The mouse anti-morphine constipation test--a simple laboratory test of the gastrointestinal side-effect potential of orally administered prostaglandin analogues

A test is described which is simple, reliable and highly sensitive to the diarrhoea-inducing properties of orally administered prostaglandin analogues in mice. Comparison with human data shows similar orders of relative potency.     

The relaxant property of local prostaglandin E2 on the non-pregnant uterus — A cyclic triphasic response

The response of the non-pregnant human uterus to intravenous(i.v.) injections and intra-uterine instillation of various doses of prostaglandin E₂ (PGE₂) was evaluated at the different phases of the menstrual cycle in 13 fertile regularly menstruating woemn who were neither lactating nor using any hormonal therapy. Uterine contractility was recorded by the microballoon technique in at least three sessions(proliferative, mid-cycle and secretory) in a single cycle with endometrial biopsy performed immediately following the last session to ascertain that the particular cycle was an ovulatory one. Single i.v. injections of PGE₂ had a consistent stimulatory effect on the contractility throughout the cycle with a tendency towards a decreased uterine response at mid-cycle and luteal phase as compared to the proliferative part of the cycle. Intra-uterine instilation of the compound induced a peculiar and interesting type of response. In the proliferative and secretory phases of the cycle the response was one of stimulation ; being more pronounced in the former period. However, around ovulation time, the local administration induced an evident uterine relaxation in most cases without any instance of stimulation. The possible implication of this triphasic response behaviour of the non-pregnant uterus within certain physiological events and pathological conditions is discussed.     

Water hyacinth — A potential source of raw material for greaseproof paper

The potential use of water hyacinth as a pulp material for producing greaseproof paper was investigated. The proximate chemical analyses of the raw materials, the morphology of the water hyacinth stalk and fibre, pulp characteristics, and data on the physical properties of the paper hand-sheets formed from water hyacinth and bamboo pulps and their blends are presented. A comparative study of the pulp freeness (°SR) and drainage properties of water hyacinth and bamboo pulps showed that with a high freeness value of the pulps the drainage time increased. Blending of water hyacinth and bamboo pulps increased the physical strength. Paper hand-sheets made with a blend of water hyacinth pulp (75°SR) and bamboo pulp (80°SR), at 75:25 proportion, gave a tear index of 4·90 mN m² g⁻¹, tensile index of 51·10 N mg⁻¹ and burst index of 7·25 kPa m² g⁻¹. These were higher than the values obtained from sheets made with pulp blends (water hyacinth:bamboo) of 80:20 or 90:10. The pulp sheets at a blend proportion of 75:25 also gave satisfactory greaseproof properties.     

Properties of a partially-purified preparation of the prostaglandin —Forming oxygenase from sheep vesicular gland

The fatty acid oxygenase of sheep vesicular glands was solubilized with Tween-40 and purified 60-fold using ammonium sulfate precipitation and DEAE-cellulose chromatography. Glycerol (50%) stabilized the activity at all stages of purification and allowed long-term storage at −60°. The partially purified enzyme contained less than 0.7 nmoles of iron per mg of protein and less than 0.1 nmole of copper per mg of protein. Although the K_I values for aspirin, BL-2338, flurbiprofen and ibuprofen remained relatively unchanged during purification, the apparent K_I value for inhibition by indomethacin decreased from 120 to 2.7 μm.     

Effect of oestradiol — 17β and oxytocin treatment on prostaglandin F alpha release in the anoestrous ewe

The concentration of prostaglandin Fα in the vena caval blood at a point anterior to the entry of uterine venous blood was determined by radioimmunoassay in nine anoestrous ewes. At all times the concentrations were much greater than those in jugular blood. The ewes were given oestradiol-17β or oxytocin or oestradiol followed 24 hours later by oxytocin.Oxytocin alone had negligible effect on prostaglandin release. Oestradiol alone increased the concentration of prostaglandin in the posterior vena cava about threefold to 160 pg/ml. When oxytocin was given to oestrogen primed ewes the concentration in the posterior vena cava rose dramatically to 1000 pg/ml within 5 minutes after which it declined to pre-treatment values: repetition of oxytocin treatment in one hour was much less effective.     

The untapped potential of the GENSAT mice—A valuable resource for developmental biology

Gene Expression Nervous System Atlas (GENSAT) transgenic mice express EGFP, tdTomato, or Cre recombinase in a wide range of cell types. The mice and the bacterial artificial chromosome transgenes are available from repositories (MMRRC or CHORI), thereby making these resources readily available to the research community. This resource of 1,386 transgenic lines was developed and validated for neuroscience research. However, GENSAT mice have many potential applications in other contexts including studies of development outside of the CNS. The cell type‐specific expression of fluorescent proteins in these mice has been used to identify cells in living embryos, in living embryo explants, and in stem or progenitor cell populations in postnatal tissues. The large number of fluorescent protein driver lines generated by GENSAT greatly expands the range of cell type markers that can be used for live cell sorting. In addition, the GENSAT project has generated 278 new Cre driver lines. This review provides an overview of the GENSAT lines and information for identifying lines that may be useful for a particular application. I also provide a review of the few published cases in which GENSAT mice have been used for studies of embryonic development or analysis of stem/progenitor cells in nonneural tissues. genesis 54:245–256, 2016. © 2016 Wiley Periodicals, Inc.     

A comparison of prostaglandin F2α and three 16-aryloxy analogues on the isolated rabbit jejunum

Three 16-aryloxy analogues of PGF_2α are potent, full agonists on the isolated rabbit jejunum. Their actions are more prolonged than that of PGF_2α, and radioactive tracer studies with one of the analogues reveal a slower wash-out of the analogue compared to PGF_2α, under superfusion conditions. During the prolonged contractile response diminished responses to PGF_2α were obtained: this effect was investigated in terms of receptor desensitization. The actions of these analogues were also investigated on the isolated guinea-pig ileum and the rabbit oviduct .     

Synthesis of cyclooctapeptides: constraints analogues of the peptidic neurotoxin, ω‐agatoxine IVB—an experimental point of view

ω‐AGA IVB is an important lead structure when considering the design of effectors of glutamate release inducting P/Q‐type calcium channels. The best route to achieve the analogues possessing the three‐dimensional arrangement corresponding to the native binding loop was the introduction of constraint by ring formation via side chain to side chain lactamization for suitably protected Lys and Glu residues. Since tryptophane residue located at position 14 of this neuropeptide has been suggested as essential for binding, analogues in which this amino acid was replaced by aza‐tryptophane and alanine were synthesized. The synthesis was carried out on various acid‐labile resins (BARLOS chlorotrityl, Rink amide, PEG‐based or Wang resins), by Fmoc strategy. In this paper, we describe optimization of the peptide cyclization with various protecting groups, and on resin or in solution cyclization experimental parameters. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.     

Evolution of the Reproductive Mechanisms in Tardigrades — A Review

Although tardigrades can reproduce only through gametes they have exploited several modes of reproduction, which may be determined by their environment. Marine species (mainly heterotardigrades) are gonochoristic; hermaphroditism is only cited once, and parthenogenesis is unknown. In many cases females mature one egg at a time throughout adult life, whereas males are semelparous. Gonochorism is still present in limno-terrestrial species, while sporadic hermaphroditism occurs in several eutardigrade families. Thelytoky is the most common mode of reproduction in non-marine Tardigrada. Females are iteroparous, laying groups of eggs (free or in the exuvium), while males are semelparous (in a limnic species) or iteroparous with a continuous or cyclical maturation of the spermatozoa (in species from moss and leaf litter). Self-fertilisation appears to characterise hermaphroditic species, found in freshwater, mosses, leaf litter and soil. Egg maturation in these species is similar to that of the gonochoristic species, while spermatozoa mature in appreciable numbers before the oocytes, subsequently maturing continuously but in small numbers over the life of the animal. Parthenogenesis in limno-terrestrial tardigrades always appears continuous. In many species only females occur, but morpho-species populations may be found with both bisexual amphimictic (diploid) and unisexual thelytokous (often but not always polyploid) cytotypes. We can hypothesise that with the evolution of cryptobiosis and passive dispersal unstable and isolated habitats may favour parthenogenesis and self-fertilisation, as both reproductive modes allow colonisation of a new territory by a single individual. Parthenogenesis and hermaphroditism do not occur in the same species, and we can surmise that self-fertilisation will only evolve where parthenogenesis has never occurred.     

The elementary RNP fiber — not the higher order structure — determines the all-or-none disintegration behaviour of balbiani ring pre-messenger RNP particles upon RNase A treatment

Summary— Balbiani ring premessenger ribonucleoprotein (RNP) particles are built from a 7-nm RNP fiber which is tightly folded into a ring-shaped RNP ribbon. Isolated particles are known to disintegrate in an all-or-none fashion upon RNase A treatment. In the present study we investigated whether this mode of disintegration is dependent on an intact particle structure or is inherent in the 7-nm fiber. When treated at low ionic strength, the Balbiani ring (BR) particles lost their higher order structure and the 7-nm fiber was unpacked, as evidenced by sucrose gradient sedimentation and electron microscopy. When treated with RNase A, unfolded as well as intact particles disintegrated in the all-or-none fashion, with similar kinetics and without apparent intermediates. Proteinase K treatment, however, obliterated this pattern: the protein-free particle RNA degraded progressively. As the typical disintegration pattern of the particles was not altered by unfolding, but was lost by deproteinization, the all-or-none mode of disintegration is likely to be a property of the 7-nm RNP fiber.     

The stability of cylindrin β‐barrel amyloid oligomer models—A molecular dynamics study

Small‐soluble amyloid oligomers are believed to play a significant role in the pathology of amyloid diseases. Recently, the atomic structure of a toxic oligomer formed by an 11 residue and its tandem repeat was found to have an out‐off register antiparallel β‐strands in the shape of a β‐barrel. In the present article we investigate the effect of mutations in the hydrophobic cores on the structure and dynamic of the β‐barrels using all atom multiple molecular dynamics simulations with an explicit solvent. Extending previous experiments with molecular dynamics simulations we systematically test how stability and formation of cylindrin depends on the interplay between hydrophobicity and steric effects of the core residues. We find that strong hydrophobic interactions between geometrically fitting residues keep the strands (both in register and out‐off‐register interface) in close proximity, which in turn stabilizes the side‐chain and main‐chain hydrogen bonds, and the salt bridges on the outer surface along the weak out‐of‐register interface. Our simulations also indicate presence of water molecules in the hydrophobic interior of the cylindrin β‐barrel.Proteins 2013. © 2013 Wiley Periodicals, Inc.     

Inhibition by prostaglandin E2 of neurotransmission in rabbit but not human bronchus — A calcium-related mechanism?

Prostaglandins have been implicated in the development of airway hyperresponsiveness, and this may be mediated via modulation of neurotransmission. We compared the effects of prostaglandin E₂ on the contractile response to electrical field stimulation in rabbit and human bronchus. Prostaglandin E₂ produced marked inhibition in rabbit bronchus (mean % inhibition 35±17, P< 0.05) but was without effect in human bronchus. The inhibition in rabbit bronchus was not the result of a direct effect on muscle tone and the site of action is likely to be pre-synaptic since prostaglandin E₂ had only minor effects on exogenous acetylcholine. Since prostaglandins are known to affect calcium mobilization, we compared the dependence of cholinergic stimulation on the calcium voltage dependent channel (VDC) in the two species. Cholinergic stimulation was dependent on the VDC in rabbit but not human bronchus and this may be an explanation for the different effects of prostaglandin E₂ in the two species.     

A simple plate test for screening colicine-inducing substances as a tool for the detection of potential carcinogens.

A simple and rapid plate test is described for screening substances that induce colicine E2. By using chemicals activated with microsomal enzymes and a permeable (rfa) tester bacterium that is also deficient in DNA repair (uvrB), the range of inducing substances that can be detected has been extended. The possible correlation between colicine-inducing substances and carcinogens is discussed.     

The genetic toxicity of 3,3′,4,4′-tetrachloroazobenzene and 3,3′,4,4′-tetrachloroazoxybenzene: discordance between acute mouse bone marrow and subchronic mouse peripheral blood micronucleus test results

3,3′,4,4′-Tetrachloroazobenzene (TCAB) and 3,3′,4,4′-tetrachloroazoxybenzene (TCAOB) are dioxin-like chemicals that were investigated for toxicity in 13-week gavage studies in male and female B6C3F₁ mice and F344N rats by the National Toxicology Program. As part of the comprehensive toxicological investigation of these chemicals, peripheral blood smears from mice treated 5 days per week for 13 weeks with 0.1–30 mg/kg/day TCAB or TCAOB were analyzed for the frequency of micronucleated (MN) normochromatic erythrocytes (NCE). Both chemicals produced significant increases in MN-NCE in male and female mice. In contrast to these positive results in subchronic exposure studies, no significant increases were seen in acute bone marrow MN tests in male mice administered three daily injections of 50–200 mg/kg/day TCAB and TCAOB. The results with TCAB and TCAOB suggest that the routine integration of MN tests with subchronic toxicity studies may allow detection of mutagenic activity for some chemicals that fail to elicit responses in short-term, high dose tests. In addition, the integration of mutagenicity tests into general toxicity tests reduces the use of laboratory animals and the cost of the testing.     

Role of hypoxia‐inducible factor 1α as a potential biomarker for renal diseases—A systematic review

Renal cells need oxygen for homeostasis; it is known for adjusting cellular functioning and the energy obtainment have a broad relationship with cellular respiration, through the O₂ bioavailability. O₂ homeostasis regulation in the kidney is mediated by hypoxia‐inducible factors (HIFs). HIF is divided into three α isoforms, represented by HIF‐1α, HIF‐2α, and HIF‐3α in addition to three paralogs of HIF‐1β; these are involved in some metabolic processes, as well as in the pathogenesis of several diseases. Renal biopsy analyses of patients and experimental animal models aim to understand the relationship between HIF and protection against developing renal diseases or the induction of their onset, being thus this molecule can be considered a potential biomarker of renal disease. We carried out a systematic review to which we included studies on HIF‐1α and renal disease in the last 5 years (2013‐2018) in researches with humans and/or animal model through searches in three databases: LILACS, PubMed, and SciELO by two researchers. We obtained 22 articles that discussed the relationship with HIF as inductor or protector against renal disease and no relation between HIF and renal. We observed controversies remain regarding the relation between of HIF with renal diseases; this may be related to the different intracellular pathways mediated by HIF‐1α, thereby determining differentiated cellular responses.     

The potential use of atomic force microscopy for studying corrosion of metals in the presence of bacterial biofilms — an overview

This communication outlines the principles of application of scanning probe microscopy (SPM) as a tool for studying physico-chemical and biological phenomena and discusses the potential use of atomic force microscopy (AFM) , a form of SPM, for investigation of bacterial biofilms formed on metal surfaces and for studying corrosion of these surfaces in the presence of such biofilms. AFM images showing biofilms developed in pure cultures of either Pseudomonas species on copper, or by a marine isolate of sulphate-reducing bacterium on 304 stainless steel are presented to demonstrate usefulness of the SPM technique for both quantitative and qualitative determination of biocorrosion.