Evolution
Paul Pumpens in Single-Stranded RNA Phages, 2020
As mentioned briefly in the Some special features of the Qβ replicase enzyme section of Chapter 13, Sumper and Luce (1975) from Manfred Eigen's team offered strong evidence for a new type of the template-free de novo RNA synthesis, catalyzed by the Qβ replicase, in which truly self-replicating RNA structures as long as 200 nucleotides were produced. These sequences were not homopolymeric or strictly alternating, and they were adapted to the environmental conditions applied during their generation. Qβ enzyme contamination by traces of RNA templates was ruled out by the following arguments: (i) additional purification steps did not eliminate this phenomenon, (ii) the lag phase was lengthened to several hours by lowering substrate or enzyme concentration, (iii) different enzyme concentrations led to RNA species of completely different primary structure, (iv) addition of oligonucleotides or preincubation with only three nucleoside triphosphates affected the final RNA sequence, and (v) manipulation of conditions during the lag phase resulted in the production of RNA structures that were adapted to the particular incubation conditions applied, e.g., RNA resistant to nuclease attack or resistant to inhibitors or even RNAs “addicted to the drug,” in the sense that they only replicate in the presence of a drug like acridine orange (Sumper and Luce 1975).
Collagen Fibrillogenesis
Marcel E. Nimni in Collagen, 1988
The two model systems are not mutually exclusive, and, in fact, it is likely that both nucleation and growth processes and fibril or intermediate aggregate association can occur simultaneously, with solution conditions, path, etc. determining both the overall rate of fibrillogenesis and the morphology of the final product. A heuristic model, which will be of value for the following discussion, is presented in Figure 6. In this model the lag phase is strictly defined as one requiring an intramolecular event, or conformational transition,6,7,48,71 governed by rate constant k1. Once this transition occurs, 4D dimer formation takes place, but this structure either dissociates or very rapidly proceeds (k2 ≫ k1) to the critical size n* to sustain growth. Any condition which favors stabilized or preformed dimer or higher aggregates will shorten the lag phase. Depending upon conditions, growth proceeds either by addition of monomers or interaction of aggregates, again further influenced in path as to lengthwise or lateral growth rates. The D-periodic structures which form then aggregate to form larger size, mature D-periodic structures. Because of the specific interaction areas created by the telopeptide regions after association of the n* aggregate, as well as in its formation, both lag phase kinetics and growth pathways may be affected by the integrity of the telopeptides.
Biology of microbes
Philip A. Geis in Cosmetic Microbiology, 2006
When microorganisms are first introduced into fresh media, no immediate increase in cell numbers occurs. This is referred to as the lag phase. All cultures go through a lag phase if the medium is different from the one the organisms were transferred from or when the organisms are not in exponential phase. The lag phase may be the result when cells are old and depleted of ATP or it may be due to essential cofactors or ribosomes that must be synthesized before binary fission can occur. The lag phase is especially long if an inoculum is from an old culture. Sometimes the lag phase can be avoided entirely if an inoculum is transferred during log phase into a fresh medium of the same composition.
Endometrial development during the transition to menopause: preliminary associations with follicular dynamics
Published in Climacteric, 2020
A. Baerwald, H. Vanden Brink, C. Lee, C. Hunter, K. Turner, D. Chizen
Thirty women were recruited in the following manner: MRA (18–35 years; n = 10) and ARA (45–55 years; n = 20). Inclusion criteria included: a normal complete blood count; and normal serum thyroid-stimulating hormone, prolactin, and β-human chorionic gonadotropin. Women aged 18–35 years must have had a history of regular menstrual cycles in order to participate. Women aged 45–55 years must have experienced no more than 12 months of amenorrhea to be eligible. Exclusion criteria included: body mass index <18 or >35, use of any hormone therapies within 2 months of enrollment, current smokers, women with documented ovarian failure and/or currently diagnosed infertility of unexplained or female origin, dysfunctional uterine bleeding, medical conditions or use of medications known or suspected to interfere with reproductive function, presence of only one ovary, inability to visualize the ovaries ultrasonographically, pregnancy, lactation within the last 12 months, surgery during the course of the study, and/or participation in an investigational drug trial within 30 days of study participation. Data from women with ovulatory cycles were included in our analyses (n = 26). Women were excluded from analyses due to anovulatory cycles (n = 2) and development of lag phases of follicle development (n = 2). A lag phase was defined as a period of no follicular development ≥6 mm for more than 20 days from menses or ovulation (i.e. based on 2 standard deviations above the mean follicular or luteal phase length).
Exenatide-loaded inside-porous poly(lactic-co-glycolic acid) microspheres as a long-acting drug delivery system with improved release characteristics
Published in Drug Delivery, 2020
Junqiu Zhai, Zhanlun Ou, Liuting Zhong, Yu-e Wang, Li-Ping Cao, Shixia Guan
In this study, the EXT-loaded PLGA microspheres were effectively fabricated by W1/O/W2 emulsion microfluidic method. The effects of various polymer type, PLGA concentration, proportion of drug and oil phase, and especially the porogen concentration on the release behaviors of EXT-PMS were studied in the system. Characterizations demonstrated the internal large pores and the external thin layer structure of EXT-PMS. Both in vitro and in vivo experiments validated the ability of our formulation of EXT-PMS to release drugs rapidly in the initial phase and to maintain effective concentration without delay-release for 30 days. The resulting inside-porous microspheres could sustain the release of EXT and offer the dual-advantage of (i) absence of a lag phase and (ii) low burst release. To the best of our knowledge, this is the first work to improve the release profile of EXT by inside-porous PLGA microspheres. Our method indicates the great potential for these inside-porous microspheres in the development of long-acting drug delivery systems with reasonable release profiles for various drugs.
Engineered PLGA microspheres for extended release of brexpiprazole: in vitro and in vivo studies
Published in Drug Development and Industrial Pharmacy, 2021
Bangqing Wu, Lijun Wu, Yingju He, Zongning Yin, Li Deng
In summary, brexpiprazole loaded PLGA microspheres with spherical and porous structures were successfully prepared via a facile O/W emulsion-solvent evaporation method. In vitro brexpiprazole release from PLGA microsphere formulations showed a triphasic release profile, with an initial burst release, followed by a lag phase and then a secondary zero-order release phase. In vivo, these microspheres exhibited a biphasic release curve with an initial burst followed by a clear zero-order release phase. The lack of a lag phase in vivo might be the result of complex internal environment. In addition, the release rate of the drug in vivo was faster. Both in vitro and in vivo release data suggest that the microspheres have controlled and sustained release potential, which offers an alternative treatment option for patients with schizophrenia.
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