An Update on Maternal Hydration Strategies for Amniotic Fluid Improvement in Isolated Oligohydramnios and Normohydramnios: Evidence from a Systematic Review of Literature and Meta-Analysis

Objective

Several trials aimed at evaluating the efficacy of maternal hydration (MH) in increasing amniotic-fluid-volume (AFV) in pregnancies with isolated oligohydramnios or normohydramnos have been conducted. Unfortunately, no evidences support this intervention in routine-clinical-practice. The aim of this systematic-literature-review and meta-analysis was to collect all data regarding proposed strategies and their efficacy in relation to each clinical condition for which MH-therapy was performed with the aim of increasing amniotic-fluid (AF) and improving perinatal outcomes.

Materials and Methods

A systematic literature search was conducted in electronic-database MEDLINE, EMBASE, ScienceDirect and the Cochrane-Library in the time interval between 1991 and 2014. Following the identification of eligible trials, we estimated the methodological quality of each study (using QADAS-2) and clustered patients according to the following outcome measures: route of administration (oral versus intravenous versus combined), total daily dose of fluids administered (<2000 versus >2000), duration of hydration therapy: (1 day, >1 day but <1 week, >1 week), type of fluid administered (isotonic versus hypotonic versus combination).

Results

In isolated-oligohydramnios (IO), maternal oral hydration is more effective than intravenous hydration and hypotonic solutions superior to isotonic solutions. The improvement in AFV appears to be time-dependent rather than daily-dose dependent. Regarding normohydramnios pregnancies, all strategies seem equivalent though the administration of hypotonic-fluid appears to have a slightly greater effect than isotonic-fluid. Regarding perinatal outcomes, data is fragmentary and heterogeneous and does not allow us to define the real clinical utility of MH.

Conclusions

Available data suggests that MH may be a safe, well-tolerated and useful strategy to improve AFV especially in cases of IO. In view of the numerous obstetric situations in which a reduced AFV may pose a threat, particularly to the fetus, the possibility of increasing AFV with a simple and inexpensive practice like MH-therapy may have potential clinical applications. Considering the various strategies of maternal hydration implemented in the treatment of IO, better results were observed when treatment was based on a combination of intravenous (for a period of 1 day) and oral (for a period of at least 14 days) hypotonic fluids (≥2000ml).     

Albumin 3′untranslated region facilitates increased recombinant protein production from Chinese hamster ovary cells

Chinese hamster ovary (CHO) cells are used for recombinant protein production in the pharmaceutical industry but there is a need to improve expression levels. In the present work experiments were carried out to test the effectiveness of different 3′untranslated regions (3′UTRs) in promoting production of a naturally secreted luciferase. Seamless cloning was used to produce expression vectors in which Gaussia princeps luciferase coding sequences were linked to the human albumin, immunoglobulin or chymotrypsinogen 3′UTR. Stably transfected CHO cells expressing these constructs were selected. Luciferase activity in the culture medium was increased 2–3‐fold by replacing the endogenous 3′UTR with the albumin 3′UTR and decreased by replacement with immunoglobulin or chymotrypsinogen 3′UTR. Replacement of the native 3′UTR with the albumin 3′UTR led to a 10‐fold increase in luciferase mRNA levels. Deletion analysis of the albumin 3′UTR showed that loss of nucleotides 1–50, which removed an AU‐rich complex stem loop region, caused significant reductions in both luciferase protein expression and luciferase mRNA levels. The results suggest that recombinant protein expression and yield could be improved by the careful selection of appropriate 3′UTR sequences.     

Milestones in the development of photodynamic therapy and fluorescence diagnosis.

Many reviews on PDT have been published. This field is now so large, and embraces so many sub-specialties, from laser technology and optical penetration through diffusing media to a number of medical fields including dermatology, gastroenterology, ophthalmology, blood sterilization and treatment of microbial-viral diseases, that it is impossible to cover all aspects in a single review. Here, we will concentrate on a few basic aspects, all important for the route of development leading PDT to its present state: early work on hematoporphyrin and hematoporphyrin derivative, second and third generation photosensitizers, 5-aminolevulinic acid and its derivatives, oxygen and singlet oxygen, PDT effects on cell organelles, mutagenic potential, the basis for tumour selectivity, cell cooperativity, photochemical internalization, light penetration into tissue and the significance of oxygen depletion, photobleaching of photosensitizers, optimal light sources, effects on the immune system, and, finally, future trends.     

The Edge-Disjoint Path Problem on Random Graphs by Message-Passing

We present a message-passing algorithm to solve a series of edge-disjoint path problems on graphs based on the zero-temperature cavity equations. Edge-disjoint paths problems are important in the general context of routing, that can be defined by incorporating under a unique framework both traffic optimization and total path length minimization. The computation of the cavity equations can be performed efficiently by exploiting a mapping of a generalized edge-disjoint path problem on a star graph onto a weighted maximum matching problem. We perform extensive numerical simulations on random graphs of various types to test the performance both in terms of path length minimization and maximization of the number of accommodated paths. In addition, we test the performance on benchmark instances on various graphs by comparison with state-of-the-art algorithms and results found in the literature. Our message-passing algorithm always outperforms the others in terms of the number of accommodated paths when considering non trivial instances (otherwise it gives the same trivial results). Remarkably, the largest improvement in performance with respect to the other methods employed is found in the case of benchmarks with meshes, where the validity hypothesis behind message-passing is expected to worsen. In these cases, even though the exact message-passing equations do not converge, by introducing a reinforcement parameter to force convergence towards a sub optimal solution, we were able to always outperform the other algorithms with a peak of 27% performance improvement in terms of accommodated paths. On random graphs, we numerically observe two separated regimes: one in which all paths can be accommodated and one in which this is not possible. We also investigate the behavior of both the number of paths to be accommodated and their minimum total length.     

Cenp-F (mitosin) is more than a mitotic marker

Cenp-F (mitosin) is a large coiled-coil protein whose function has remained obscure since its identification a decade ago. It has been suggested that the protein plays a role in the kinetochore-mediated mitotic functions but until recently there was little evidence to support this postulation. Recent results from five laboratories have given insights on how Cenp-F may participate in the regulation of cell division. In this mini-review, we will summarize the current data regarding the mitotic tasks of Cenp-F as well as discuss how it is used as a proliferation marker of malignant cell growth in the clinic. Also, the protein’s post-translational modification by farnesylation and potential contribution to cell cycle effects of farnesyl transferase inhibitors will be addressed.     

Selective expression of nonsecreted triple-helical and secreted single-chain recombinant collagen fragments in the yeast Pichia pastoris

High-level recombinant expression systems for the production of stable triple-helical human collagens and collagen fragments have been developed in the yeast Pichia pastoris. Collagen fragments are secreted as single-chain polypeptides by the yeast alpha-mating factor pre-pro sequence, but secretion of full-length triple-helical procollagen molecules has not been achieved despite the use of the same secretory signal. We studied here the effects of the secretory signal and the conformation and size of the collagen polypeptide on its secretion in P. pastoris. Unlike the collagen signal sequence, the alpha-mating factor pre-pro sequence led to efficient secretion of single-chain 45 and 9 kDa type I collagen fragments. The efficiency was dependent on the length of the collagen polypeptide, as secretion of single-chain full-length 90 kDa alpha1(I) polypeptides was less efficient than that of the 45 kDa fragment. Furthermore, the conformation of the collagen polypeptides had a marked effect on secretion, as induction of trimerization of the 45 and 9 kDa fragments by either the C propeptide or the small trimerizing domain foldon led to an accumulation of triple-helical molecules inside the cells despite the presence of the alpha-mating factor pre-pro sequence. Our results show that P. pastoris is a suitable host for the development of tailored expression systems aimed at selective production of nonsecreted triple-helical and secreted single-chain collagen fragments of varying lengths for specific purposes.