Background: Children and young adults with JIA have increased levels of poor oral hygiene and dental decay [1].Periodontitis and types of arthritis are linked by similar components of blood cytokine profiles.Good dental health can be directly affected in JIA patients due to physical limitations in upper limb movements making brushing and flossing teeth difficult.An important factor in oral care is good dental hygiene and access to dental health practitioners.NHS advice is that all children should be reviewed by a dentist annually and be offered both sealant of their teeth and fluoride varnish at the appropriate time.Our aim was to establish if our patients had any barriers to accessing dental care.Methods: All patients (age 18 and under) diagnosed with JIA in the paediatric rheumatology clinic over a period of 3 months were asked to complete a dental care questionnaire.Parents completed the questionnaire for their children if necessary.Data were analysed using Excel.Results: 30 questionnaires were completed.Demographics were M:F 1:1.3, all children were diagnosed with JIA, average age 10.5 years with range 2-18.27 children were registered with an NHS dentist with the exception of one child with a private dentist.26 children had seen a dentist at least annually and one child in the past 2 years. 2 children, one aged 16, were not registered with a dentist because their parents didn't think it was important.11 children had 25 fillings in total, 9 of these children were not supervised during dental hygiene.13 children admitted to drinking sugary drinks daily and had 16 dental fillings.None of the children admitted to smoking.Conclusions: Whilst our audit showed that most children were registered with a dentist and were reviewed annually, only 1 child had been offered sealant and fluoride varnish.The NHS advises that children with chronic medical conditions can be seen either by their NHS dentist or by the local Community specialist dental service which can be accessed by referral from their rheumatology department or NHS dentist.None of the children were seen by the specialist dental service.We have developed an information leaflet informing parents and children with JIA of the importance of dental health explaining the benefits of both sealant and fluoride for teeth.
In the course of our 870um APEX/LABOCA follow up of the Herschel Lensing Survey we have detected a source in AS1063 (RXC J2248.7-4431), that has no counterparts in any of the Herschel PACS/SPIRE bands, it is a Herschel 'drop-out' with S_870/S_500>0.5. The 870um emission is extended and centered on the brightest cluster galaxy suggesting either a multiply imaged background source or substructure in the Sunyaev-Zel'dovich (SZ) increment due to inhomogeneities in the hot cluster gas of this merging cluster. We discuss both interpretations with emphasis on the putative lensed source. Based on the observed properties and on our lens model we find that this source could be the first SMG with a moderate far infrared luminosity (L_FIR 4. In deep HST observations we identified a multiply imaged z~6 source and we measured its spectroscopic redshift z=6.107 with VLT/FORS. This source could be associated with the putative SMG but it is most likely offset spatially by 10-30kpc and they could be interacting galaxies. With a FIR luminosity in the range [5-15]x10^{11} L_sol corresponding to a star formation rate in the range [80-260]M_sol/yr, this SMG would be more representative than the extreme starbursts usually detected at z>4. With a total magnification of ~25 it would open a unique window to the 'normal' dusty galaxies at the end of the epoch of reionization.
A novel series of DGAT-1 inhibitors was discovered from an oxadiazole amide high throughput screening (HTS) hit. Optimisation of potency and ligand lipophilicity efficiency (LLE) resulted in a carboxylic acid containing clinical candidate 53 (AZD3988), which demonstrated excellent DGAT-1 potency (0.6 nM), good pharmacokinetics and pre-clinical in vivo efficacy that could be rationalised through a PK/PD relationship.
Sulfur mustard (2,2‐dichlorodiethyl sulfide; HD), is a potent alkylating agent which in liquid or vapor form is capable of causing severe injuries to skin and respiratory tract, and was shown to cause short‐ and long‐term ocular injuries. N‐Acetylcysteine (NAC) may act as a mucolytic agent, changing the “wetting” and scavenging properties of the cornea and thus the adhesion of HD. Moreover, NAC is a scavenger of HD, an antioxidant and a glutathione precursor, which was shown to reduce HD toxicity in various systems. The ocular distribution of 14C, after topical application of liquid 14C‐sulfur mustard (14C‐HD) to the rabbit cornea, and the role of NAC in reducing HD retention and toxicity are presented in this study. Groups of rabbits were exposed to 0.4 µL of liquid 14C‐HD, placed at the center of the cornea, with or without NAC treatment. Fifty µL NAC (10% aqueous solution) was topically applied, 10 minutes before and 10 minutes after HD exposure. Three time points were evaluated: 1, 6, and 24 hr after HD exposure, six rabbits per time point. Evaluation consisted of clinical observation, measurement of biochemical parameters in aqueous humor (AQ), counting radioactivity concentration in ocular tissues, and histology of corneal sections. One hour after corneal exposure to liquid 14C‐HD, approximately 2% of total applied radioactivity was recovered. The highest 14C concentration was found in the cornea, followed by the tarsal section of eyelid, aqueous humor, nictitating membrane, and the frontal sclera (including conjunctiva). The rate of radioactivity decrease varied from one ocular tissue to the other, the highest rate was found in aqueous and vitreous humors, also in accordance with their higher turnover rates. The NAC treatment reduced the radioactivity in most ocular tissues. The HD exposure caused typical clinical and histological signs of HD intoxication, and increased the aqueous protein and prostaglandin (PGE) content. The NAC treatment lowered eyelid edema but had no effect on AQ protein or PGE content; however, there was some aggravating effect of the NAC treatment on corneal epithelial cells, seen at 1 and 6 hr after exposure.
We present Keck spectroscopy and UKIRT near-IR imaging observations of two 170\,h-selected sources from the {\it ISO}-FIRBACK survey which have faint counterparts in the optical, and $rK\sim5$. Both sources were expected to lie at $z>l$ based on their far-infrared, submillimeter and radio fluxes, assuming a similar spectral energy distribution to the local ultra-luminous infrared galaxy (ULIRG) Arp\,220. However, our spectroscopy indicates that the redshifts of these galaxies are $z<l$: $z=O.91$ for FN1-64 and $z=0.45$ for FN1-40. While the bolometric luminosities of both galaxies are similar to Arp\,220, it appears that the dust emission in these systems has a characteristic temperature of $\sim$30\,K, much cooler than the $\sim$SO\,K seen in Arp\,220. Neither optical spectrum shows evidence of AGN activity. If these galaxies are characteristic of the optically faint FIRBACK population, then evolutionary models of the far-infrared background must include a substantial population of cold, luminous galaxies. These galaxies provide an important intermediate comparison between the local luminous IR galaxies, and the high redshift submillimeter-selected galaxies, for which there is very little information available.
This text constitutes the proceedings of the 1st International Conference on the Chemistry of the Copper and Zinc Triads, held at the University of Edinburgh in July 1992. The conference identified three main themes - environmental chemistry, organometallic/co-ordination chemistry and biological/medicinal chemistry - under which the chemistries of the six elements concerned (Cu, Ag, Au, Zn, Cd and Hg) were discussed via keynote lectures, invited lectures, contributed lectures and posters. In broad terms, the text begins with papers concerned with biological and medicinal chemistry, moves through environmental aspects into co-ordination chemistry, then onto organometallic chemistry and cluster chemistry and finishes with a series of papers concerned with physicochemical studies of the six elements.
A convenient and rapid method of obtaining the cofactor of nitrogenase (FeMoco) with a low and apparently limiting Fe/Mo ratio has been developed. FeMoco can be extracted from the MoFe protein bound to DEAE-cellulose. The cofactor is eluted in either N-methylformamide (NMF), N,N-dimethylformamide (DMF), or mixtures of these solvents by use of salts such as Et4NBr,Bu4NBr,Ph4PCl, and Ph4AsCl. The method is simple, is rapid (45 min), yields concentrated cofactor, and, unlike the original method [Shah, V. K., & Brill, W. J. (1977) Proc. Natl. Acad. Sci. U.S.A. 74, 3249-3253] which requires anaerobic centrifugation, is easily scaled up. Furthermore, it gives yields of cofactor in excess of 70%. Its disadvantages are a high Fe:Mo ratio when DMF is the extracting solvent and a high salt concentration in the resultant FeMoco solution. These disadvantages are easily overcome by removing excess Fe by pretreating the cofactor with bipyridyl while still on the column. This gives Fe:Mo ratios of (6 +/- 1):1 (11 trials) with specific activities ranging from 170 to 220 nmol of C2H4/[min.(nmol of Mo)]. Chromatography on Sephadex LH-20 removes ca. 99% of the excess salt. The adsorption of MoFe protein to DEAE-cellulose seems to facilitate denaturation by organic solvents so that pretreatment of the protein with acid, used in earlier methods, is unnecessary. There is an apparent dependence on the charge density of the anion employed for elution of FeMoco bound to DEAE-cellulose, such that Cl- greater than Br- much greater than I-, PF6- is the order of effectiveness of the Bu4N+ salts of these anions.(ABSTRACT TRUNCATED AT 250 WORDS)
ChemInformVolume 18, Issue 9 Organoelement Compounds ChemInform Abstract: Kinetic, Spectroscopic, and Structural (Extended X-Ray Absorption Fine Structure) Studies on the Type 1 Blue Copper Protein Umecyanin. S. K. CHAPMAN, S. K. CHAPMAN Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorW. H. ORME-JOHNSON, W. H. ORME-JOHNSON Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorJ. MCGINNIS, J. MCGINNIS Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorJ. D. SINCLAIR-DAY, J. D. SINCLAIR-DAY Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorA. G. SYKES, A. G. SYKES Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorP.-I. OHLSSON, P.-I. OHLSSON Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorK.-G. PAUL, K.-G. PAUL Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this author S. K. CHAPMAN, S. K. CHAPMAN Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorW. H. ORME-JOHNSON, W. H. ORME-JOHNSON Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorJ. MCGINNIS, J. MCGINNIS Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorJ. D. SINCLAIR-DAY, J. D. SINCLAIR-DAY Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorA. G. SYKES, A. G. SYKES Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorP.-I. OHLSSON, P.-I. OHLSSON Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this authorK.-G. PAUL, K.-G. PAUL Dep. Inorg. Chem., Univ., Newcastle upon Tyne NE1 7RU, UKSearch for more papers by this author First published: March 3, 1987 https://doi.org/10.1002/chin.198709268Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue9March 3, 1987 RelatedInformation
The nature of the ligation of N-methylformamide (NMF) to the metal sites of FeMoco has been investigated. The IR spectrum of FeMoco in NMF shows an intense band at 1600 cm−1 which we assign to the v(CO) stretch of ligated NMF. This frequency is characteristic of N-deprotonated amide ligands, indicating that NMF ligation to FeMoco is predominantly through nitrogen. Hence NMF behaves as an anionic ligand. The importance of the amide functionality for FeMoco extraction has been further examined and a new extracting agent, 2-pyrrolidinone, has been employed. We hypothesize that, in the MoFe-protein, the primary coordination of the cofactor is via deprotonated backbone amide ligands.
The effects of pH variations on the visible spectrum (pKa 9.46 ± 0.04), e.s.r. spectrum, extended X-ray absorption fine structure (EXAFS), and on the reactivity of the blue copper protein umecyanin have been investigated. The electron-transfer reactions of umecyanin have been studied with the complexes [Co(dipic)2]–(dipic = dipicolinate) and [Co(C2O4)3]3– as oxidants for UCu(I), and [Ru(NH3)5(py)]2+(py = pyridine) as a reductant for UCu(II), at 25 °C, I= 0.10 M (NaCl). The oxidation of umecyanin with [Fe(CN)6]3– is extremely rapid, consequently a limited study was carried out at a lower temperature. The oxidation of the protein by [Co(phen)3]3+(phen = 1,10-phenanthroline) was also studied under these conditions for comparison. Of interest are the pKa values observed for the oxidation of umecyanin by [Co(C2O4)3]3–(pKa 9.68 ± 0.08) and the reduction of umecyanin by [Ru(NH3)5(py)]2+(pKa 9.50 ± 0.07). The low temperature (20 K)X-band e.s.r. spectrum of oxidised umecyanin (g‖= 2.32, g⊥= 2.06) shows little variation over the pH range 7.5–10.5. The Cu K-edge EXAFS of umecyanin in both oxidation states and at pH 7.5 and 10.5 were obtained. Analysis of data from the oxidised protein shows the Cu atom has two nitrogen ligands at 1.99 ± 0.03 Å and one sulphur at 2.13 ± 0.02 Å. In the reduced protein the bond lengths increase to 2.03 ± 0.03 Å and 2.21 ± 0.02 Å respectively. There was no detectable difference in co-ordination number or bond lengths at the different pH values, and no fourth ligand could be detected by the EXAFS technique. The results from these various studies are discussed in terms of changes at or near the active site of umecyanin.
Rate constants determined by the stopped-flow method for four protein-protein reactions at 25°C, pH's in the range 5.8–7.5. I = 0.10 M (NaCI), are as follows: cytochrome c(II) with plastocyanin, PCu(II). 1.5 × 106 M−1 sec−1, pH 7.6; high-potential iron-sulfur protein (Hipip) with PCu(II), 3.7 × 105 M−1sec−1. pH 5.8; cytochrome c(II) with azurin, ACu(ll). 6.4 × 103 M−1sec−1, pH 6.1; Hipip with ACu(II), 2.2 × 105 M−1sec−1, pH 5.8. Activation parameters have been determined for all four reactions; they indicate higher enthalpy requirements and less negative entropy requirements for the PCu(II) as opposed to ACu(II) reactions. Equilibrium constants K for association prior to electron transfer are < 150 M−1 for the cytochrome c(II) reduction of PCu(II) (estimated charges 8 + and 9-,respectively), and < 300 M−1 for the other reactions, indicating no favorable interactions. Rate constants have been analyzed in terms of the simple Marcus theory, which has previously given an excellent fit to thirteen protein-protein reactions considered by Wherland and Pecht. No similar correlation exists in the present studies, and calculated rate constants differ by orders of magnitude from experimentally determined values.