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91.
M.J. García-Fernández N. Tabary B. Martel F. Cazaux A. Oliva P. Taboada A. Concheiro C. Alvarez-Lorenzo 《Carbohydrate polymers》2013
Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, β- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks. 相似文献
92.
Roemer T Jiang B Davison J Ketela T Veillette K Breton A Tandia F Linteau A Sillaots S Marta C Martel N Veronneau S Lemieux S Kauffman S Becker J Storms R Boone C Bussey H 《Molecular microbiology》2003,50(1):167-181
Candida albicans is the primary fungal pathogen of humans. Despite the need for novel drugs to combat fungal infections [Sobel, J.D. (2000) Clin Infectious Dis 30: 652], antifungal drug discovery is currently limited by both the availability of suitable drug targets and assays to screen corresponding targets. A functional genomics approach based on the diploid C. albicans genome sequence, termed GRACETM (gene replacement and conditional expression), was used to assess gene essentiality through a combination of gene replacement and conditional gene expression. In a systematic application of this approach, we identify 567 essential genes in C. albicans. Interestingly, evaluating the conditional phenotype of all identifiable C. albicans homologues of the Saccharomyces cerevisiae essential gene set [Giaever, G., Chu, A.M., Ni, L., Connelly, C., Riles, L., Veronneau, S., et al. (2002) Nature 418: 387-391] by GRACE revealed only 61% to be essential in C. albicans, emphasizing the importance of performing such studies directly within the pathogen. Construction of this conditional mutant strain collection facilitates large-scale examination of terminal phenotypes of essential genes. This information enables preferred drug targets to be selected from the C. albicans essential gene set by phenotypic information derived both in vitro, such as cidal versus static terminal phenotypes, as well as in vivo through virulence studies using conditional strains in an animal model of infection. In addition, the combination of phenotypic and bioinformatic analyses further improves drug target selection from the C. albicans essential gene set, and their respective conditional mutant strains may be directly used as sensitive whole-cell assays for drug screening. 相似文献
93.
Poncet V Martel E Allouis S Devos M Lamy F Sarr A Robert T 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2002,104(6-7):965-975
Comparative mapping of Quantitative trait loci (QTLs) involved in domestication of adaptative syndrome traits of pearl millet was realized at the intra-specific level using two F(2) populations derived from domesticated ( Pennisetum glaucum ssp. glaucum) x wild ( Pennisetum glaucum ssp. monodii) crosses. The two domesticated parents analyzed differ in their geographical origins, agronomic characteristics and life cycles. In both populations, two regions of the genome were identified on linkage groups 6 and 7, that controlled most of the key morphological differences. The importance of these two linkage groups reveals their central role both in the developmental control of spikelet structure and in the domestication process of this crop. In contrast, QTLs involved in traits that are components of yield and measure differences in resource allocation (such as the shape of the spike, the number of spikes per plant and plant height) show a low level of correspondence among our two crosses. The results of the comparative mapping between cereals, although preliminary, reveal that genes involved in seed-shattering could correspond in maize, rice and sorghum. The evolutionary significance of our results, and especially the relationships between genome organization and cereal domestication, are discussed. The potential use of these results in pearl millet genetic-resources enhancement are presented. 相似文献
94.
Molecular dynamics simulation of cytochrome c3: studying the reduction processes using free energy calculations. 下载免费PDF全文
The tetraheme cytochrome c3 from Desulfovibrio vulgaris Hildenborough is studied using molecular dynamics simulation studies in explicit solvent. The high heme content of the protein, which has its core almost entirely made up of c-type heme, presents specific problems in the simulation. Instability in the structure is observed in long simulations above 1 ns, something that does not occur in a monoheme cytochrome, suggesting problems in heme parametrization. Given these stability problems, a partially restrained model, which avoids destruction of the structure, was created with the objective of performing free energy calculations of heme reduction, studies that require long simulations. With this model, the free energy of reduction of each individual heme was calculated. A correction in the long-range electrostatic interactions of charge groups belonging to the redox centers had to be made in order to make the system physically meaningful. Correlation is obtained between the calculated free energies and the experimental data for three of four hemes. However, the relative scale of the calculated energies is different from the scale of the experimental free energies. Reasons for this are discussed. In addition to the free energy calculations, this model allows the study of conformational changes upon reduction. Even if the precise details of the structural changes that take place in this system upon individual heme reduction are probably out of the reach of this study, it appears that these structural changes are small, similarly to what is observed for other redox proteins. This does not mean that their effect is minor, and one example is the conformational change observed in propionate D from heme I when heme II becomes reduced. A motion of this kind could be the basis of the experimentally observed cooperativity effects between heme reduction, namely positive cooperativity. 相似文献
95.
Andrea Barbi Tess Goessens Diederik Strubbe Arne Deknock Robby Van Leeuwenberg Niels De Troyer Elin Verbrugghe Mark Greener Siegrid De Baere Luc Lens Peter Goethals An Martel Siska Croubels Frank Pasmans 《Ecology letters》2023,26(2):313-322
The sixth mass extinction is a consequence of complex interplay between multiple stressors with negative impact on biodiversity. We here examine the interaction between two globally widespread anthropogenic drivers of amphibian declines: the fungal disease chytridiomycosis and antifungal use in agriculture. Field monitoring of 26 amphibian ponds in an agricultural landscape shows widespread occurrence of triazole fungicides in the water column throughout the amphibian breeding season, together with a negative correlation between early season application of epoxiconazole and the prevalence of chytrid infections in aquatic newts. While triazole concentrations in the ponds remained below those that inhibit growth of Batrachochytrium dendrobatidis, they bioaccumulated in the newts' skin up to tenfold, resulting in cutaneous growth-suppressing concentrations. As such, a concentration of epoxiconazole, 10 times below that needed to inhibit fungal growth, prevented chytrid infection in anuran tadpoles. The widespread presence of triazoles may thus alter chytrid dynamics in agricultural landscapes. 相似文献
96.
The social grooming of captive female rhesus monkeys: Effects of the births of their infants 总被引:1,自引:0,他引:1
Frances L. Martel Claire M. Nevison F. David G. Rayment Michael J. A. Simpson 《International journal of primatology》1994,15(4):555-572
We observed the grooming interactions of 13 female rhesus monkeys (Macaca mulatta)before and for 12 weeks after the births of their infants. Mothers groomed for similar amounts of time before and after the
birth of their infants, but after the birth, the grooming they directed to their infants may have been at the expense of that
directed to other partners. Lactating females did not receive more grooming from other females but were approached more often,
suggesting that they were more attractive. Mothers that groomed their infants most groomed others least, as if grooming time
was limited for each mother or as if she was trying to compensate for avoiding interactions with other partners. Mothers of
male infants groomed others more than mothers with female infants did, which might be due to mothers with daughters receiving
more aggression and therefore avoiding interaction. Experienced and high-ranking mothers groomed their newborn infants considerably
more than primiparous mothers did in the 24 hr following birth. Grooming was preferentially directed at close kin before the
births of the infants. Mothers tended to groom higher-ranked partners more than they were groomed by them, and they tended
to receive more grooming from lower-ranked partners than they gave, as suggested in models of rank attractiveness. 相似文献
97.
Martel C Picard S Richard V Bélanger A Labrie C Labrie F 《The Journal of steroid biochemistry and molecular biology》2000,74(1-2):45-56
Some undesirable effects are associated with chronic estrogen and progestin administration used to prevent bone loss in postmenopausal women, thus leading to poor compliance and the need for improved therapeutic and preventive agents. We have thus studied the ability of the new antiestrogen EM-800 (SCH 57050) to prevent bone loss and lower serum cholesterol levels and compared its effects with those of raloxifene. Ovariectomized (OVX) female rats were treated by oral gavage for 37 weeks with increasing daily doses (0.01, 0.03, 0.1, 0. 3 or 1 mg/kg) of EM-800 or raloxifene. At 35 weeks after OVX, lumbar spine bone mineral density (BMD) was 19% lower than in intact animals (P<0.01), while the OVX animals given EM-800 or raloxifene had 90-93 and 85-90%, respectively, of the BMD values observed in intact rats. Similar effects were observed on femoral BMD. Bone histomorphometry measurements were performed on proximal tibia. At the 0.01 mg/kg dose, EM-800 prevented the effect of OVX on TBV by 34% (P<0.01), while raloxifene had no detectable effect. Treatment with 1 mg/kg EM-800 and raloxifene resulted in, respectively, 68% (P<0.01) and 64% (P<0.01) prevention of the OVX-induced decrease in TBV. In addition, the administration of 0.01 and 0.03 mg/kg EM-800 caused, respectively, 54% (P<0.01) and 56% (P<0.01) inhibitions of serum cholesterol levels, while raloxifene administered at the same doses caused, respectively, 24% (P<0.01) and 41% (P<0.01) decreases of the value of the same parameter. At the highest doses used (0.1-1 mg/kg), both compounds lowered serum cholesterol levels by approximately 65% (P<0.01). No stimulatory effect of EM-800 was observed on the endometrial epithelial cells at doses up to 1 mg/kg, while hypertrophy of uterine epithelium was observed with raloxifene. EM-800 and raloxifene achieve the same degree of effectiveness on bone and serum cholesterol at higher doses, but EM-800 is at least three to ten times more potent than raloxifene at lower concentrations and has no stimulatory effect on uterine epithelium. The present data show the potent effect of EM-800 preventing bone loss and lower serum cholesterol levels without the negative effect on the endometrium, thus suggesting the particular interest of this new fully tissue-specific selective estrogen receptor modulator. 相似文献
98.
Stepanović S Dakić I Martel A Vaneechoutte M Morrison D Shittu A Jezek P Decostere A Devriese LA Haesebrouck F 《Systematic and applied microbiology》2005,28(4):353-357
Members of the Staphylococcus sciuri group (S. sciuri, S. lentus, and S. vitulinus) are coagulase-negative, novobiocin-resistant staphylococci that could be distinguished from other staphylococci on the basis of positive oxidase activity. In the present study, a scheme based on conventional methods and utilization of various carbohydrates was evaluated for the identification of oxidase-positive staphylococci, and validated using two molecular techniques. Of the 173 oxidase-positive staphylococcal tested strains, 161 were identified as S. sciuri, 9 as S. lentus, 2 as S. vitulinus, and one as S. fleurettii by our scheme. The level of agreement with tRNA intergenic length polymorphism analysis (tDNA-PCR) was high (97.5-100% correlation). The accuracy and ease of use of this protocol suggest that it may be useful and valuable in microbiological laboratories for the identification of members of this group. 相似文献
99.
Gauthier S Cloutier J Dory YL Favre A Mailhot J Ouellet C Schwerdtfeger A Mérand Y Martel C Simard J Labrie F 《Journal of enzyme inhibition and medicinal chemistry》2005,20(2):165-177
EM-652 (acolbifene) analogs have been synthesized as selective estrogen receptor modulators. Substitution on the nitrogen atom of these 2H-1-benzopyran derivatives has been studied for its influence on antiestrogenic activity. Binding to the rat estrogen receptor, inhibition of estradiol-stimulated proliferation of T-47D breast cancer cells, as well as antiuterotrophic and uterotrophic activities in ovariectomized mice have been evaluated. 2H-1-Benzopyran 1b (EM-343, racemic form of EM-652), which contains a piperidine ring, shows the best pharmacological profile; RBA = 380, IC50 value = 0.110 nM (in T-47D cells), as well as 63% and 84% antiuterotrophic inhibitions at the 7.5 and 75 nmol doses, respectively. 相似文献
100.
BACKGROUND: Endometrial polyps (EMPs) are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1) to investigate the age-group in which EMP are most commonly encountered 2) to document the age-group in which EMP are most commonly associated with malignancies 3) To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4) To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data. PATIENTS AND METHODS: All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986-1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof) of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups. RESULTS: We identified 513 EMPs, of which 209 (41%) were from biopsy specimens and 304 (59%) from hysterectomy specimens. Sixty six (13%) of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5%) of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32%) of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p < 0.001). The most common histologic type of malignancy was endometrioid adenocarcinoma. CONCLUSIONS: EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice. Additional studies are needed to address the histological features and immunohistochemical profiles in the context of association between endometrioid and high-grade endometrial carcinoma and endometrial polyps. 相似文献