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11.
Xiaoyu Yang Wei Xu Svetlana Dukleska Sabrina Benchaar Selina Mengisen Valentyn Antochshuk Jason Cheung Leslie Mann Zulfia Babadjanova Jason Rowand Rico Gunawan Alexander McCampbell Maribel Beaumont David Meininger Daisy Richardson Alexandre Ambrogelly 《MABS-AUSTIN》2013,5(5):787-794
Monoclonal antibodies constitute a robust class of therapeutic proteins. Their stability, resistance to stress conditions and high solubility have allowed the successful development and commercialization of over 40 antibody-based drugs. Although mAbs enjoy a relatively high probability of success compared with other therapeutic proteins, examples of projects that are suspended due to the instability of the molecule are not uncommon. Developability assessment studies have therefore been devised to identify early during process development problems associated with stability, solubility that is insufficient to meet expected dosing or sensitivity to stress. This set of experiments includes short-term stability studies at 2−8 þC, 25 þC and 40 þC, freeze-thaw studies, limited forced degradation studies and determination of the viscosity of high concentration samples. We present here three case studies reflecting three typical outcomes: (1) no major or unexpected degradation is found and the study results are used to inform early identification of degradation pathways and potential critical quality attributes within the Quality by Design framework defined by US Food and Drug Administration guidance documents; (2) identification of specific degradation pathway(s) that do not affect potency of the molecule, with subsequent definition of proper process control and formulation strategies; and (3) identification of degradation that affects potency, resulting in program termination and reallocation of resources. 相似文献
12.
Eleftherios I. Paschalis James Chodosh Ralph A. Sperling Borja Salvador-Culla Claes Dohlman 《PloS one》2013,8(6)
Purpose
To present a novel design of an implantable glaucoma valve based on ferrofluidic nanoparticles and to compare it with a well-established FDA approved valve.Setting
Massachusetts Eye & Ear Infirmary, Boston, USA.Methods
A glaucoma valve was designed using soft lithography techniques utilizing a water-immiscible magnetic fluid (ferrofluid) as a pressure-sensitive barrier to aqueous flow. Two rare earth micro magnets were used to calibrate the opening and closing pressure. In-vitro flow measurements were performed to characterize the valve and to compare it to Ahmed™ glaucoma valve. The reliability and predictability of the new valve was verified by pressure/flow measurements over a period of three months and X-ray diffraction (XRD) analysis over a period of eight weeks. In vivo assessment was performed in three rabbits.Results
In the in vitro experiments, the opening and closing pressures of the valve were 10 and 7 mmHg, respectively. The measured flow/pressure response was linearly proportional and reproducible over a period of three months (1.8 µl/min at 12 mmHg; 4.3 µl/min at 16 mmHg; 7.6 µl/min at 21 mmHg). X-ray diffraction analysis did not show oxidization of the ferrofluid when exposed to water or air. Preliminary in vivo results suggest that the valve is biocompatible and can control the intraocular pressure in rabbits.Conclusions
The proposed valve utilizes ferrofluid as passive, tunable constriction element to provide highly predictable opening and closing pressures while maintaining ocular tone. The ferrofluid maintained its magnetic properties in the aqueous environment and provided linear flow to pressure response. Our in-vitro tests showed reliable and reproducible results over a study period of three months. Preliminary in-vivo results were very promising and currently more thorough investigation of this device is underway. 相似文献13.
14.
Marco Savioli Lorenzo Antonelli Gianfranco Bocchinfuso Francesca Cavalieri Rita Cimino Emanuela Gatto Ernesto Placidi Julio Raul Fernandez Masso Hilda Garay Perez Hector Santana Maribel Guerra-Vallespi Mariano Venanzi 《Journal of peptide science》2022,28(1):e3356
Synthetic therapeutic peptides (STP) are intensively studied as new-generation drugs, characterized by high purity, biocompatibility, selectivity and stereochemical control. However, most of the studies are focussed on the bioactivity of STP without considering how the formulation actually used for therapy administration could alter the physico-chemical properties of the active principle. The aggregation properties of a 20-mer STP (Ac-His-Ala-Arg-Ile-Lys-D-Pro-Thr-Phe-Arg-Arg-D-Leu-Lys-Trp-Lys-Tyr-Lys-Gly-Lys-Phe-Trp-NH2), showing antitumor activity, were investigated by optical spectroscopy and atomic force microscopy imaging, as itself (CIGB552) and in its therapeutic formulation (CIGB552TF). It has found that the therapeutic formulation deeply affects the aggregation properties of the investigated peptide and the morphology of the aggregates formed on mica by deposition of CIGB552 and CIGB552TF millimolar solutions. Molecular dynamics simulations studied the first steps of CIGB552 aggregation under physiological ionic strength conditions (NaCl 150 mM), showing that peptide oligomers, from dimers to tetramers, are preferentially formed in this environment. Interestingly, cell viability assays performed on H-460 cell lines indicate a major antiproliferative activity of the peptide in its therapeutic formulation with respect to the peptide aqueous solution. 相似文献
15.
16.
Genetic diversity, genetic relationship, identification and population structure of 120 Aeromonas strains (including Aer. hydrophila, Aer. bestiarum, Aer. salmonicida and Aer. popoffii) isolated from various sources were studied by analysis of 15 genetic loci by multilocus enzyme electrophoresis (MLEE). All 15 loci were polymorphic, with an average of 9.4 alleles per locus and a mean genetic diversity (H) of 0.64. Cluster analysis defined at H < or = 0.7 differentiated most of the taxa analysed except the Aer. popoffii and Aer. bestiarum strains, which showed a close genetic relationship. Allelic frequencies of five loci (EST1, HEX, IDH, LDH1 and MDH) identified 94% of the strains. The index of association (IA) for the total sample was 2.38 and IA values calculated for the different populations were always significantly different from zero. These results suggest that the population structure of this Aeromonas sample is strongly clonal, confirm the taxonomic status of the analysed species in population genetics terms, and show the usefulness of MLEE for identifying Aeromonas species. 相似文献
17.
Ajith?R?Vancha Suman?Govindaraju Kishore?VL?Parsa Madhuri?Jasti Maribel?González-García Rafael?P?BallesteroEmail author 《BMC biotechnology》2004,4(1):23
Background
Several cell lines and primary cultures benefit from the use of positively charged extracellular matrix proteins or polymers that enhance their ability to attach to culture plates. Polyethyleneimine is a positively charged polymer that has gained recent attention as a transfection reagent. A less known use of this cationic polymer as an attachment factor was explored with several cell lines. 相似文献18.
Portbury AL Chandra R Groelle M McMillian MK Elias A Herlong JR Rios M Roffler-Tarlov S Chikaraishi DM 《American journal of physiology. Heart and circulatory physiology》2003,284(6):H2069-H2077
Mice lacking catecholamines die before birth, some with cardiovascular abnormalities. To investigate the role of catecholamines in development, embryonic day 12.5 (E12.5) fetuses were cultured and heart rate monitored. Under optimal oxygenation, wild-type and catecholamine-deficient fetuses had the same initial heart rate (200-220 beats/min), which decreased by 15% in wild-type fetuses during 50 min of culture. During the same culture period, catecholamine-deficient fetuses dropped their heart rate by 35%. Hypoxia reduced heart rate of wild-type fetuses by 35-40% in culture and by 20% in utero, assessed by echocardiography. However, catecholamine-deficient fetuses exhibited greater hypoxia-induced bradycardia, reducing their heart rate by 70-75% in culture. Isoproterenol, a beta-adrenergic receptor (beta-AR) agonist, reversed this extreme bradycardia, restoring the rate of catecholamine-deficient fetuses to that of nonmutant siblings. Moreover, isoproterenol rescued 100% of catecholamine-deficient pups to birth in a dose-dependent, stereo-specific manner when administered in the dam's drinking water. An alpha-AR agonist was without effect. When wild-type fetuses were cultured with adrenoreceptor antagonists to create pharmacological nulls, blockade of alpha-ARs with 10 microM phentolamine or beta-ARs with 10 microM bupranolol alone or in combination did not reduce heart rate under optimal oxygenation. However, when combined with hypoxia, beta-AR blockade reduced heart rate by 35%. In contrast, the muscarinic blocker atropine and the alpha-AR antagonist phentolamine had no effect. These data suggest that beta-ARs mediate survival in vivo and regulate heart rate in culture. We hypothesize that norepinephrine, acting through beta-ARs, maintains fetal heart rate during periods of transient hypoxia that occur throughout gestation, and that catecholamine-deficient fetuses die because they cannot withstand hypoxia-induced bradycardia. 相似文献
19.
The effects of light intensity, pH, temperature, and UV irradiation on the photosynthetic rate of Prochloron isolated from the ascidian host Lissoclinum patella, collected from Palau, were examined. Photosynthesis increased with light intensity with saturation at 500 μmol/m2 per second. It was maximum at pH 8 to 9 but almost completely suppressed below pH 7. The optimum temperature was 35° to 40°C,
but the photosynthesis was absent at ≤20°C and at 45°C. It was recovered when the symbiont was transferred from 1 hour of
incubation at ≤20°C to 35°C but not when transferred from incubation at 45°C. Ultraviolet irradiation severely inhibited the
photosynthesis of Prochloron in isolation but not in vivo. This protection was brought about by the tunic covering the ascidian colony, which contains
UV-absorbing mycosporine-like amino acids. These results indicate that the characteristic condition of the tropical marine
environment largely determines the ecological distribution of Prochloron, and the ascidian tunic protects the organism from UV radiation.
Received February 17, 2000; accepted August 8, 2000. 相似文献
20.
Vargas Cartagena L Sánchez E Vargas M Solórzano A Hernández F Iwasawa H Freer E 《Revista de biología tropical》2002,50(1):45-48
"Crespera" is an infectious disease of coffee plants that affects both the coffee production and the economy of the coffee producer countries. This disease affects morphologically the plant: long and narrow leaves with wavy borders and marginal necrosis; strong chlorosis results in drying of the leave, and leads to bad conditions of the plant. The internodes are short, producing the appearance of multiple sprouts in the axial sprout, the flowers can turn greenish, and the plant can present branches with severe symptoms, and branches without apparent symptoms at the same time. As a result, the coffee bean production decreases strikingly. The aim of this work was to determine the occurrence of the possible causative agent in the coffee plants using transmission electron microscopy. Normal and infected plants were compared looking at the leaves, central vein, lateral veins and petiole. It was determined that xylematic vessels show the presence of gram negative bacilliform bacteria (of thick-wavy walls), with dimensions of 0.3-0.5 micron diameter and 1-4 microns, length. The control plants did not show bacteria in the xylem. 相似文献