Intramuscular 16-phenoxy PGE2 ester for pregnancy termination.

A new PGE2 derivative (16-phenoxy PGE2 methyl sulfonylamide sulprostone) was administered by the i.m. route to 48 women pregnancy in any of the three trimesters. The indications for pregnancy interruption were either serious medical problems in intact pregnancies (21 cases) or due to fetal death in utero (27 cases). Single doses of 500 micrograms were repeated every 4 hours in the former group or every 6 hours in the latter category for a maximum period of 24 hours. The treatment was successful in 81% of intact pregnancies and in 92.6% of fetal death cases with an overall mean induction interval of 12.9 hours. More than half the subjects did not experience any side effects apart from mild or moderate uterine colics. An overall mean of 1.4 episodes of vomiting or diarrhoea per induction trial was quite acceptable from the clinical point of view. The absence of serious complications in the group of critically sick women speaks in favor of the relative safety of the drug.     

Structural and evolutionary bioinformatics of the SPOUT superfamily of methyltransferases

Background  

SPOUT methyltransferases (MTases) are a large class of S-adenosyl-L-methionine-dependent enzymes that exhibit an unusual alpha/beta fold with a very deep topological knot. In 2001, when no crystal structures were available for any of these proteins, Anantharaman, Koonin, and Aravind identified homology between SpoU and TrmD MTases and defined the SPOUT superfamily. Since then, multiple crystal structures of knotted MTases have been solved and numerous new homologous sequences appeared in the databases. However, no comprehensive comparative analysis of these proteins has been carried out to classify them based on structural and evolutionary criteria and to guide functional predictions.     

A unique macrophage subpopulation signals directly to progenitor cells to promote regenerative neurogenesis in the zebrafish spinal cord

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Epidemiology and reporting characteristics of preclinical systematic reviews

In an effort to better utilize published evidence obtained from animal experiments, systematic reviews of preclinical studies are increasingly more common—along with the methods and tools to appraise them (e.g., SYstematic Review Center for Laboratory animal Experimentation [SYRCLE’s] risk of bias tool). We performed a cross-sectional study of a sample of recent preclinical systematic reviews (2015–2018) and examined a range of epidemiological characteristics and used a 46-item checklist to assess reporting details. We identified 442 reviews published across 43 countries in 23 different disease domains that used 26 animal species. Reporting of key details to ensure transparency and reproducibility was inconsistent across reviews and within article sections. Items were most completely reported in the title, introduction, and results sections of the reviews, while least reported in the methods and discussion sections. Less than half of reviews reported that a risk of bias assessment for internal and external validity was undertaken, and none reported methods for evaluating construct validity. Our results demonstrate that a considerable number of preclinical systematic reviews investigating diverse topics have been conducted; however, their quality of reporting is inconsistent. Our study provides the justification and evidence to inform the development of guidelines for conducting and reporting preclinical systematic reviews.

A cross sectional study of a sample of recent preclinical systematic reviews reveals deficiencies in reporting and provides the justification and evidence to inform the development of specific guidelines for conducting and reporting preclinical systematic reviews.     

SIGNALLING TO TRANSLATIONAL ACTIVATION OF TUMOUR NECROSIS FACTOR-α EXPRESSION IN HUMAN THP-1 CELLS

Monocytic THP-1 cells expressed tumour necrosis factor-α (TNF-α) mRNA, but hardly any detectable TNF-α protein and a partially activated MAP kinase ERK-2 in the unstimulated state. Stimulation with phorbol ester led to expression of TNF-α protein without significant changes in mRNA, a response that was sensitive to the MEK-1/2 inhibitors PD98059 and U0126. A calcium signal also led to expression of TNF-α protein, but now accompanied by a rapid increase in mRNA. A synergistic effect between phorbol ester and calcium ionophore was evident at the level of TNF-α protein, but not its mRNA. Stimulation with anisomycin led to a TNF-α expression that was sensitive to the p38 inhibitor SB203580. Actinomycin D lowered TNF-α mRNA in a similar way as PD98059 but was less inhibitory on PMA- or anisomycin-induced formation of TNF-α, thus confirming that these agents acted by causing translational derepression. Thus, in THP-1 cells MAP kinase pathways involving MEK-1/2 and possibly ERK-2 as well as the human p38 analogue were essential for basal TNF-α mRNA expression and translational activation.