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51.
Bupranolol is a promising candidate for transdermal drug delivery system (TDDS) development. The effect of permeation enhancers on the in vivo delivery and beta-blocking effect of reservoir type TDDS was studied in comparison with intravenous BPL in rabbits. The beta-blocking effect was quantified by measuring the inhibition of isoprenaline induced tachycardia in rabbits after BPL administration via transdermal and intravenous routes. The reservoir type TDDS containing a hydroxypropyl cellulose gel and polyethylene membrane was used as a control device. In comparison, the TDDS containing skin penetration enhancers, either 2-pyrrolidone or partially methylated beta cyclodextrin (PMbetaCD) were evaluated. The control device (no enhancer) produced about 52% inhibition of isoprenaline induced tachycardia at 2 h and the effect continued over 24 h application period, however, the devices with 2-pyrolidone or PMbetaCD produced about 85% inhibition of isoprenaline induced tachycardia at 3 h and the same effect continued over 24 h application period. Likewise, the AUC of these devices were significantly higher than that of control device. The intravenous bupranolol showed rapid decline in the pharmacodynamic effect with time indicating its rapid elimination. The in vivo delivery of bupranolol (as estimated by a mass balance study) from the devices made with pyrolidone or PMbetaCD was 3-fold higher than that of control. The results of this study strongly suggest that the penetration enhancers in the TDDS increased the in vivo delivery of BPL, thereby increased the beta-blocking activity of BPL by 50-60% higher than control, enabling the reduction of the TDDS patch size, accordingly. 相似文献
52.
The basement membrane microenvironment directs the normalization and survival of bioengineered human skin equivalents. 总被引:1,自引:0,他引:1
Nadav Segal Frank Andriani Lawrence Pfeiffer Padmaja Kamath Ning Lin Kapettu Satyamurthy Christophe Egles Jonathan A Garlick 《Matrix biology》2008,27(3):163-170
Epithelial-mesenchymal interactions promote the morphogenesis and homeostasis of human skin. However, the role of the basement membrane (BM) during this process is not well-understood. To directly study how BM proteins influence epidermal differentiation, survival and growth, we developed novel 3D human skin equivalents (HSEs). These tissues were generated by growing keratinocytes at an air-liquid interface on polycarbonate membranes coated with individual matrix proteins (Type I Collagen, Type IV Collagen or fibronectin) that were placed on contracted Type I Collagen gels populated with dermal fibroblasts. We found that only keratinocytes grown on membranes coated with the BM protein Type IV Collagen showed optimal tissue architecture that was similar to control tissues grown on de-epidermalized dermis (AlloDerm) that contained intact BM. In contrast, tissues grown on proteins not found in BM, such as fibronectin and Type I Collagen, demonstrated aberrant tissue architecture that was linked to a significant elevation in apoptosis and lower levels of proliferation of basal keratinocytes. While all tissues demonstrated a normalized, linear pattern of deposition of laminin 5, tissues grown on Type IV Collagen showed elevated expression of alpha6 integrin, Type IV Collagen and Type VII Collagen, suggesting induction of BM organization. Keratinocyte differentiation (Keratin 1 and filaggrin) was not dependent on the presence of BM proteins. Thus, Type IV Collagen acts as a critical microenvironmental factor in the BM that is needed to sustain keratinocyte growth and survival and to optimize epithelial architecture. 相似文献
53.
Statistical optimization of process variables for the large-scale production of Metarhizium anisopliae conidiospores in solid-state fermentation 总被引:1,自引:0,他引:1
Optimization of conidial production was achieved by response surface methodology (RSM), a powerful mathematical approach widely applied in the optimization of fermentation process, using the three substrates; rice, barley and sorghum at variable pH, moisture content and yeast extract concentrations. These three factors were found to be important, affecting Metarhizium anisopliae spore production. A 2(3) full factorial central composite design and RSM were applied to determine the optimal concentration of each variable. A second-order polynomial was determined by the multiple regression analysis of the experimental data. Moisture content of 75.68% for sorghum, 73.21% for barley and 22.34% for rice produced optimal results. Maximal conidial yield was recorded for rice at a pH of 7.01; at 7.06 for sorghum and at 6.76 for barley. 相似文献
54.
55.
Padmaja N. Kulkarni A. Huntley Blair Tarunendu Ghose Molly Mammen 《Cancer immunology, immunotherapy : CII》1985,19(3):211-214
Summary Methotrexate (MTX) was first conjugated to antibovine serum albumin IgG (antiBSA) or its F(ab)2 fragment to define conditions for retention of drug and antibody activity. With identical drug: protein molar ratios, incorporation in the F(ab)2 fragment was lower than in intact antiBSA, an observation consistent with analysis of the number of lysine residues (22 in F(ab)2 compared to 40 in antiBSA). In either case, up to approximately 10 mol MTX could be incorporated per mol protein, with recovery of 70% of the protein. At an incorporation ratio of 6 mol MTX per mol protein, MTX-antiBSA retained 100% of antibody activity and MTX-F(ab)2antiBSA retained 75%. MTX-antiBSA and MTX-F(ab)2antiBSA were equally potent in vitro inhibitors of dihydrofolate reductase. Conjugates prepared from antiEL4 IgG (AELG) and from F(ab)2AELG significantly increased survival in EL4 lymphoma-bearing mice compared with mice receiving equal amounts (5 mg MTX/kg) of free MTX, MTX linked to the F(ab)2 fragment of normal rabbit IgG, or a simple mixture of MTX and F(ab)2AELG. MTX-AELG at this dose level produced longer survival than MTX-F(ab)2AELG (0.005
2AELG MTX linked to the F(ab)2 fragment of AELG - MTX-F(ab)2antiBSA MTX linked to the F(ab)2 fragment of antiBSA - MTX-F(ab)2NRG MTX linked to the F(ab)2 fragment of NRG - MTX-NRG MTX linked to NRG - NHS N-hydroxysuccinimide - NRG normal rabbit IgG - PBS 0.01 M sodium phosphate (pH 7.1) containing 0.45 M sodium chloride - TAA tumor-associated antigen - t1/2 half-life 相似文献
56.
57.
Meena Rajesh Kumar Reddy Kanubothula Sitarami Gautam Ranjana Maddela Surender Reddy Attipalli Ramachandra Gudipalli Padmaja 《Photosynthesis research》2021,147(3):253-267
Photosynthesis Research - Heterosis is a phenomenon wherein F1 hybrid often displays phenotypic superiority and surpasses its parents in terms of growth and agronomic traits. Investigations on the... 相似文献
58.
Chung CH Kurien BT Mehta P Mhatre M Mou S Pye QN Stewart C West M Williamson KS Post J Liu L Wang R Hensley K 《Biochemistry》2007,46(11):3262-3269
Proteomic experiments were performed to identify novel glutathione (GSH) binding proteins expressed in the mammalian central nervous system. Bovine brain lysate was affinity purified using an immobilized glutathione-Sepharose column. Proteins that bound the immobilized glutathione were eluted with free glutathione and identified by one- and two-dimensional electrophoresis coupled with mass spectrometric analysis of tryptic fragments. Major proteins purified by this technique were glutathione S-transferase-mu (GST-mu) and GST-pi and lanthionine synthase C-like protein-1 (LanCL1). LanCL1 is a mammalian homologue of a prokaryotic enzyme responsible for the synthesis of thioether (lanthionine) cross-links within nascent polypeptide chains, yielding macrocyclic proteins with potent microbicidal activity. An antibody against LanCL1 was generated and applied to immunochemical studies of spinal cord tissue from SOD1G93A transgenic mice, a model for amyotrophic lateral sclerosis (ALS), wherein LanCL1 expression was found to be increased at presymptomatic stages of the disease. These results indicate LanCL1 is a glutathione binding protein possibly significant to neurodegenerative disease. 相似文献
59.
Jurre Y. Siegers Vijaykrishna Dhanasekaran Ruopeng Xie Yi-Mo Deng Sarika Patel Vanra Ieng Jean Moselen Heidi Peck Ammar Aziz Borann Sarr Savuth Chin Seng Heng Asheena Khalakdina Michael Kinzer Darapheak Chau Philomena Raftery Veasna Duong Ly Sovann Ian G. Barr Erik A. Karlsson 《Journal of virology》2021,95(24)
60.
Ion transport across phospholipid vesicles was studied by 7Li and 23Na-NMR using an aqueous anionic paramagnetic shift reagent, dysprosium nitrilotriacetate [Dy(NTA)2]3−, mediated by ionophores, lasalocid A and A23187. The intra- and extracellular 7Li and 23Na-NMR signals were well separated (20 Hz) at mM concentration of the shift reagent. The observed data on the rate constant for lithium transport across DPPC vesicles at various concentrations of the ionophores indicated that lasalocid A is a more efficient carrier for lithium ion compared with the sodium ion transport by this ionophore, while A23187 was not specific to either of the ions (Li or Na). ©1998 European Peptide Society and John Wiley & Sons, Ltd. 相似文献