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1.
Microporous, poly(epsilon-caprolactone) (PCL) matrices were loaded with progesterone by precipitation casting using co-solutions of PCL and progesterone in acetone. Progesterone loadings up to 32% w/w were readily achieved by increasing the drug content of the starting PCL solution. The kinetics of steroid release in PBS at 37 degrees C over 10 days could be described effectively by a diffusional release model although the Korsmeyer-Peppas model indicated the involvement of multiple release phenomena. The diffusion rate constant (D) increased from 8 to 24 microg/mg matrix/day0.5 as the drug loading increased from 3.6 to 12.4% w/w. A total cumulative release of 75%-95% indicates the high efficiency of steroid delivery. Increasing the matrix density from 0.22 to 0.39 g/cm3, by increasing the starting PCL solution concentration, was less effective in changing drug release kinetics. Retention of anti-proliferative activity of released steroid was confirmed using cultures of breast cancer epithelial (MCF-7) cells. Progesterone released from PCL matrices into PBS at 37 degrees C over 14 days retarded the growth of MCF-7 cells by a factor of at least 3.5 compared with progesterone-free controls. These findings recommend further investigation of precipitation-cast PCL matrices for delivery of bioactive molecules such as anti-proliferative agents from implanted, inserted or topical devices. 相似文献
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INVOLVEMENT OF NON-NMDA AND NMDA RECEPTORS IN GLUTAMATE-INDUCED PRESSOR OR DEPRESSOR RESPONSES OF THE PONS AND MEDULLA 总被引:1,自引:0,他引:1
SY Chen WC Wu CJ Tseng JS Kuo CY Chai 《Clinical and experimental pharmacology & physiology》1997,24(1):46-56
1. Fifty-five intact and six baroreceptor denervated and vagotomized cats of either sex were anaesthetized intraperito-neally with urethane (400 mg/kg) and a-chloralose (40 mg/kg). Responses of the systemic arterial pressure (SAP), mean SAP (MSAP) and sympathetic vertebral nerve (VNA) and renal nerve activities (RNA) were recorded. 2. In intact animals, monosodium L-glutamate (Glu, 0.1 mol/L, 50 nL) was microinjected into pressor areas of the locus coeruleus (LC), gigantocellular tegmental field (GTF), rostral ventrolateral medulla (RVLM) and dorsomedial medulla (DM), and the depressor areas of caudal ventrolateral medulla (CVLM). The induced actions were compared before and after microinjection of either glutamate antagonists, glutamate diethylester (GDEE, 0.5 mol/L, 50–100nL), a competitive AMPA receptor blocker, or 2-amino-5-phosphonovaleric acid (D-AP5, 0.025 mol/L, 50–100 nL), a competitive N-methyl-D-aspartate (NMDA) receptor blocker. GDEE completely blocked the increases of SAP and VNA elicited from all pressor areas. D-AP5 only partially blocked the pressor but slightly blocked VNA and RNA responses from LC, GTF and DM, particularly those from RVLM. Neither GDEE nor D-AP5 blocked the depressor responses of SAP and two nerve activities elicited from CVLM. 3. In baroreceptor denervated animals, NMDA (2 mmol/L, 50–100 nL) and AMPA (0.2 mmol/L, 50–100 nL) were micro-injected into the same pressor areas of GTF, RVLM and DM and the depressor area of CVLM responsive to Glu activation (0.1 mol/L, 30 nL). In RVLM, DM and CVLM, the results of either NMDA or AMPA were similar to those induced by Glu. However, in GTF, microinjection of either NMDA or AMPA did not induce similar responses to Glu. This suggests that the nature of GTF may differ from RVLM and DM. 4. The above results suggest that the Glu-induced pressor responses from LC, GTF, DM and especially RVLM, are primarily mediated through AMPA receptors. The Glu-induced depressor responses from CVLM may not be predominantly mediated by either AMPA or NMDA receptors. 5. In both baroreceptor-intact and -denervated cats stimulation of the pressor areas often produced an increase of VNA and a decrease of RNA, while in the depressor CVLM decreased both VNA and RNA. The VNA, but not RNA were positively correlated with the pressor responses, while both VNA and RNA were positively correlated with the depressor responses. This may suggest that neurons of the sympathetic vertebral and renal nerves are topographically organized in the brain. 相似文献
4.
Hillmann JS; Mesgarzadeh M; Revesz G; Bonakdarpour A; Clancy M; Betz RR 《Radiology》1987,165(3):769-773
Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification. 相似文献
5.
Acute and chronic pharmacokinetics of asymmetrical doses of slow release choline theophyllinate in asthma. 下载免费PDF全文
S G Hibberd C Alveyn E J Coombes S T Holgate 《British journal of clinical pharmacology》1986,22(3):337-341
The day and night pharmacokinetics of assymetrical doses of slow release choline theophyllinate (Sabidal SR 270) were compared at day 1 and at day 4 of treatment when steady state had been achieved. Ten patients with chronic asthma were given oral choline theophyllinate 424 mg at 09.00 h and 848 mg at 21.00 h for 4 days. At regular intervals during day 1 and day 4 of treatment theophylline concentrations were measured in plasma and dried blood spots by fluorimmunoassay. Theophylline concentrations measured from dried blood spots were slightly lower than those in plasma, the difference remaining constant at all time points during day 1 and day 4 of treatment. On day 1 the mean peak plasma theophylline concentration was 5.4 +/- 1.0 (+/- s.e. mean) micrograms ml-1 4 h after the morning dose and 11.2 +/- 1.6 micrograms ml-1 4 h after the evening dose which were significantly (P less than 0.01) different. Similarly the areas under the plasma theophylline concentration-time curves at night were significantly (P less than 0.001) greater than those observed during the day. During day 4 mean peak plasma concentrations of theophylline after the morning and larger evening dose were 13.2 +/- 1.3 and 12.1 +/- 1.4 micrograms ml-1 respectively, which were not significantly different. No significant difference was observed between the areas under the plasma theophylline concentration-time curves during the day and at night. However the post-dose time to peak was significantly delayed at night (6 h) compared to the morning (2 h, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Serum ionic fluoride levels in haemodialysis and continuous ambulatory peritoneal dialysis patients 总被引:1,自引:1,他引:0
al-Wakeel JS; Mitwalli AH; Huraib S; al-Mohaya S; Abu-Aisha H; Chaudhary AR; al-Majed SA; Memon N 《Nephrology, dialysis, transplantation》1997,12(7):1420-1424
High serum fluoride (F-) in patients with chronic renal failure (CRF) and
end-stage renal disease (ESRD) is associated with risk of renal
osteodystrophy and other bone changes. This study was done to determine F-
in normal healthy controls and patients with ESRD on haemodialysis (HD) or
peritoneal dialysis (PD). Seventeen healthy controls (12 males, 5 females)
and 39 ESRD patients on dialysis (17 males, 22 females) were recruited in
the study in a community with 47.4 +/- 3.28 microM/l (range 44-51 microM/l)
of F- content in drinking water. Control subjects showed a mean serum F-
concentration of 1.08 +/- 0.350 microM/l. Males in control group showed
slightly higher F- levels (1.15 +/- 0.334, range 0.55-1.9 microM/l) than
females (0.92 +/- 0.370, range 0.6-1.5 microM/l). Mean serum F-
concentration did not correlate significantly with age and sex among
control subjects, whereas such correlation was observed in patients with
ESRD on dialysis. Mean serum F- concentration was significantly higher in
patients on dialysis (2.67 +/- 1.09, range 0.8-5.2 microM/l) than normal
controls. When grouped according to sex, the mean serum F- concentration in
males (3.05 +/- 1.04, range 1.8-5.2 microM/l) was significantly higher than
females (2.38 +/- 1.08, range 0.8-5.2 microM/l). When patients were grouped
according to age, it was observed that F- concentration was significantly
higher in patients with age groups 21-70 (2.86 +/- 1.05) than those with
age group 13-20 years (1.42 +/- 0.531). Thus F- concentration correlated
with age and sex, being higher in males and above 20 years. Despite
appreciable clearance of F- (39-90%) across the peritoneum, patients on
CAPD showed higher serum F- concentration than those on HD (3.1 +/- 1.97 vs
2.5 +/- 1.137 microM/l). Of the total 39 patients on dialysis 39% had their
serum F- concentration above 3.0 microM/l, posing the risk of renal
osteodystrophy.
相似文献
10.
Rupture of the distal biceps tendon: evaluation with MR imaging 总被引:2,自引:0,他引:2