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1.
报告介绍了2013 年第4 季度各国获得简化新药申请(ANDA)批准、《药品管理档案》(DMF)申报、遭遇专利挑战的情况,以及生物仿制药市场、仿制药行业交易和相关仿制药企业的进展。 相似文献
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S. C. Thomson 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1998,353(1375):1595-1606
Speakman and co-workers suggested the diurnal Samoan flying fox, Pteropus samoensis, may be at risk of hyperthermia when flying during the day, particularly at high levels of insolation. We monitored activity of this bat and climate simultaneously at two different sites and four times of year in American Samoa. Flight activity varied significantly with time of day, between days, study sites and seasons. Out of the six data sets collected, the four with the highest mean levels of insolation showed a significant decrease in bat numbers with increasing temperature and sunlight. When each individual activity count was directly compared to the predictions of Speakman and co-workers'' biophysical model, 85 to 95% of bat flight activity was found to be in conditions the model suggested would not pose a risk of hyperthermia. This supports the suggestion that in extreme conditions the animals would not fly as they risked overheating. The 5 to 15% of counts in which animals were seen to fly in conditions the model predicted they should not may be explained by erroneous assumptions underlying the model predictions. 相似文献
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The protection afforded by phosphocitrate, a phosphorylated polycarboxylic acid, against crystal-induced membrane damage to polymorphonuclear leukocytes was studied in vitro. Membranolysis was assessed by nitro blue tetrazolium salt reduction, lactate dehydrogenase release, and scanning electron microscopy. Phosphocitrate protected strongly against hydroxyapatite crystal-induced damage, an action attributable to crystal surface binding of phosphocitrate rather than to the membrane. The ability of phosphocitrate to prevent hydroxyapatite crystallization, together with its membrane protective effect against preformed crystals, would suggest that the compound might have a useful future role against crystal-induced arthropathies. 相似文献
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A spectrum of changes occurs in the function of the gastrointestinal tract throughout the life of the animal. With aging, there is a decline towards newborn levels of the villus surface area and brush border membrane markers, but the absorption of some nutrients continues to increase (such as glucose and vitamin), whereas the absorption of some nutrients falls (such as cholesterol) and fatty acids). Clearly there is a distinction between age-related alterations in intestinal form and function, and some of the enzyme- or carrier-mediated changes are substrate specific. With aging, the structure and brush border membrane composition of the intestine tends to regress towards newborn levels. It remains to be clarified whether these changes are a benefit to the animal, whether they represent a degeneration of normal function, and whether these changes are the cause or the effect of various age-related alterations in metabolic and physiological function. 相似文献
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In 33 patients with an intersphincteric abscess continuous anal pain was the commonest symptom and a lump in the wall of the anal canal the commonest sign.The importance of this condition as a cause of persistent undiagnosed anal pain is stressed. 相似文献
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Using stereological procedures, a detailed analysis was made from thin section electron micrographs of secreting and nonsecreting salt glands of Frankenia grandifolia (Cham. and Schlecht) and Avicennia germinans (L.) Stem. In F. grandifolia secretory cells, vacuolar volume significantly decreased, while the volume of endoplasmic reticulum increased in secreting glands. Numerous minivacuoles were predominantly located along the periphery of secreting secretory cells, some in apparent fusion with the plasma membrane. No difference was found in mitochondrial volume in the secretory cells between secreting and nonsecreting glands. In A. germinans, there was a significant decrease in vacuolar volume in secreting secretory cells. The volume of the endoplasmic reticulum and mitochondria also increased in these cells. However, no evidence of mini-vacuolar fusion with the plasma membrane was observed. These results indicate that the physical process of secretion may differ between F. grandifolia and A. germinans; in both, however, the ultrastructural observations support the contention that specific structural parameters are correlated with the process of secretion. 相似文献
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C S Butler J M Charnock B Bennett H J Sears A J Reilly S J Ferguson C D Garner D J Lowe A J Thomson B C Berks D J Richardson 《Biochemistry》1999,38(28):9000-9012
The periplasmic nitrate reductase from Paracoccus denitrificans is a soluble two-subunit enzyme which binds two hemes (c-type), a [4Fe-4S] center, and a bis molybdopterin guanine dinucleotide cofactor (bis-MGD). A catalytic cycle for this enzyme is presented based on a study of these redox centers using electron paramagnetic resonance (EPR) and extended X-ray absorption fine structure (EXAFS) spectroscopies. The Mo(V) EPR signal of resting NAP (High g [resting]) has g(av) = 1.9898 is rhombic, exhibits low anisotropy, and is split by two weakly interacting protons which are not solvent-exchangeable. Addition of exogenous ligands to this resting state (e.g., nitrate, nitrite, azide) did not change the form of the signal. A distinct form of the High g Mo(V) signal, which has slightly lower anisotropy and higher rhombicity, was trapped during turnover of nitrate and may represent a catalytically relevant Mo(V) intermediate (High g [nitrate]). Mo K-edge EXAFS analysis was undertaken on the ferricyanide oxidized enzyme, a reduced sample frozen within 10 min of dithionite addition, and a nitrate-reoxidized form of the enzyme. The oxidized enzyme was fitted best as a di-oxo Mo(VI) species with 5 sulfur ligands (4 at 2. 43 A and 1 at 2.82 A), and the reduced form was fitted best as a mono-oxo Mo(IV) species with 3 sulfur ligands at 2.35 A. The addition of nitrate to the reduced enzyme resulted in reoxidation to a di-oxo Mo(VI) species similar to the resting enzyme. Prolonged incubation of NAP with dithionite in the absence of nitrate (i.e., nonturnover conditions) resulted in the formation of a species with a Mo(V) EPR signal that is quite distinct from the High g family and which has a g(av) = 1.973 (Low g [unsplit]). This signal resembles those of the mono-MGD xanthine oxidase family and is proposed to arise from an inactive form of the nitrate reductase in which the Mo(V) form is only coordinated by the dithiolene of one MGD. In samples of NAP that had been reduced with dithionite, treated with azide or cyanide, and then reoxidized with ferricyanide, two Mo(V) signals were detected with g(av) elevated compared to the High g signals. Kinetic analysis demonstrated that azide and cyanide displayed competitive and noncompetitive inhibition, respectively. EXAFS analysis of azide-treated samples show improvement to the fit when two nitrogens are included in the molybdenum coordination sphere at 2.52 A, suggesting that azide binds directly to Mo(IV). Based on these spectroscopic and kinetic data, models for Mo coordination during turnover have been proposed. 相似文献