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31.
Iontophoresis is useful for the transdermal delivery of charged drugs. However, nonionized drugs either have a low flux (due to electro-osmosis) or cannot be delivered using this technique. Because ionized or nonionized drugs can be encapsulated in charged liposomes, it was hypothesized that charged liposomes can deliver neutral or nonionized drug efficiently by iontophoresis. Colchicine, a neutral drug, was encapsulated in large unilamellar vesicles (LUVs), prepared with 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) along with cholesterol (1:0.5 mole ratio). Multilamellar vesicles (MLVs) were prepared by the thin-film hydration method and LUVs were obtained by extruding MLVs through polycarbonate filters of 200 nm pore size. Positive charge was induced in the liposomes by adding stearylamine and negative charge by adding dicetyl phosphate. Nonencapsulated drug was separated from LUVs by the Ficoll density gradient method. Positively charged LUVs were delivered under the anode, negatively charged LUVs under the cathode, and neutral LUVs without current using Franz cells and human cadaver skin. Plain colchicine as well as colchicine encapsulated in positively charged LUVs was delivered better under the anode compared with the cathode and passive conditions. Delivery of colchicine encapsulated in positively charged DSPC liposomes was four to five times greater than that of plain colchicine and two to three times greater than that of colchicine encapsulated in DMPC or DPPC liposomes. Because LUVs prepared with DMPC and DPPC were fluid at 37°C, the encapsulated drug leaked during iontophoresis and therefore the delivery was less. Delivery of colchicine was lower under the cathode due to the change in pH during iontophoresis, which, as observed in high-performance liquid chromatographic analysis, caused degradation of the drug. Thus, it can be concluded that iontophoresis of colchicine encapsulated in positively charged DSPC liposomes can improve its delivery across human cadaver skin 相似文献
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Sonpavde G 《The New England journal of medicine》2004,351(16):1690-1; author reply 1690-1
34.
Erythromycin taurate, a new derivative of erythromycin, was prepared by reacting erythromycin base with tauric acid and its physico-chemical and biological properties were evaluated. The derivative has reasonably good solubility in organic solvents. The partition coefficient values in chloroform/water 1.17 and octanol/water 1.16 systems indicate its good distribution in various tissues in vivo. The in vitro antimicrobial potency of the derivative (833.33 microg mg(-1)) is higher than that of the existing derivatives such as erythromycin estolate, erythromycin stearate, erythromycin ethyl succinate, erythromycin gluceptate, erythromycin lactobionate. The antimicrobial spectrum is comparable to that of the parent compound. Our results indicate that erythromycin taurate has a high potential for possible clinical application and is more efficient against Escherichia coli and Klebsiella pneumoniae than the parent base. 相似文献
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36.
Barai S Kumar R Mehta SN Dinda AK Yadav R Bandopadhayaya GP Tarun S Malhotra A 《International urology and nephrology》2003,35(4):451-456
OBJECTIVES: No objective parameters for renal allograft evaluation have yet been described for Tc99m-Ethylenedicystine. This study evaluates the diagnostic significance of different quantitative and semi-quantitative parameters of renal allograft scintigraphy using Tc99m-Ethylenedicystine. METHODS: A total of 72 renal dynamic scintigraphic studies were performed within 2-weeks of renal transplantation in 42 patients. The graft perfusion, kidney/aorta ratio, washout index and retention index were derived from all studies. All these parameters were evaluated for their ability to distinguish between a normal graft, a graft with acute rejection (AR), and a graft with acute tubular necrosis (ATN). Histopathological verification of diagnosis was obtained in all cases. RESULTS: Studies were subdivided into 3 groups according to histopathological findings: acute rejection (n = 42), normal (n = 18) and acute tubular necrosis (n = 12). Normal allografts were visualized with in 2.66 +/- 0.59 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 15.22 +/- 6.86, 1.67 +/- 0.45, and 5.48 +/- 0.98 respectively. Allografts with ATN were visualized with in 3.36 +/- 0.80 seconds of visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 12.73 +/- 6.74, 0.60 +/- 0.14, and 9.18 +/- 1.48 respectively. In AR, allografts were visualized 15.18 +/- 9.48 seconds after visualization of abdominal aorta. The K/A ratio, wash out index and retention index was 7.07 +/- 2.15, 0.63 +/- 0.11, and 2.26 +/- 1.28 respectively. CONCLUSIONS: Retention index can separate all the three condition of normal, acute rejection and acute tubular necrosis from each other. Retention index of < 4 suggests acute rejection, a value between 4 and 7 suggests normal allograft and a value of > or = 7 is suggestive of acute tubular necrosis. However, perfusion, K/A ratio and washout index can not segregate all the three groups. 相似文献
37.
Greenberg RK Clair D Srivastava S Bhandari G Turc A Hampton J Popa M Green R Ouriel K 《Journal of vascular surgery》2003,38(5):990-996
OBJECTIVES: Treatment of abdominal aortic aneurysm is controversial in patients at high physiologic risk for open repair and high anatomic risk for endovascular repair. We compared outcome in patients at high risk because of anatomy (short or angulated neck), severe occlusive disease, or bilateral iliac aneurysms (group A) with outcome in patients at low risk (group B). MATERIAL AND METHODS: Patients at high anatomic risk who underwent treatment between October 1998 and March 2002 with the Zenith endovascular graft (group A) were compared with patients at low anatomic risk enrolled in a prospective multicenter trial (group B). Variables compared included overall mortality, need for secondary interventions, development of endoleak, and change in aneurysm sac diameter. The chi(2) test, Student t test, and proportions analysis were used to assess the data. RESULTS: Data for 493 patients (group A, 141; group B, 352) were evaluated. Mean follow-up was 9 months (range, 1-24 months). Perioperative mortality was similar for groups A and B (0.7% vs 1%). Frequency of endoleak was higher in patients with high-risk anatomy (25% vs 11%), but not significantly so (P >.06). The rate of aneurysm shrinkage, even in the absence of endoleak, was slower in group A (P <.05). CONCLUSIONS: In physiologically challenged patients at higher anatomic risk for endovascular aneurysm repair, initial mortality rate is similar to that in patients at lower risk. Short-term technical results are acceptable. Decreased long-term survival (largely unrelated to the procedure), slightly higher frequency of endoleak, and a lower rate of sac shrinkage may temper enthusiasm for endovascular repair in this subgroup. Risks of repairing aneurysms in this patient population must be viewed in the context of expected results of intervention or medical observation. 相似文献
38.
Conjeevaram R Chaturvedula A Betageri GV Sunkara G Banga AK 《Pharmaceutical research》2003,20(9):1496-1501
Purpose. To demonstrate the in vivo transdermal delivery and establish the comparative pharmacokinetics of five -blockers in hairless rat.
Methods. Intravenous dosing was initially done via jugular cannula. For iontophoretic delivery, current (0.1 mA/cm2) was applied for 2 h through a drug reservoir patch containing the -blocker (10 mg/ml). Blood samples were collected and analyzed by stereoselective HPLC assays. Any irritation resulting from patch application was quantified by a chromameter. Multilamellar liposomal formulation was prepared by the thin-film hydration method and converted to unilamellar liposomes by extrusion.
Results. With transdermal iontophoresis, therapeutically relevant amounts of propranolol (83.78 ± 7.4 ng/ml) were delivered within an hour and lasted for up to 4 h. Cmax (185.1 ± 56.8 ng/ml) was reached at hour 3. A significantly higher amount (p < 0.05) of sotalol HCl was delivered compared to other -blockers. There was no significant difference in the S/R ratio of AUC0-t for enantiomers after both intravenous and transdermal delivery. Skin irritation was significantly reduced (p < 0.05) when a liposomal formulation of the propranolol base was used rather than the base itself.
Conclusions. The comparative pharmacokinetics of intravenous and transdermal iontophoretic delivery of five -blockers in hairless rats was established. It was shown that there is no stereoselective permeation. 相似文献
39.
A comprehensive view of sex-specific issues related to cardiovascular disease 总被引:7,自引:3,他引:7 下载免费PDF全文
Louise Pilote Kaberi Dasgupta Veena Guru Karin H. Humphries Jennifer McGrath Colleen Norris Doreen Rabi Johanne Tremblay Arsham Alamian Tracie Barnett Jafna Cox William Amin Ghali Sherry Grace Pavel Hamet Teresa Ho Susan Kirkland Marie Lambert Danielle Libersan Jennifer O'Loughlin Gilles Paradis Milan Petrovich Vicky Tagalakis 《Canadian Medical Association journal》2007,176(6):S1-S44
Cardiovascular disease (CVD) is the leading cause of mortality in women. In fact, CVD is responsible for a third of all deaths of women worldwide and half of all deaths of women over 50 years of age in developing countries. The prevalence of CVD risk factor precursors is increasing in children. Retrospective analyses suggest that there are some clinically relevant differences between women and men in terms of prevalence, presentation, management and outcomes of the disease, but little is known about why CVD affects women and men differently. For instance, women with diabetes have a significantly higher CVD mortality rate than men with diabetes. Similarly, women with atrial fibrillation are at greater risk of stroke than men with atrial fibrillation. Historically, women have been underrepresented in clinical trials. The lack of good trial evidence concerning sex-specific outcomes has led to assumptions about CVD treatment in women, which in turn may have resulted in inadequate diagnoses and suboptimal management, greatly affecting outcomes. This knowledge gap may also explain why cardiovascular health in women is not improving as fast as that of men. Over the last decades, mortality rates in men have steadily declined, while those in women remained stable. It is also becoming increasingly evident that gender differences in cultural, behavioural, psychosocial and socioeconomic status are responsible, to various degrees, for the observed differences between women and men. However, the interaction between sex-and gender-related factors and CVD outcomes in women remains largely unknown. 相似文献
40.
The objective of this study is to determine the effect of various neutral liposomes on corneal and conjunctival permeability of didanosine (ddI), an antiviral drug. Multi-lamellar vesicles (MLVs), large unilamellar vesicles (LUVs), and sonicated multi-lamellar vesicles (SMLVs) encapsulating ddI (with trace quantities of 3HddI) were prepared using distearoyl phosphatidylcholine (DSPC), a neutral lipid. The liposomes contained 14C-cholesteryl oleate as a lipid tracer. Liposome formulations containing free and encapsulated drug (f + e) and those containing only encapsulated drug (e) of an equal quantity were compared with free drug in this study. The permeability studies were conducted in the mucosal to serosal direction across excised rabbit cornea and conjunctiva. The percent encapsulation of ddI in MLVs, LUVs, and SMLVs was 25.66 0.30, 26.56 0.57, and 19.41 0.30, respectively. The mean particle size of MLVs, LUVs, and SMLVs containingfree and encapsulated drug was 3058, 774, and 270 nm, respectively. With all liposome formulations tested, the percent uptake of lipid by tissues was higher compared to ddI uptake. While ddI permeated across the tissues, the lipid tracer did not permeate in detectable quantities.The SMLV(e) formulation was better than the SMLV(f + e) formulation with respect to initial flux and tissue uptake in both tissues and permeability across conjunctiva. In general, the permeability coefficient, initial flux, and tissue levels of ddI at the end of the transport study were lower in the presence of all liposome formulations compared to free drug. Thus, neutral liposomal encapsulation is not a suitable approach to enhance the corneal or conjunctival transport or uptake of ddI. 相似文献