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51.
Yasushi Shono Ekarat Jantratid Jennifer B. Dressman 《European journal of pharmaceutics and biopharmaceutics》2011,79(2):349-356
The aim of this study was to evaluate the utility of biorelevant dissolution tests coupled with in silico simulation technology to forecast in vivo bioperformance of poorly water-soluble bases, using nelfinavir mesylate as a model compound.An in silico physiologically based pharmacokinetic (PBPK) model for poorly water-soluble, weakly basic drugs was used to generate plasma profiles of nelfinavir by coupling dissolution results and estimates of precipitation with standard gastrointestinal (GI) parameters and the disposition pharmacokinetics of nelfinavir. In vitro dissolution of nelfinavir mesylate film-coated tablets was measured in biorelevant and compendial media. Drug precipitation in the small intestine was estimated from crystal growth theory. GI parameters (gastric emptying rate and fluid volume) appropriate to the dosing conditions (fasting and fed states) were used in the PBPK model. The disposition parameters of nelfinavir were estimated by fitting compartmental models to the in vivo oral PK data. The in vivo performance in each prandial state was simulated with the PBPK model, and predicted values for AUC and Cmax were compared to observed values.Dissolution results in FaSSIF-V2 and FeSSIF-V2, simulating the fasting and fed small intestinal conditions, respectively, correctly predicted that there would be a positive food effect for nelfinavir mesylate, but overestimated the food effect observed in healthy human volunteers. In order to better predict the food effect, an in silico PBPK simulation model using STELLA® software was evolved. Results with the model indicated that invoking drug precipitation in the small intestine is necessary to describe the in vivo performance of nelfinavir mesylate in the fasted state, whereas a good prediction under fed state conditions is obtained without assuming any precipitation. In vitro–in silico–in vivo relationships (IVISIV-R) may thus be a helpful tool in understanding the critical parameters that affect the oral absorption of poorly soluble weak bases. 相似文献
52.
Qingbo Liu M.D. Masahiro Shono Ph.D. Toshinori Kitamura F.R.C. Psych. 《Depression and anxiety》2009,26(8):E99-E105
Background: In order to further investigate the relationship of psychological well‐being with depression and anxiety. Method: Students from five universities were solicited to participate in this study and 545 students with a mean age of 20.1 (SD = 2.2) years were finally accessed to analysis. Result: All six dimensions—autonomy (AU), environment mastery (EM), personal growth (PG), positive relationships with others (PR), purpose in life (PL), and self‐acceptance (SA)—of the Scales of Psychological Well‐being Inventory (SPWB) were moderately negatively correlated with depression and anxiety as measured by the Hospital Anxiety and Depression Scale (HADS). Furthermore, due to a good fit with the present data, the model of SPWB on depression and anxiety was consistent with the theory of psychological well‐being and indicated that HADS depression was predicted by EM, PR, and SA, while HADS anxiety was predicted by AU, EM, PG, PR, and SA. Conclusion: SPWB is a reliable measure of well‐being for Japanese young adults, and the negative affectivity such as depression and anxiety is to some extent determined by the lack of psychological well‐being. Depression and Anxiety, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
53.
Gastric volvulus is an infrequently encountered clinical entity characterized by abnormal rotation of the stomach. Surgical treatment by anterior gastropexy is indicated for acute and chronic gastric volvulus. Recently, laparoscopic surgery has been used in abdominal surgery. We report the case of a patient with chronic gastric volvulus who was treated by laparoscopic gastropexy and evaluated by upper gastrointestinal series and endoscopic appearance of the stomach. The laparoscopic approach is safe and effective for patients and is considered applicable to surgery for other upper gastrointestinal disorders requiring organ fixation. 相似文献
54.
Orexin-A and orexin-B are hypothalamic peptides and regulate feeding behavior, energy metabolism and the sleep-wake cycle. Orexin-A binds equally to both orexin-1 and orexin-2 receptors, while orexin-B has a preferential affinity for orexin-2 receptors. Orexin-A and orexin-B are concentrated in superficial laminae of the spinal dorsal horn, and orexin-A and orexin-1 receptors are found in the dorsal root ganglion cells. Intravenous injection of orexin-A produces an anti-thermal hyperalgesic effect in the carrageenan test and this effect of orexin-A was mediated by the activation of orexin-1 receptor at the peripheral primary afferent terminal. Intrathecal and intracerebroventricular injection of orexin-A produces an analgesic effect in the formalin test and the carrageenan test and the neuropathic pain models and these effects of orexin-A are thought to be mediated by the activation of orexin-1 receptor. In the isolated spinal cord preparation from 0-to 3-day old rats, a slow depolarizing response induced by single shock stimulation of a dorsal root at C-fiber strength and wind-up phenomenon were effectively attenuated by the application of orexin-A, orexin-B and [Ala11 D-Leu15] orexin-B, a selective orexin-2 receptor agonist. This suggested that, in the neonatal rat spinal cord, orexin-2 receptor, but not orexin-1 receptor, is involved in the nociceptive transmission. 相似文献
55.
Koichi Node Ryoma Michishita Toshiyuki Tsuruta Naoko Shono Teruo Inoue 《The American journal of the medical sciences》2010,339(2):152-156
IntroductionIt has been well known that physical inactivity is associated with a significantly higher incidence of coronary artery disease. This study aimed to test our hypothesis that endurance aerobic exercise training has cardiovascular protective effects as a result of inhibiting inflammatory processes.MethodsForty-two overweight women [age, 53.4 ± 9.8 years; body mass index (BMI), 28.0 ± 2.8] received electric bicycle ergometer exercise therapy at the lactate threshold intensity for 30 to 60 minutes per day, 1 to 6 times per week for 6 weeks. The exercise training was performed within the possible load (exercise duration and frequency) for each subject.ResultsLeukocyte, monocyte, and neutrophil counts significantly decreased after the exercise therapy (P < 0.05). In simple regression analysis, percent changes in monocyte and neutrophil counts were correlated with percent changes in fasting triglyceride levels, insulin sensitivity index, BMI, and maximal oxygen uptake (VO2max). In stepwise multiple regression analysis, the percent change in monocyte counts was associated with percent changes in fasting triglyceride and VO2max (r2 = 0.368, P < 0.001), and the percent change in neutrophil counts was associated with percent changes in insulin sensitivity index and BMI (r2 = 0.292, P < 0.001).ConclusionsEndurance aerobic exercise training can influence some inflammatory processes. Furthermore, increased aerobic capacity may be antiinflammatory and have cardiovascular protective effects in overweight women. 相似文献
56.
Yamada T Nishimura G Nishida K Sawai H Omatsu T Kimura T Nishihara H Shono R Shimada S Morikawa M Mizushima M Yamada T Cho K Tanaka S Shirato H Minakami H 《The journal of obstetrics and gynaecology research》2011,37(2):151-155
We present a case of short-rib polydactyly syndrome (SRPs) type 3 in which accurate prenatal diagnosis was feasible using both ultrasonography and 3D-CT. SRP encompass a heterogeneous group of lethal skeletal dysplasias. However, the phenotypes overlap with those of nonlethal skeletal dysplasias (i.e. Ellis-van Creveld syndrome and Jeune syndrome). As accurate prenatal diagnosis of SRP is helpful for parents, we used 3D-CT in the early third trimester to examine a fetus suggested to have phenotypes of 'short-rib dysplasia group' on ultrasonography. 3D-CT showed mild modification of the vertebral bodies, small ilia with horizontal acetabula and triangular partial ossification defects, and subtle metaphyseal irregularities of the femora. These CT findings and an extensive literature search regarding the phenotypes of various diseases categorized as short-rib dysplasia group led to a correct prenatal diagnosis of SRP type 3. This case exemplified the usefulness of 3D-CT for the precise prenatal diagnosis of skeletal dysplasias. 相似文献
57.
Kusumoto G Sugi Y Higa K Shono S Nitahara K 《Masui. The Japanese journal of anesthesiology》2008,57(8):1037-1040
We compared training of internal jugular vein cannulation with ultrasound-guided method and that with landmark method in a group of 10 residents and that of 10 staffs. Cannulation was increasingly successful with both methods as the training proceeded, and with increasingly less time and fewer number of punctures. There was no statistically significant difference in time or in number of punctures with ultrasound-guided method between the groups. Ultrasound-guided method needed fewer number of punctures than those with landmark method in both groups. 相似文献
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