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This study examined the application of previously characterized microparticles composed of hyaluronan (HA) and chitosan hydroglutamate (CH) as well as novel microparticles consisting of both polymers (HA/CH) to improve the nasal delivery of a model drug. The rabbit bioavailabilities of gentamicin incorporated in HA, CH, and HA/CH microparticles were increased 23-, 31-, and 42-fold, respectively, compared with the control intranasal solution of gentamicin, indicating that all test microparticles were retained for longer periods on the nasal mucosa of the rabbits as supported by previous in vitro dissolution as well as frog palate mucoadhesion studies, thereby improving drug absorption. The higher bioavailabilities of CH-based formulations (CH and HA/CH) suggest the penetration-enhancing effects of CH may also be partially responsible for the improvement. A model was developed, based on a glass impinger device, to deliver dry powder formulations reproducibly onto the surface of cultured cell monolayers. In vitro permeability and fluorescence microscopy studies on the tight junctions of the 16HBE14o- cell lines further confirmed the ability of CH-based formulations to enhance penetration. Furthermore, the in vitro absorption profile from cell culture studies was consistent with those determined from in vivo studies. The complementary effect from the mucoadhesive nature of HA coupled with the penetration-enhancing effects of CH makes the novel HA/CH formulation a promising nasal delivery system. 相似文献
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Franc-Christophe Baurens Stéphanie Bocs Mathieu Rouard Takashi Matsumoto Robert NG Miller Marguerite Rodier-Goud Didier MBéguié-A-MBéguié Nabila Yahiaoui 《BMC plant biology》2010,10(1):149
Background
Comparative sequence analysis of complex loci such as resistance gene analog clusters allows estimating the degree of sequence conservation and mechanisms of divergence at the intraspecies level. In banana (Musa sp.), two diploid wild species Musa acuminata (A genome) and Musa balbisiana (B genome) contribute to the polyploid genome of many cultivars. The M. balbisiana species is associated with vigour and tolerance to pests and disease and little is known on the genome structure and haplotype diversity within this species. Here, we compare two genomic sequences of 253 and 223 kb corresponding to two haplotypes of the RGA08 resistance gene analog locus in M. balbisiana "Pisang Klutuk Wulung" (PKW). 相似文献34.
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Samson Mani Katarzyna Szymańska Cyrille Cuenin David Zaridze Karen Balassiano Sheila CS Lima Elena Matos Alexander Daudt Sergio Koifman Victor Wunsch Filho Ana MB Menezes Maria Paula Curado Gilles Ferro Thomas Vaissière Bakary S Sylla Massimo Tommasino Luis Felipe Ribeiro Pinto Paolo Boffetta Pierre Hainaut Paul Brennan Zdenko Herceg 《Epigenetics》2012,7(3):270-277
Cancers of the upper aerodigestive tract (UADT) are common forms of malignancy associated with tobacco and alcohol exposures, although human papillomavirus and nutritional deficiency are also important risk factors. While somatically acquired DNA methylation changes have been associated with UADT cancers, what triggers these events and precise epigenetic targets are poorly understood. In this study, we applied quantitative profiling of DNA methylation states in a panel of cancer-associated genes to a case-control study of UADT cancers. Our analyses revealed a high frequency of aberrant hypermethylation of several genes, including MYOD1, CHRNA3 and MTHFR in UADT tumors, whereas CDKN2A was moderately hypermethylated. Among differentially methylated genes, we identified a new gene (the nicotinic acetycholine receptor gene) as target of aberrant hypermethylation in UADT cancers, suggesting that epigenetic deregulation of nicotinic acetycholine receptors in non-neuronal tissues may promote the development of UADT cancers. Importantly, we found that sex and age is strongly associated with the methylation states, whereas tobacco smoking and alcohol intake may also influence the methylation levels in specific genes. This study identifies aberrant DNA methylation patterns in UADT cancers and suggests a potential mechanism by which environmental factors may deregulate key cellular genes involved in tumor suppression and contribute to UADT cancers.Key words: DNA methylation, upper aerodigestive tract, cancer, risk factors, biomarkers 相似文献
36.
Vibeke Secher Dam Donna MB Boedtkjer Christian Aalkjaer Vladimir Matchkov 《Channels (Austin, Tex.)》2014,8(4):361-369
The presence of Ca2+-activated Cl– currents (ICl(Ca)) in vascular smooth muscle cells (VSMCs) is well established. ICl(Ca) are supposedly important for arterial contraction by linking changes in [Ca2+]i and membrane depolarization. Bestrophins and some members of the TMEM16 protein family were recently associated with ICl(Ca). Two distinct ICl(Ca) are characterized in VSMCs; the cGMP-dependent ICl(Ca) dependent upon bestrophin expression and the ‘classical’ Ca2+-activated Cl– current, which is bestrophin-independent. Interestingly, TMEM16A is essential for both the cGMP-dependent and the classical ICl(Ca). Furthermore, TMEM16A has a role in arterial contraction while bestrophins do not. TMEM16A’s role in the contractile response cannot be explained however only by a simple suppression of the depolarization by Cl– channels. It is suggested that TMEM16A expression modulates voltage-gated Ca2+ influx in a voltage-independent manner and recent studies also demonstrate a complex role of TMEM16A in modulating other membrane proteins. 相似文献
37.
Short bowel syndrome (SBS) occurs in patients fed total parenteral nutrition (TPN) after massive intestinal resection. TPN weaning is often associated with occlusion or sepsis. In the present study the intestinal biotope was investigated in young patients (n = 14) with massive intestinal resection and recurrent symptoms of sepsis or occlusion during enteral food introduction. They were treated by aminosides for a long term period. Ileal effluents were collected for enumerating bacteria. In some case, blood and rectal specimen were also collected. A few patients developed bacterial overgrowth (1), occlusion (1), sepsis (4), osteoarthritis (1) or pneumonia (1) during the survey. A drastic drop of bifidobacteria that was not prevented by human milk feeding was observed prior occlusion or respiratory infection. Detection of clostridial vegetative forms preceded sepsis and decrease in clostridia parallelled recovery. In conclusion, onset of symptoms was related with extreme imbalance of the ileal flora. Supplementation with bifidobacterial compounds that were well tolerated in two patients could be of interest in children with recurrent symptoms. 相似文献
38.
J. O'Grady MB ChB MRCP. S. Warrington MB BChir MA MRCP. M.J. Moti S. Bunting BSc. R. Flower BSc PhD. A.S.E. Fowle MD MRCP. E.A. Higgs BSc MSc. S. Moncada MD PhD. 《Prostaglandins & other lipid mediators》1980,19(2):319-332
Prostacyclin infused intravenously in human volunteers induces ex vivo inhibition of platelet aggregation, tachycardia and hypotension. The inhibition of platelet aggregation is obtained with slightly lower doses than those which exhibit cardiovascular effects.The cardiovascular effects disappeared within a few minutes after discontinuing the infusion of prostacyclin but the platelet effects were longer lasting.Prostacyclin did not have any effect on platelet count, platelet factor 3, accelerated partial thromboplastin time, prothrombin time, euglobulin clot lysis time, fibrinogen degradation products, blood glucose concentration or urine sodium potassium ratio. 相似文献
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