. Conclusions. The transport of pregabalin was mediated by LNAA carriers in rat ileum but not in Caco-2 monolayers. Caco-2 was not an appropriate model for evaluating the in vivo human oral absorption of pregabalin and neurontin.  相似文献   
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There is a need for consistent, repetitive, and reliable terminology to describe the basic manipulations of the ultrasound transducer. Previously, 5 basic transducer motions have been defined and used in education. However, even with this effort, there is still a lack of consistency and clarity in describing transducer manipulation and motion. In this technical innovation, we describe an expanded definition of transducer motions, which include movements to change the transducer's angle of insonation to the target as well as the location on the body to optimize the ultrasound image. This new terminology may allow for consistent teaching and improved communication in the process of image acquisition.  相似文献   
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This was a 6-week, randomized, double-blind, multicenter study evaluating the efficacy of pregabalin in the treatment of painful diabetic neuropathy. Two hundred forty-six men and women with painful diabetic neuropathy received pregabalin (150 or 600 mg/day by mouth) or placebo. The primary efficacy variable was mean pain score at the end of treatment. Efficacy results indicate that pregabalin 600 mg/day significantly decreased mean pain score to 4.3 (vs 5.6 for placebo, P = .0002) and increased the proportion of patients who had a > or =50% decrease from baseline pain (39% vs 15% for placebo, P = .002). Pregabalin also significantly reduced sleep interference, past week and present pain intensity, sensory and affective pain scores, and bodily pain and decreased by > or =50% the number of patients describing their pain as gnawing, sickening, fearful, and punishing-cruel. More patients receiving pregabalin 600 mg/day than placebo showed improvement, as rated on the Clinical and Patient Global Impression of Change scales, 73% vs 45% and 85% vs 47%, respectively. Pregabalin 150 mg/day was essentially no different from placebo. Dizziness was the most common side effect. These study results show pregabalin 600 mg/day to be safe and effective in reducing the pain and other associated symptoms of painful diabetic neuropathy. PERSPECTIVE: Painful diabetic peripheral neuropathy is a challenging neuropathic pain syndrome. This randomized controlled trial demonstrates that pregabalin, a new drug that interacts with the alpha2-delta protein subunit of the voltage-gated calcium channel, is an efficacious and safe treatment for the pain of this condition.  相似文献   
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OBJECTIVE: The steady state visual evoked potential (SSVEP) can be used to test the frequency response function of neural circuits. Previous studies have shown reduced SSVEPs to alpha and lower frequencies of stimulation in schizophrenia. We investigated SSVEPs in schizophrenia at frequencies spanning the theta (4Hz) to gamma (40Hz) range. METHODS: The SSVEPs to seven different frequencies of stimulation (4, 8, 17, 20, 23, 30 and 40Hz) were obtained from 18 schizophrenia subjects and 33 healthy control subjects. Power at stimulating frequency (signal power) and power at frequencies above and below the stimulating frequency (noise power) were used to quantify the SSVEP responses. RESULTS: Both groups showed an inverse relationship between power and frequency of stimulation. Schizophrenia subjects showed reduced signal power compared to healthy control subjects at higher frequencies (above 17Hz), but not at 4 and 8Hz at occipital region. Noise power was higher in schizophrenia subjects at frequencies between 4 and 20Hz over occipital region and at 4, 17 and 20Hz over frontal region. CONCLUSIONS: SSVEP signal power at beta and gamma frequencies of stimulation were reduced in schizophrenia. Schizophrenia subjects showed higher levels of EEG noise during photic stimulation at beta and lower frequencies. SIGNIFICANCE: Inability to generate or maintain oscillations in neural networks may contribute to deficits in visual processing in schizophrenia.  相似文献   
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Case reports and sensory inventories suggest that autism involves sensory processing anomalies. Behavioral tests indicate impaired motion and normal form perception in autism. The present study used first-person accounts to investigate perceptual anomalies and related subjective to psychophysical measures. Nine high-functioning children with autism and nine typically-developing children were given a questionnaire to assess the frequency of sensory anomalies, as well as psychophysical tests of visual perception. Results indicated that children with autism experience increased perceptual anomalies, deficits in trajectory discrimination consistent with dysfunction in the cortical dorsal pathway or in cerebellar midsagittal vermis, and high spatial frequency contrast impairments consistent with dysfunctional parvocellular processing. Subjective visual hypersensitivity was significantly related to greater deficits across vision tests.  相似文献   
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A lipophilic derivative of the known GABA uptake inhibitor guvacine has been prepared. The synthesis of this compound, [1-]2-bis 4-(trifluoromethyl)]phenyl[-methoxy]ethyl[- 1,2,5,6-tet-rahydro-3-pyridine carboxylic acid, monohydrochloride, Cl-966, is described. Studies were carried out to determine the metabolic profile of Cl-966, in rats. Two metabolites, one less polar and the other more polar than Cl-966, were identified and their structures assigned by spectroscopic methods and confirmed by comparison to synthetic material.  相似文献   
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Formation of [20R]-dihydrodigoxin from digoxin in humans   总被引:2,自引:0,他引:2  
The objective of this research was to determine the stereochemical identity of dihydrodigoxin (DHD3), a metabolite of digoxin excreted in urine after digoxin administration in man. Separation of the individual epimers in reference DHD3 was effected by a chemical derivatization-HPLC procedure. Comparison of individual derivatized epimers of DHD3 with the known 20R and 20S epimers of derivatized dihydrodigoxigenin using chromatographic data and NMR spectroscopy permitted identification of the 20R and 20S epimers in reference DHD3. Material corresponding chromatographically to R-DHD3 was isolated from urine of a volunteer taking oral digoxin daily. The NMR spectrum of the chromatographically pure, derivatized urinary isolate was identical to the NMR spectrum of derivatized R-DHD3. Urine samples from 20 patients on chronic digoxin therapy and from two volunteers were surveyed for chromatographic evidence of R- or S-DHD3 using HPLC of a fluorescent derivative as well as HPLC of a UV-absorbing derivative. The more sensitive fluorescence procedure yielded evidence for R-DHD3 in eight patients and both volunteers. There was a sufficient concentration in four patients and both volunteers for independent evidence of R-DHD3 using the UV-absorbing derivative. Chromatographic evidence (fluorescent derivative) for S-DHD3 was found in urine from three patients. However, this evidence for S-DHD3 was demonstrated to be an artifact by the absence of the peak expected for S-DHD3 in the chromatogram of the UV-absorbing derivative as well as by the inability of fecal incubates to convert digoxin to S-DHD3. The results of the investigation indicate that the DHD3 metabolite formed in humans is the 20R epimer.  相似文献   
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