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11.
Chien Yie W. Chien Te-yen Bagdon Robert E. Huang Yih C. Bierman Robert H. 《Pharmaceutical research》1989,6(12):1000-1010
Several transdermal contraceptive device (TCD) formulations were developed to provide a dual-controlled transdermal delivery of levonorgestrel (LN), a potent progestin, and 17-estradiol (E2), a natural estrogen. Using a sensitive HPLC method, the in vitro release and skin permeation profiles of LN and E2 from various TCD formulations were simultaneously characterized in the hydrodynamically well-calibrated Valia–Chien skin permeation cells and both were found to follow zero-order kinetics. The rates of drug release and skin permeation were observed to vary significantly depending upon some formulation parameters. Six-month stability studies were performed on seven formulations at room and elevated temperatures (37 and 45°C), and two (Formulations 4 and 5) were found to be acceptable, based on drug recovery, release rate, and skin permeation rate data. Judging from the 6-month accelerated stability studies, it is projected these two formulations will have shelf-life of at least 2 years. As a result of development of an efficient manufacturing process, Formulation 4 was selected for further evaluation. One-week primary skin irritation evaluation in 6 rabbits indicated that Formulation 4 is nonirritating, and it was thus selected for Phase I clinical bioavailability/dose proportionality studies in 12 healthy female volunteers of child-bearing age. Results of pharmacokinetic and pharmacodynamic analyses demonstrated that it is capable of achieving and maintaining a steady-state serum level of LN throughout the 3-week treatment period by weekly applications of one or two TCD patches (10 or 20 cm2). A dose proportionality was obtained in the serum drug levels, daily dose delivered, and contraception efficacy. An excellent correlation was obtained for the rates of transdermal delivery determined by the in vitro studies using human cadaver skin, the in vivo studies in rabbits, and the clinical studies in living subjects. 相似文献
12.
Chu PH Yeh HI Jung SM Chien LY Cheng NF Wu HH Chu JJ Hsueh C Lee YS 《Virchows Archiv : an international journal of pathology》2004,444(4):383-386
Cardiac hamartomas are very rare and are demarcated masses of enlarged, hypertrophied, mature myocytes and collagen tissue. Cardiac hamartomas are generally circumscribed in the right ventricle or atrium, but not reported in the crista terminalis (CRT). The CRT is crucial in electrophysiology, is related to arrhythmogenesis, and is targeted by radiofrequency catheter procedures. Previous works only described the benign natures of prominent CRT using non-invasive methods. This study describes an unusual cardiac hamartoma originating from the CRT and extending toward the tricuspid valve. Microscopically, this hamartoma comprised dense collagen and adipose tissue, mixed with hypertrophy, but with disarrayed cardiomyocytes. An irregular gap junction, connexin43, was demonstrated in this cardiac hamartoma. 相似文献
13.
Schweigart G Chien RD Mergner T 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2002,147(1):89-97
Vestibular functions are known to show some deterioration with age. Vestibular deterioration is often thought to be compensated
for by an increase in neck proprioceptive gain. We studied this presumed compensatory mechanism by measuring psychophysical
responses to vestibular (horizontal canal), neck and combined stimuli in 50 healthy human subjects as a function of age (range
15–76 years). After passive horizontal rotations of head and/or trunk (torso) in complete darkness (dominant frequencies 0.05,
0.1, and 0.4 Hz), subjects readjusted a visual target to its remembered prerotational location in space. (1) Vestibular-only stimulus (whole-body rotation); subjects' responses were shifted towards postrotatory body position, this only slightly at 0.4 Hz and
pronounced at 0.1 and 0.05 Hz. These errors reflect the known physiological drop of vestibular gain at low rotational frequency.
They exhibited a slight but significant increase with age. (2) Neck-only stimulus (trunk rotated, head stationary); the responses showed errors similar to those upon vestibular stimulation (with offset towards
postrotatory trunk position) and this again slightly more with increasing age. (3) Vestibular-neck stimulus combination during head rotation on stationary trunk; the errors were close to zero, independent of stimulus frequency and the subjects'
age. (4) Opposite stimulus combination (trunk rotated in the same direction as the head, but with double amplitude); the errors were clearly enhanced, essentially
reflecting the sum of those with vestibular-only and neck-only stimulation. Taken together, we find a parallel increase in
neck- and vestibular-related errors with age, in seeming contrast to previous studies. We explain our and the previous findings
by a vestibular-neck interaction model in which two different neck signals are involved. One neck signal is used, in combination
with the vestibular signal, for estimating trunk-in-space rotation. It is internally shaped to always match the vestibular
signal, so that these two signals cancel each other out when summed during head rotation on stationary trunk. Because of this
matching, perceived trunk stationariness during head rotation on the stationary trunk is independent of vestibular deterioration
(related to stimulus frequency, age, ototoxic medication, etc.). The other neck proprioceptive signal, coding head-on-trunk
rotation, is superimposed on the estimate of trunk-in-space rotation, thereby yielding a notion of head-in-space. This neck
signal remains essentially unchanged with vestibular deterioration. Generally, we hold that the transformation of the vestibular
signal from the head down to the trunk proceeds further to include the hip and the legs as well as the haptically perceived
body support surface; by this, subjects yield a notion of support kinematics in space. As a consequence, spatial orientation
is impaired by chronic vestibular deterioration only to the extent that the body support is moving in space, while it is unimpaired
(determined by proprioception alone) during body motion with respect to a stationary support.
Electronic Publication 相似文献
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Understanding the difference between the development of a productive T‐cell response and tolerance is central to discerning how the immune system functions. Intravenous injection of soluble protein is thought to mimic the presentation of self‐serum and orally introduced antigens. It is generally toleragenic. The current view is that this outcome reflects the failure of ‘immunogenic’ dendritic cells to relocate to the T‐cell zone of the secondary lymphoid tissues. Here, using a peptide/I‐Ek tetramer and antibodies to stain splenic sections, we showed that antigen‐specific T cells were activated in the spleen within hours of injection or feeding of protein. The activated T cells were found to be located at the T–B junction, the bridging zone and the B‐cell area, interacting directly with B cells. In addition, B cells gain the ability to present antigen. Our results suggest a way for T cells to be stimulated by blood‐borne antigen presented by naïve B cells, a potential mechanism of tolerance induction. 相似文献
17.
Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. 总被引:1,自引:1,他引:1 下载免费PDF全文
K. P. Burton L. M. Buja A. Sen J. T. Willerson K. R. Chien 《The American journal of pathology》1986,124(2):238-245
Alterations in triacylglycerol and phospholipid metabolism are known to occur during the evolution of myocardial ischemic injury. The purpose of this study was to explore potential relationships between the accumulation of arachidonic acid and other fatty acids, the accumulation of triacylglycerol, and the progression of myocardial injury. Measurements of the fatty acid levels in triacylglycerol, unesterified fatty acids, and calcium content were correlated with myocardial function during ischemia and ischemia with reflow in an isolated perfused rat heart preparation. After 10 minutes of ischemia in this model, myocardial dysfunction was reversible, with recovery of left ventricular +dP/dt to 82.0% +/- 4.8% of control values upon reperfusion. Hearts did not recover with reperfusion after 30 minutes of ischemia and displayed a significant increase in tissue calcium content. A significant, nearly threefold increase in the arachidonic acid content of triacylglycerol was found after 10 minutes of ischemia and continued to increase with longer periods of ischemia and reflow. Other fatty acids also showed increased levels in triacylglycerol. The time course of accumulation of unesterified arachidonic acid paralleled the loss of myocardial function. Levels of free arachidonic acid were (in nanomoles per gram wet weight) 11.1 +/- 2.1 (SEM) for control hearts, 17.3 +/- 1.9 after 10 minutes of ischemia, and 38.4 +/- 2.5 after 30 minutes of ischemia. Increases in other free fatty acids contributed to a significant increase in total free fatty acid accumulation after 30 minutes of ischemia. Thus, the content of arachidonic and other fatty acids in triacylglycerol was found to increase early during ischemia, and a major increase in free arachidonic and other unesterified fatty acids occurred after a longer period of ischemia. These findings are consistent with an initial reincorporation of free fatty acids into triacylglycerol after release from membrane phospholipids, suggesting that membrane fatty acids may be a major source of triacylglycerol that accumulates in ischemic myocardium. In addition, these results suggest that a major increase in free fatty acids during ischemia and ischemia with reflow correlates temporally with the development of severe contractile dysfunction and accumulation of calcium in the heart. 相似文献
18.
Shyh Ren Chiang Hung Jen Tang Ping Chin Chang Kuo Chen Cheng Wen Chien Ko Chung Hua Chen Yin Ching Chuang 《Journal of microbiology, immunology, and infection》2007,40(2):123-133
BACKGROUND AND PURPOSE: Vibrio vulnificus causes primary bacteremia and necrotizing wound infection, leading to high morbidity and mortality in humans. This study aimed to evaluate the antimicrobial effect of cefotaxime and minocycline on proinflammatory cytokine levels in a murine model of V. vulnificus infection. METHODS: We investigated the dynamics of proinflammatory cytokines and their modulation by antimicrobial agents using a murine model of V. vulnificus infection. The change in cytokine levels was followed over a time course to identify the antimicrobial activity of the drugs against V. vulnificus. BALB/c female mice were challenged with an intraperitoneal infection using a clinical invasive isolate of Vv05191, and their cytokine levels were assayed over various time points. RESULTS: Serum levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, and IL-6 post-infection were found to be inoculum dose-dependent and positively correlated to the subsequent fatality rate in the infected mice. With an inoculum of 6.6 x 10(6) colony-forming units and intraperitoneal administration of cefotaxime, minocycline, or both, the serum and peritoneal fluid cytokine levels increased and then declined gradually. Comparison of the 3 antimicrobial regimens revealed that the magnitude of reduction in cytokine levels was greatest in mice treated with cefotaxime-minocycline combination. Moreover, the peritoneal fluid cytokine level in the combination group was significantly lower than that in the groups treated with minocycline or cefotaxime alone. CONCLUSIONS: The current results support the superiority of the combination therapy in treating invasive V. vulnificus infections. 相似文献
19.
Mao-Tsair Lin Yin-Hsiu Chien Shyh-Dar Shyur Li-Hsin Huang Yi-Chi Chiang Da-Chin Wen Pei-Hsuan Liang Hwai-Chih Yang 《Annals of allergy, asthma & immunology》2006,96(5):744-748
BACKGROUND: X-linked agammaglobulinemia (XLA), characterized by a profound deficiency of all immunoglobulins and the absence of mature B cells, is caused by mutations in the gene encoding Bruton tyrosine kinase (BTK). Most patients have recurrent sinopulmonary infection. Infections usually occur in multiple locations across time, but single infection may be limited to one anatomic location. OBJECTIVES: To report a case of atypical XLA with recurrent pyoderma and to observe the immunologic changes in the patient in 10 years. METHODS: Immunologic investigations, skin wound culture, and molecular study with DNA sequencing were performed. RESULTS: The patient was originally diagnosed as having common variable immunodeficiency disease because of the presence of circulating B cells (CD19+ B cells: 7%) at 11 years old. On further evaluation at the age of 20 years, flow cytometric analysis of lymphocytes showed only 0.4% B cells. The molecular study with DNA sequencing of the patient showed a point mutation in complementary DNA 1630 A>G(p.R544G) in the BTK gene, indicating that the patient has XLA. The mutation analysis of the BTK gene revealed a normal DNA sequence in the other family members. CONCLUSIONS: This case is an important example of a possible presentation of XLA with a predominant skin manifestation, and it demonstrates that maintaining a high level of clinical suspicion is essential for the diagnosis of XLA in a child with recurrent pyoderma. 相似文献
20.
Jo BJ Chung TS Lee MS Joo JY Ebert W Weinmann HJ Chien D Laub G 《Yonsei medical journal》1999,40(5):413-419
The purpose of this study was to compare the image quality of 3D-TOF MR angiography (MRA) using Gadomer-17 with that using Gd-DTPA in a flow phantom model, and to present preliminary data about the proper dose concentration of Gadomer-17. In the visual analysis of vessel conspicuity, we compared the quality of pre- and post-contrast MIP images. For quantitative analysis, the signal intensities were measured in the axial base 3D-TOF images, and then the relative contrast enhancement was calculated. The results of our studies were that: 1. Maximal signal intensities were obtained at 1 mmol/L of Gadomer-17 and 4 mmol/L of Gd-DTPA. 2. Flow-related signal loss was decreased by Gd-DTPA proportional to the concentration, but Gadomer-17 did not show such a dose accumulative effect. In conclusion, after comparing the results of Gd-DTPA, it was clear that improved MRA images and higher signal intensities of vessels were obtained when lower concentrations of Gadomer-17 were used. 相似文献