Oxytocin and cholecystokinin secretion in women with colectomy

BACKGROUND: Cholecystokinin (CCK) concentrations in plasma have been shown to be significantly higher in colectomised subjects compared to healthy controls. This has been ascribed to reduced inhibition of CCK release from colon. In an earlier study CCK in all but one woman who was colectomised, induced release of oxytocin, a peptide present throughout the gastrointestinal (GI) tract. The aim of this study was thus to examine if colectomised women had a different oxytocin response to CCK compared to healthy controls. METHODS: Eleven women, mean age 34.4 ± 2.3 years, who had undergone colectomy because of ulcerative colitis or constipation were studied. Eleven age-matched healthy women served as controls. All subjects were fasted overnight and given 0.2 μg/kg body weight of CCK-8 i.v. in the morning. Samples were taken ten minutes and immediately before the injection, and 10, 20, 30, 45, 60, 90 and 120 min afterwards. Plasma was collected for measurement of CCK and oxytocin concentrations. RESULTS: The basal oxytocin and CCK concentrations in plasma were similar in the two groups. Intravenous injection of CCK increased the release of oxytocin from 1.31 ± 0.12 and 1.64 ± 0.19 pmol/l to 2.82 ± 0.35 and 3.26 ± 0.50 pmol/l in controls and colectomised women, respectively (p < 0.001). Given the short half-life of CCK-8 in plasma, the increased concentration following injection could not be demonstrated in the controls. On the other hand, in colectomised women, an increase of CCK in plasma was observed for up to 20 minutes after the injection, concentrations increasing from 1.00 ± 0.21 to a maximum of 1.81 ± 0.26 pmol/l (p < 0.002). CONCLUSION: CCK stimulates the release of oxytocin in women. There is no difference in plasma concentrations between colectomised and controls. However, colectomy seems to reduce the metabolic clearance of CCK. The hyperCCKemia in patients who had undergone colectomy is consequently not only dependent on CCK release, but may also depend on reduced clearance

Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5′-GTgG-3′ sequence: destabilization of two base pairs at the lesion site

The 5R thymine glycol (5R-Tg) DNA lesion exists as a mixture of cis-(5R,6S) and trans-(5R,6R) epimers; these modulate base excision repair. We examine the 7:3 cis-(5R,6S):trans-(5R,6R) mixture of epimers paired opposite adenine in the 5′-GTgG-3′ sequence with regard to nucleotide excision repair. Human XPA recognizes the lesion comparably to the C8-dG acetylaminoflourene (AAF) adduct, whereas XPC/HR23B recognition of Tg is superior. 5R-Tg is processed by the Escherichia coli UvrA and UvrABC proteins less efficiently than the C8-dG AAF adduct. For the cis-(5R, 6S) epimer Tg and A are inserted into the helix, remaining in the Watson–Crick alignment. The Tg N3H imine and A N6 amine protons undergo increased solvent exchange. Stacking between Tg and the 3′-neighbor G•C base pair is disrupted. The solvent accessible surface and T2 relaxation of Tg increases. Molecular dynamics calculations predict that the axial conformation of the Tg CH3 group is favored; propeller twisting of the Tg•A pair and hydrogen bonding between Tg OH6 and the N7 atom of the 3′-neighbor guanine alleviate steric clash with the 5′-neighbor base pair. Tg also destabilizes the 5′-neighbor G•C base pair. This may facilitate flipping both base pairs from the helix, enabling XPC/HR23B recognition prior to recruitment of XPA

Structures of (5′S)-8,5′-Cyclo-2′-deoxyguanosine Mismatched with dA or dT

pubs.acs.org/cr

Using persona as lenses for a reference model

This paper investigates the value of persona in relation to a conceptual product: the ENVRI reference model designed for environmental research infrastructures. Three personas have been created to understand the use of the model and the challenges faced when applying it. Personas helped identify the level of support required by different users, prioritise the audience to address first, and revealed what aspects of the model are important to different audiences. We have made significant progress in understanding how to improve communication about the model to each persona

Theoretical analysis of DNA intrastrand cross linking by formation of 8,5'-cyclodeoxyadenosine.

Formation of intramolecular cross links by addition of C(5') deoxyribose radicals to the C(8)-N(7) double bond of an attached adenine base was analyzed by ab initio quantum-chemical methods. Conformational preferences that influence the stereospecificity of the reaction were investigated. A good correlation was found between the ratio of experimental yields of R and S stereoisomers of 8,5'-cyclodeoxyadenosine and the relative energy of conformations of the C(5') radical that are precursors to these isomers. Molecular mechanics based on the AMBER force field was used to model the effect of 8,5'-cyclodeoxyadenosine on the conformation of the DNA dodecamer d(CGCGAATTCGCG)2 with the lesion at the A6 position. The R and S stereoisomers of the intrastrand cross link cause comparable levels of DNA distortion with the major conformational changes occurring in backbone torsional angles at the site of the lesion

Distribution of ions around thymine dimer containing DNA: A possible recognition element for endonuclease V

The molecular link between sunlight exposure and skin cancer can be traced to the formation of cyclobutane pyrimidine dimers together with (6-4) photoadducts of pyrimidines in DNA upon exposure to UV radiation. The mutagenicity of these lesions is frequently explained by miscoding during DNA replication due to perturbations of base-pairing interactions. However the mutagenicity of UV photoproducts depends of their sequence context, suggesting that more global structural changes in DNA contribute to mutation induction. One of the most effective protections against the deleterious effects of cyclobutane pyrimidine dimers is the wide range of repair of this lesion by different enzymatic pathways. This paper presents the results of a 200 ps molecular dynamics simulation on the dodecarner d(CGCGAATTCGCG){sub 2} containing a cis, syn-cyclobutane thymine dimer, explicit water and counterions. The averaged structure calculated from the simulation shows good agreement with the available NMR data. The distribution of counterions around the damaged DNA is different from that around a non damaged DNA and suggests a possible mechanism of damage recognition by the enzyme