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Bill J Gurley Ashley Swain Gary W Barone D Keith Williams Philip Breen C Ryan Yates Leslie B Stuart Martha A Hubbard Yudong Tong Sreekhar Cheboyina 《Drug metabolism and disposition》2007,35(2):240-245
Phytochemical-mediated modulation of P-glycoprotein (P-gp) and other drug transporters may give rise to many herb-drug interactions. Serial plasma concentration-time profiles of the P-gp substrate, digoxin, were used to determine whether supplementation with goldenseal or kava kava modified P-gp activity in vivo. Twenty healthy volunteers were randomly assigned to receive a standardized goldenseal (3210 mg daily) or kava kava (1227 mg daily) supplement for 14 days, followed by a 30-day washout period. Subjects were also randomized to receive rifampin (600 mg daily, 7 days) and clarithromycin (1000 mg daily, 7 days) as positive controls for P-gp induction and inhibition, respectively. Digoxin (Lanoxin, 0.5 mg) was administered p.o. before and at the end of each supplementation and control period. Serial digoxin plasma concentrations were obtained over 24 h and analyzed by chemiluminescent immunoassay. Comparisons of area under the curve (AUC)((0-3)), AUC((0-24)), C(max,) CL/F, and elimination half-life were used to assess the effects of goldenseal, kava kava, rifampin, and clarithromycin on digoxin pharmacokinetics. Rifampin produced significant reductions (p < 0.01) in AUC((0-3)), AUC((0-24)), CL/F, t(1/2), and C(max), whereas clarithromycin increased these parameters significantly (p < 0.01). With the exception of goldenseal's effect on C(max) (14% increase), no statistically significant effects on digoxin pharmacokinetics were observed following supplementation with either goldenseal or kava kava. When compared with rifampin and clarithromycin, supplementation with these specific formulations of goldenseal or kava kava did not appear to affect digoxin pharmacokinetics, suggesting that these supplements are not potent modulators of P-gp in vivo. 相似文献
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A preliminary report of the short-term effect of carbonated beverage consumption on calcium metabolism in normal women 总被引:2,自引:0,他引:2
S Smith J Swain E M Brown G Wyshak T Albright V A Ravnikar I Schiff 《Archives of internal medicine》1989,149(11):2517-2519
A variety of nutritional factors influence the bioavailability of calcium and increase a woman's risk of osteoporosis. Eight healthy women completed an 8-week metabolic study designed to investigate the effect of nonalcoholic carbonated beverage consumption on calcium metabolism. Compared with women receiving a control diet, women consuming a diet high in nonalcoholic carbonated beverages demonstrated similar mean serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxyvitamin D3, and osteocalcin. Twenty-four-hour urine volume, creatinine clearance, calcium-creatinine ratio, and phosphorus-creatinine ratio were similar during consumption of the diet high in nonalcoholic carbonated beverages and the control diet. Twenty-four-hour cyclic adenosine monophosphate-creatinine ratio was significantly lower in women consuming the diet high in nonalcoholic carbonated beverage compared with women receiving the control diet (342 +/- 27.4 nmol/mmol vs 409 +/- 22.1 nmol/mmol). Consumption of a diet high in nonalcoholic carbonated beverages on a short-term basis does not appear to affect adversely the serum or urinary markers of calcium metabolism. 相似文献
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Phospho-akt expression is associated with a favorable outcome in non-small cell lung cancer. 总被引:3,自引:0,他引:3
Amit Shah William A Swain Donna Richardson John Edwards Duncan J Stewart Catherine M Richardson Daniel E B Swinson Dipika Patel J Louise Jones Kenneth J O'Byrne 《Clinical cancer research》2005,11(8):2930-2936
Akt, a Serine/Threonine protein kinase, mediates growth factor-associated cell survival. Constitutive activation of Akt (phosphorylated Akt, P-Akt) has been observed in several human cancers, including lung cancer and may be associated with poor prognosis and chemotherapy and radiotherapy resistance. The clinical relevance of P-Akt in non-small cell lung cancer (NSCLC) is not well described. In the present study, we examined 82 surgically resected snap-frozen and paraffin-embedded stage I to IIIA NSCLC samples for P-Akt and Akt by Western blotting and for P-Akt by immunohistochemistry. P-Akt protein levels above the median, measured using reproducible semiquantitative band densitometry, correlated with a favorable outcome (P = 0.007). Multivariate analysis identified P-Akt as a significant independent favorable prognostic factor (P = 0.004). Although associated with a favorable prognosis, high P-Akt levels correlated with high tumor grade (P = 0.02). Adenocarcinomas were associated with low P-Akt levels (P = 0.039). Akt was not associated with either outcome or clinicopathologic variables.Cytoplasmic (CP-Akt) and nuclear (NP-Akt) P-Akt tumor cell staining was detected in 96% and 42% of cases, respectively. Both CP-Akt and NP-Akt correlated with well-differentiated tumors (P = 0.008 and 0.017, respectively). NP-Akt also correlated with nodal metastases (P = 0.022) and squamous histology (P = 0.037).These results suggest P-Akt expression is a favorable prognostic factor in NSCLC. Immunolocalization of P-Akt, however, may be relevant as NP-Akt was associated with nodal metastases, a known poor prognostic feature in this disease. P-Akt may be a potential novel therapeutic target for the management of NSCLC. 相似文献
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H. Kienapfel R. Swain A. Hettel A. Wilke M. Koller P. Griss 《Archives of orthopaedic and trauma surgery》1997,116(4):239-243
Thirty cylindrical, commercially pure, titanium fiber, porous-coated Ti6Al4V implants were inserted pressfit into the proximal humeral portion of 30 sheep humeri to determine the systemic effect of recombinant factor XIII and placenta-derived factor XIII concentrate on bone ingrowth and strength of fixation. For both the recombinant factor XIII and the factor XIII concentrate group, the volume of bone ingrowth and the strength of fixation were higher than for the control specimens. However, the difference was only significant for the factor XIII concentrate group. 相似文献
6.
Comparative assessment of chordal preservation versus chordal resection during mitral valve replacement 总被引:7,自引:0,他引:7
H A Hennein J A Swain C L McIntosh R O Bonow C D Stone R E Clark 《The Journal of thoracic and cardiovascular surgery》1990,99(5):828-36; discussion 836-7
Left ventricular function often deteriorates after mitral valve replacement for mitral regurgitation. It has been postulated that disruption of the mitral valve apparatus at operation is a major mechanism of postoperative dysfunction. The hypothesis tested in this investigation was that chordal preservation results in more favorable left ventricular function. Sixty-nine patients with isolated mitral regurgitation who underwent mitral valve replacement were studied before and 6 months after operation by treadmill exercise testing, catheterization, echocardiography, and radionuclide angiography. Nine patients underwent mitral valve replacement with preservation of the entire mitral apparatus and five with preservation of the posterior leaflet and attached chordae. The remaining 55 had mitral valve replacement with complete excision of the native valve. Preoperatively, there were no differences among groups in age, gender, exercise capacity, cardiac index, rest or exercise ejection fraction, fractional shortening, or pulmonary artery pressures. There were four perioperative deaths (7%) and eight late deaths among the 55 patients with chordal resection but no early or late deaths of patients whose chordae were preserved (p = 0.05). In patients in whom the chordae were excised, exercise capacity, left ventricular systolic dimensions, and cardiac index did not improve after mitral valve replacement, and left ventricular function deteriorated, as evidenced by a reduction of both the resting and exercise ejection fractions (from 46% +/- 13% to 31% +/- 13%, p = 0.0001, and from 49% +/- 12% to 37% +/- 14%, p = 0.0007, respectively) and fractional shortening (from 34% +/- 10% to 26% +/- 14%, p = 0.0001). In contrast, exercise capacity improved after mitral valve replacement in patients in whom the entire apparatus was spared (by 4 +/- 3 minutes, p = 0.05), left ventricular systolic dimensions decreased (from 44 +/- 8 to 36 +/- 9 mm, p = 0.03), and left ventricular function was maintained or improved, as evidenced by preservation of the resting ejection fraction (preoperative, 50% +/- 14%; postoperative, 54% +/- 11%; p = no significant difference), exercise ejection fraction (46% +/- 16% versus 52% +/- 9%, p = no significant difference), fractional shortening (from 31% +/- 9% to 28% +/- 9%, p = no significant difference), and an increase in the cardiac index (from 2.0 +/- 0.3 to 2.7 +/- 0.5 L/min/m2, p = 0.05). No statistically significant differences between posterior chordal resection only and preservation of the entire apparatus were found.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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In vivo transfer and expression of a human epidermal growth factor gene accelerates wound repair. 总被引:18,自引:0,他引:18 下载免费PDF全文
C Andree W F Swain C P Page M D Macklin J Slama D Hatzis E Eriksson 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(25):12188-12192
This report details the transfer of a human epidermal growth factor (hEGF) expression plasmid to porcine partial-thickness wound keratinocytes by particle-mediated DNA transfer (Accell). After gene transfer an external sealed fluid-filled wound chamber was used to protect the wound, provide containment of the exogenous DNA and expressed peptide, and permit sampling of the wound fluid. Analysis of wound fluid for hEGF and total protein, an indicator of reformation of the epithelial barrier, showed that wounds bombarded with the hEGF plasmid exhibited a 190-fold increase in EGF concentration and healed 20% (2.1 days) earlier than the controls. EGF concentrations in wound fluid persisted over the entire 10-day monitored period, decreasing from 200 pg/ml to 25 pg/ml over the first 5 days. Polymerase chain reaction results showed that plasmid DNA was present in the wound for at least 30 days. These findings demonstrate the possible utility of in vivo gene transfer to enhance epidermal repair. 相似文献